The Psychiatry of Palliative Medicine

The Psychiatry of
The Psychiatry of Palliative Medicine

Palliative Medicine
  
Second Edition
This Second Edition of The Psychiatry of Palliative Medicine remains a practical and
pragmatic distillation of the psychiatry relevant to the terminally ill. Revised throughout
and greatly expanded by the addition of two entirely new chapters, it reviews the major
psychiatric syndromes encountered in palliative care – depression, anxiety, delirium
– and examines psychopharmacological and psychological interventions in detail. It
succinctly considers the psychiatric aspects of pain, sleep, cognitive impairment, terminal
The Psychiatry of
Palliative Medicine
neurodegenerative diseases, sedation, artificial feeding and euthanasia. The dying,
chronically ill psychiatric patient is also discussed.
The author has drawn on his great experience in both consultation–liaison psychiatry
and palliative medicine to produce an essential, evidence-based guide for all healthcare
professionals involved in palliative care. These include consultants and senior nurses, as
well as psychiatrists, especially consultation–liaison psychiatrists, and trainees.
  
‘I find this an immensely sympathetic book, beautifully written. It is a testimony to the Second Edition
  

summation of specialist psychiatric knowledge, broad scholarship and a rich personal practice
in bedside palliation.’ From the Foreword by Ian Maddocks
AD (Sandy) Macleod
    
‘...a relevant, highly readable and reasonably priced book which will be of interest to all,
whether from a psychiatric or palliative care background, who seek to improve the care of
dying patients.’    
International Psychogeriatrics
‘Practical, scientifically based and scholarly, addressing a comprehensive set of common and
Second Edition AD (Sandy) Macleod

important clinical problems in palliative care. The book will doubtlessly be highly valued
by palliative care clinicians for its practical and thorough overview of some of the most
challenging clinical problems they face. Excellent and timely.’
Australian and New Zealand Journal of Psychiatry
    

Counselling for Death and Dying Practical Psychiatry of Old Age
Person-centred dialogues Fourth Edition
Richard Bryant-Jefferies John P Wattis and Stephen Curran
ISBN 978-1-84619-535-8
www.radcliffepublishing.com
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The Psychiatry of
Palliative Medicine
THE DYING MIND
SECOND EDITION
AD (SANDY) MACLEOD
MBChB, FRANZCP, FAChPM
Medical Director
Nurse Maude Hospice, Christchurch, New Zealand
Consultant Psychiatrist
Burwood Hospital, Christchurch, New Zealand
Adjunct Associate Professor
Health Sciences Department, University of Canterbury, New Zealand
Foreword by
IAN MADDOCKS
Emeritus Professor of Palliative Care
Flinders University of South Australia
Radcliffe Publishing
London • New York
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2011 by Sandy Macleod

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Contents
Foreword to the second edition vi

Preface to the second edition viii
About the author ix
Contributor x
1 Psychiatry and palliative medicine 1

2 Adjustment and anxiety 5
3 Psychological issues and dying 23
4 Families and caregivers 39
5 Psychiatry, spirituality and palliative medicine 51
Simon Dein
6 Pain and psychiatry 59
7 Other symptoms and the psyche 85
8 Depression 93
9 Delirium 117
10 Sleep, sedation and coma 139
11 Neoplasms 157
12 Cognitive dysfunction and dementia 173
13 Terminal neurological disorders 187
14 Chronic mental illness and dying 199
15 Euthanasia and psychiatry 209
16 Psychopharmacology 231
Foreword to the second edition
The need for Palliative Medicine to support specialties other than oncology is
being increasingly recognised, finding expression in articles and monographs
relating to the advanced stages of cardiac, respiratory and neurological diseases,
and resulting in a new range of referrals. Referrals from psychiatry for palliative
assistance are few, since that field of disease management less often involves
predicable imminent death, but, conversely, a partnership with psychiatry is
a significant benefit to palliative medicine. Major discomfort coupled with an
imminence of death challenges the mental and spiritual well-being of affected
individuals and their families. Professor Sandy Macleod’s book, sub-titled The
Dying Mind (a title I prefer), has deservedly been well received, and it is time for
an update with some appropriate revisions.
Because few psychiatrists have shown interest in this field, the task of working
with the mental and spiritual discomforts of the dying mind depends on staff
with limited training in behavioural medicine and psychiatry. The first edition
of this text showed how a pragmatic knowledge of the psychiatric approach and
management options can make a difference. The sensible guidance it offered
has enabled palliative care staff to serve their client patients and families more
adequately. A clear didactic style continues here, and the aphorisms I enjoyed
so much the first time round remain: ‘physical examination of the terminally ill
is predominantly a psychological exercise’; ‘psychologically healthy persons do
their own psychotherapy’; and ‘the nurse is a powerful analgesic’.
A new one is: ‘A normal family does not exist’, and this leads into a chapter on
the tasks and the risks of bringing care to those with whom the patient is close.
Dying is an intense and important time, affecting the dynamic of the family in
major ways. The carer can become ‘the hidden patient’. Staff, also, can become
very involved in their caring role, and risk being idealised by their patients,
but the message here is that ‘burn-out’ has more to do with management and
team hygiene than daily contact with dying persons. Concern for the welfare of
family members often needs to extend beyond the time of death, and Macleod
emphasises the burden of loss: ‘Our losses are never irretrievably forgotten.
Grief is never fully resolved’. Neither an over-pathologising of bereavement nor
discounting it are appropriate.
Another new chapter concerns psychotropic medication essential for palliative
vi
FOREWORD TO THE SECOND EDITION vii
care. Formularies in most countries now offer extensive options for prescribing
opioids, antidepressants, anxiolytics and antipsychotics. Many practitioners
will have their own list of favourites, but Professor Macleod offers suggestions,
highlighting the need for a basic formulary that avoids the risk of adding one
drug on another when discomforts persist. And there are more of the useful,
simple suggestions that speak of the author as an experienced bedside clinician:
‘Swallow the capsule with the head held forward’.
Concern for the soul was a major incentive for the establishment of the first
hospices by religious foundations. Its secular equivalent for the modern era –
specialist psychiatric care – does not often reach into ‘the spiritual’, and the cure
of souls is pursued with less confidence these days, even by our clergy. For this
edition, Professor Macleod has asked Dr Simon Dein to approach the topic of
spirituality in the secular setting. He affirms the importance of staff being pre-
pared to enter into exchanges with their patients that allow exploration of belief,
hope and religious practice, and urges them to assume a greater confidence. The
interaction of the spiritual unease with mental or physical distress is undoubted,
and spiritual pain will not respond promptly to opioids. Spirituality is not the
same as religiosity, and this is an area too important to be left to the visiting
clergy, though many clergy, through sensitivity and experience, will prove valu-
able members of the palliative team.
The discussion on euthanasia is now expanded with reference to the recent
experiences of those states where physician assistance to die has been author-
ised with various cautions and constraints. The involvement of the psychiatrist
will not solve the thorny issues of futility, competence, depression and fear that
accompany requests for euthanasia, but it has something to offer beyond the
enthusiastic participation of lawyers. Macleod concludes with a sage warning:
‘The euthanasia issue will not vanish from modern society. Medicine and psy-
chiatry need to start contributing to the debate rather than merely dismissing
euthanasia as wrong’.
I conclude as I did in introducing the first edition. We who practice palliative
medicine rarely can restore to our patients the comfort, dignity and function to
which they aspire. Do they lose hope? Embedded in Macleod’s term ‘covenant of
acceptance’ is the offer of a realistic hope, one in which staff, family and patient
may all conspire. I find this an immensely sympathetic book, beautifully written.
It is a testimony to the summation of specialist psychiatric knowledge, broad
scholarship and a rich personal practice in bedside palliation.
Ian Maddocks
Emeritus Professor of Palliative Care
Flinders University of South Australia
March 2011
Preface to the second edition
This is a book for clinicians, written by a clinician practising both psychiatry

and palliative medicine. I hope it may better inform medical and nursing prac-
titioners about the psychiatry of relevance to the terminally ill. The clinical focus
of this book is palliative rather than supportive care. It concerns managing the
terminal phase of life. It is a distillation of clinical knowledge, observation and
experience, the current medical literature (evidence based where available) and
the opinions and biases of the author. Brevity necessitates incomplete considera-
tion of all aspects of the subject. I have therefore concentrated upon those clinical
predicaments that frequently demand a pragmatic knowledge of psychiatry. It
will not be appreciated by all; however, highlighted are some clinical issues and
concepts of management that to date have been rather ignored by palliative
medicine.
Sandy Macleod
March 2011
ad.macleod@cdhb.govt.nz
viii
About the author
Associate Professor Sandy Macleod graduated from the University of Otago

in 1974. After several years as a general practice locum in New Zealand and the
UK, Dr Macleod completed his specialist training in psychiatry in Dunedin,
New Zealand. Periods of study in Oklahoma City, Boston and London followed.
Since 1985 Dr Macleod has worked as a consultation–liaison psychiatrist/
neuropsychiatrist at Christchurch and Burwood Hospitals, Christchurch, New
Zealand. In 1993, during tenure as visiting psychiatrist to Burwood Hospice,
the illness of the medical officer and the persuasion of the nursing staff enticed
Dr Macleod to commence an additional career in palliative care. Juggling busy
clinical practices in neuropsychiatry and palliative medicine is demanding and
challenging. The pleasures of being able to practise psychiatry within medicine
have been immense. Dr Macleod is an adjunct associate professor in the Health
Sciences Department at the University of Canterbury.
The co-author of a popular regional palliative care handbook, Dr Macleod has
also published over 50 articles, chapters and letters about clinical and historical
topics in psychiatry and palliative medicine.
ix
Contributor
Simon Dein
Senior Lecturer in Anthropology and Medicine, University College, London
Honorary Consultant Psychiatrist, Princess Alexandra Hospital, Harlow, Essex
Honorary Consultant Palliative Medicine, St Clare Hospice, Hastingwood, Essex
x
CHAPTER 1
Psychiatry and palliative medicine
It is the special vocation of the doctor to grow familiar with suffering.
John Greenleaf Whittier (1807–92)1
The cardinal goal of medical care is to alleviate suffering. Suffering is an unpleas-

ant and distressing emotional experience that undermines quality of life.2 When
illness confronts the integrity of how we define ourselves, of how we function,
of what roles we perform, and how we perceive ourselves, suffering eventu-
ates. The individual’s personhood is threatened by an event such as disease.3
Illness erodes ‘the self ’, and suffering is the symptom of this damage. Suffering
encompasses physical, psychological, spiritual and philosophical aspects of the
person. Medicine does not have armamentarium to address all the components
of suffering induced by disease. Suffering in advanced cancer patients cannot be
eliminated, but if adequate relief is achieved then coping and personal growth
can occur.4 Multidisciplinary healthcare teams are necessary to tackle this chal-
lenge. Modern medicine, preoccupied by curing rather than caring, focuses on
biology rather than psychology and sociology. The fragmentation of medicine,
made inevitable by the huge clinical and scientific knowledge base, distracts from
the commonalities between the various specialties and subspecialties. Psychiatry
and palliative medicine attend patients who are mentally distressed and dying.
Neither condition is easily amenable to biomedical interventions. These ‘old-
fashioned’ medical specialties practise biopsychosocial medicine with as much
artistry as science. The clinical outcome in psychiatry is ‘good’ palliation of
mental distress. In palliative medicine it is a ‘good death’. The diseases of neither
patient group are curable. The best that can be achieved is symptom control and
maintenance of that control. Quality of (remaining) life is thereby improved and
some suffering relieved.
Dame Cicely Saunders – the founder of the modern hospice movement –
envisioned a field that would encompass the physical, psychological and spiritual
1
2 THE PSYCHIATRY OF PALLIATIVE MEDICINE
dimensions of care. In its earlier years the movement was exquisitely focused
on the physical aspects of symptom management, though there are indications
that this is beginning to change towards a more holistic approach.5 Many of the
distressing symptoms experienced in the ‘deathbed’ are not exclusively physical.
Some are primarily psychological or psychiatric, and some are psychosomatic
or ‘somato-psychic’. Formalising ‘distress’ as the ‘sixth vital sign’ in the assess-
ment of cancer patients may encourage an improved clinical appreciation of the
importance of the mind of the sick.6 As John Donne (1572–1631) commented,
‘That which destroies body and soul, is in neither, but in both together’.7
Terminally ill patients can develop psychiatric illness. The provision of spe-
cialist psychiatric care to the dying is sporadic and inadequate. Psychiatrists
rarely venture off their patch and into palliative care facilities. Despite the interest
and want of a few psychiatrists, this situation is unlikely to change. There are few
psychiatrists interested, trained, and practising both subspecialities. However,
according to Susan Block, professor of psychiatry at Harvard Medical School,
‘there are a lot of frustrated humanists (in psychiatry) who are getting pushed
into just doing psycho-pharmacology, but who really care about the patient’s
existential issues’. 8 But funding psychiatrists to work in palliative care can be a
difficult prospect, despite the obvious need and the opportunities for collabora-
tion. Some fortunate patients are seen through consultation–liaison psychiatric
services to general hospitals. Finlay correctly points out the variability of the
provision of consultation–liaison services throughout the UK.9 The decline of
consultation–liaison psychiatric services worldwide over the last two decades,
because neither mental health nor medical services are willing to fund these
services despite being appreciated and effective, makes the reality of better access
to psychiatry unlikely. A ‘solution’ is that of enhancing the psychiatric skills of
palliative care practitioners and fostering the partnership. In the foundation
period of modern palliative medicine the deficits identified were those of ‘com-
munication skills’. More recently, depression, the psychosocial aspects of pain,
and delirium have been areas of educational endeavour. The claiming of pallia-
tive medicine by physicians’ colleges, and the narrow base of specialist medicine
training, has resulted in very limited exposure to psychiatry by prospective pal-
liative medicine specialists. Palliative care nurses usually possess considerable
experience and intuitive skill in dealing with disturbed patients, but lack a sound
psychiatric knowledge base. As palliative care is slowly expanding outside its tra-
ditional oncology base into neurological, cardiovascular, renal and many other
areas, there is a need to extend expert knowledge. These challenges rely upon a
working familiarity with mental illness and with its management.
The fundamental clinical skill of medicine is acquiring the history of the ill-
ness from the patient. The patient is the one suffering, they know their symptoms
and the doctor’s task is to extract this knowledge and expertly interpret it. The
PSYCHIATRY AND PALLIATIVE MEDICINE 3
history provides the information on which diagnostic hypotheses are formulated.

The definitive diagnosis is determined from the differential diagnoses with the
assistance of objective information provided by the clinical examination and
the investigations. Acquiring a psychiatric history is little different to any other
medical history. Providing the patient with the opportunity to describe their
symptoms, to reveal their narrative, is the key to good history taking. The inter-
rogative pronoun that ensures a description of ill health is ‘how’. ‘How is your
health affecting you?’, ‘How are you feeling?’, ‘How do you toilet?’, followed by
repeated requests to further describe and elaborate, provides copious informa-
tion, and more efficiently than with closed questions. Allowing the patient the
first half to two-thirds of the interview time for this is appropriate and efficient.
The doctor assumes control for the final portion in order to further clarify any
details and ask specifically about medications, allergies and personal habits. This
interview format applies equally to a full 50-minute psychiatric assessment and a
10-minute general practice consultation. Terminally ill patients are certainly not
an exception. Their symptom load and appreciation of the preciousness of time
encourages productive history taking in a brief period. Often 10–15 minutes
is sufficient. Specific questions need to be asked of the terminally ill concern-
ing fatigue, hallucinations and suicide risk, for these symptoms tend not to be
volunteered.
What constitutes an adequate mental status examination in the dying should
be influenced by what the examiner hopes to confirm. Delirium, depression,
anxiety and cognitive dysfunctions are the common mental health problems of
the dying. Time is limited, for energy and ability to cooperate are compromised.
The bare essentials of a mental status examination in a terminally ill patient
should include estimates of consciousness, orientation, recent memory, simple
calculation and mood. Physical examination of the terminally ill is predomi-
nantly a psychological exercise. While academically it is gratifying to confirm
the historical impression of an enlarged liver or bronchopneumonia, rarely
does this influence a management plan. Most persons have a belief that medical
examination, rather than history, is the key to medical practice. Until physically
examined, even if the examination is only cursory, most don’t consider they
have been properly assessed. The stethoscope and the percussion hammer are
powerful tools of comfort. This is not to suggest that a medical examination
doesn’t provide useful confirmatory information, including for mental illness.
The traditional medical history and examination is a better assessment tool than
the multitude of scales and psychometric measures available.
The practice of clinical psychiatry and medicine in general, requires knowl-
edge of psychology. Personality traits, coping skills, general intellectual function
and current stressors impact upon adjustment to, and living with, termi-
nal illness. Modern psychology is cognitive and behavioural in philosophy.
Psychodynamic conceptualisation is less emphasised. There is a considerable

literature concerning psychology and severe illness. The psychiatric literature is
less robust. The discipline of psychiatry encompasses both organic and psycho-
logical dysfunction. The vast majority endure a sad and unfortunate terminal
illness with courage and stoicism. They manage ‘normally’. For them, psychiatry
has nothing to offer. For those with dual pathology, good psychiatry and good
palliative medicine can enhance the quality of remaining life.
REFERENCES
1 Whittier JG. Quoted in: Strauss MB, editor. Familiar Medical Quotations. Boston: Little,
Brown & Company; 1968. p. 578.
2 Cherny NI, Coyle N, Foley KM. Suffering in the advanced cancer patient: a definition
and taxonomy. J Palliat Care. 1994; 10: 57–70.
3 Cassel EJ. The nature of suffering and the goals of medicine. N Engl J Med. 1982; 306:
639–45.
4 Cherny NI. The treatment of suffering in patients with advanced cancer. In: Cochinov
HM, Breitbart W, editors. Handbook of Psychiatry in Palliative Medicine. Oxford:
Oxford University Press; 2000. pp. 375–96.
5 Chochinov HM. Psychiatry and palliative care: 2 sides of the same coin. Canad J
Psychiatry. 2008; 53: 711–12.
6 Chaturvedi S, Venkateswaran C. New research in psychooncology. Curr Opin Psychiatry.
2008; 21: 206–10.
7 Donne J. Devotions upon Emergent Occasions. Raspa A, editor. Montreal, QC: McGill
Queen’s University Press; 1975.
8 Meier DE, Beresford L. Growing interface between palliative medicine and psychiatry.
J Palliat Med. 2010; 7: 803–6.
9 Finlay I. In: Lloyd-Williams M, editor. Psychosocial Issues in Palliative Care. Oxford:
Oxford University Press; 2003. p. viii.
CHAPTER 2
Adjustment and anxiety
The human race is the only one that knows it must die, and it knows this
only through its experience. A child brought up alone and transported to a
desert island would have no more idea of death than a cat or a plant.
Voltaire (1694–1778)1
Dying is a personally unique experience and one that we cannot share with
another, nor rehearse with any certainty as to how it will be. Yet we know it will
happen. ‘Never-before-encountered’ psychological challenges are presented to
the terminally ill.2 ‘Can this be death?’ thought the mortally wounded Prince
Andrew in Tolstoy’s War and Peace, moments before his death. For many, until
they are incurably ill, consideration of the psychology and spirituality of death
is not contemplated with seriousness. Adjustments and anxieties are inevitably
created.
ADJUSTMENT DISORDER (OR DISTRESS)
Care more particularly for the individual patient than the special features
of the disease.
William Osler (1849–1919)3
The Diagnostic and Statistical Manual of Mental Disorders (DSM) IV and

International Classification of Diseases (ICD-10) diagnostic criteria for adjust-
ment disorder are imprecise and nebulous.4 Though a relatively commonly used
diagnosis, the relationship of adjustment disorder to other psychiatric disorders
is unclear and there is a lack of research data to support its utility.5 Conceptually,
adjustment disorder may be a subthreshold form of post-traumatic stress disor-
der,5 or merely be a diagnostic creation to satisfy the American health insurers
5
and permit financial return to health professions. By DSM definition, within

1–3 months of a triggering event, emotional disturbance (marked distress in
excess of expected) and behavioural changes (impairment of social/occupational
functioning) occur, which are not able to be diagnosed as another mental disor-
der. Anxiety, depressed mood and conduct aberrations are often the prominent
symptoms, yet not of the intensity or persistence to meet the specific diagnostic
criteria for these conditions. Adjustment disorder refers to someone who is
distressed and ‘not coping’, having recently experienced a stressor, such as a
malignant diagnosis, a treatment complication or the awareness of impending
death. If the identified stressor is a ‘traumatic event’ (according to DSM-IV cri-
terion A) a post-traumatic diagnosis is preferred.5
Adjustment disorder is reported in 32% of cancer patients, and 35% of cancer
sufferers are clinically significantly distressed.6 These would appear to be surpris-
ingly low figures, for at stages it is probable that all cancer patients struggle with
their emotions and coping. ‘Distress’ is not defined in the medical literature.
Rather than attempting to differentiate adjustment difficulties from sadness,
sorrow, grief, subclinical anxiety, depression and Axis-1 DSM-IV diagnoses, it
may be more useful to use the term ‘distress’. Distress rather than the medical
condition of adjustment disorder would avoid psychiatric stigmatisation and
acknowledge an expected and normal reaction to an unsettling life event. Risk
factors including low ego strength, passive or avoidant coping style, inadequate
or inappropriate information, lack of social support, communication problems,
treatment-related stressors, number of unresolved concerns and level of partner’s
distress have been identified.7 Lack of coping flexibility may well predispose
persons to difficulties problem-solving and adjusting to the new problems a
malignant illness presents.8 It is difficult to conceive a greater stressor than that of
a terminal illness, irrespective of the resilience and resourcefulness of the patient.
Indeed, those few persons who respond to such illnesses without a behavioural or
emotional flinch are probably more likely to suffer significant psychopathology.
Management
There is no empirical research providing information on the most effective
treatment of adjustment disorder or its natural course.9 Adjustment disorder
is by definition a self-limiting disorder once the stressor is removed,5 however
this is unlikely in cancer patients and the distress suffered may be so severe that
treatment strategies need to be offered.5 Possessing appropriate and adequate
information, most individuals with the support of their family and social
network adjust and adapt. The innate resourcefulness of most is remarkable.
Information and empathic (not sympathetic) support provided by the attending
medical and nursing staff is surely helpful. Too much complex information, often
provided in the modern climate of non-paternalistic medicine, risks enhancing
ADJUSTMENT AND ANXIETY 7
distress and indecision of the individual. A fundamental and reassuring task of

the health professional is, ironically, to reinforce the normality of distress. Some
health professions, particularly psychiatrists, often have little to offer for they are
inclined to somewhat trivialise distress or convert it into a medical condition
that they think they know how to treat.
Self-help groups may have a role and for some, individual and/or group psy-
chotherapy may be of benefit. Psychodynamic interventions based on a trusting
relationship and the relating of earlier experience to the current one is the most
effective form of psychotherapy for adjustment disorder.10 Cognitive–behav-
ioural approaches are, however, more commonly practised these days. While
there is undoubtedly a role for specialist psychotherapists with those struggling
profoundly with adjustment distress, the therapeutic costs of making normality
into pathology need to be carefully ascertained. The ideal assistance is that pro-
vided by the patient’s natural support network. Nursing staff are the best-placed
professionals to provide support, however, specialist counsellors also have a role,
perhaps an increasing one.
Very short-term and intermittent hypnotic use may be helpful during the
crisis period. Insomnia may perpetuate a vicious cycle of distress and fatigue,
each amplifying the other. Arresting this cycle can be most beneficial. There is no
evidence that antidepressant or antipsychotic medications ameliorate distress. In
some communities and cultures alcohol is used. Alcohol is an effective remedy
for initial insomnia, until tolerance develops, but it disturbs the sleep architec-
ture and dreams, and fitful awakenings tend to negate the advantage of ease of
falling off to sleep. Habitual use and physical dependence can be initiated by an
adjustment crisis. Drugs are best avoided; adjustment distress is a psychological
process and requires, and is eased by, psychological interventions.
The passage of life is a procession of adjustments to minor and major events.
Sadness and distress invariably occur. Such experiences can initiate psychologi-
cal growth and maturation. Pathological interpretations of adjustment or distress
reactions are rarely therapeutic. Distress and cancer are naturally associated.
This doesn’t mean psychotherapy is not helpful. The illness may be a therapeutic
opportunity for both patient and family to sort not only the current, but also
older, troubles.
FRIGHT, FEAR AND ANXIETY
Objects of fear are of two kinds – the reasonable (death and surgical opera-
tions) and the unreasonable (thunder, darkness, ghosts, speaking in public,
sailing, riding, certain animals, particularly cats, rats, insects and the like).
Benjamin Rush (1746–1813)11

A sudden, unexpected sensory stimulus may result in fright, a pre-emotional,

innate, reflexive reaction characterised by a startle response. This ‘clears the
neural slate’ of competing behaviours allowing for rapid motor readiness to react
to the stressor. Hopefully, frights are unusual and avoidable in palliative care.
Fear is a universal and briefly unpleasant emotional response caused by
anticipation or awareness of danger. Some fear stimuli are innate, such as pain,
bleeding, physical proximity, confined spaces, unpleasant odours, nasty tastes
and snakes. Many fears are learned, often as a consequence of an aversive expo-
sure. These may include fears of dying, death, being buried alive, needles and
unpleasant medical treatments such as chemotherapy and radiotherapy. Fear
is a common, probably universal, complication of severe medical illness. Fear
initiates a behaviour reaction – aggressive defence (‘fight’), avoidance (‘flight’),
immobility (‘freezing’) or appeasement (‘submission’). Associated are symptoms
of physiological and psychological arousal, the latter usually rising subsequent
to the immediate survival behavioural response.
It was not until the eighteenth century, and particularly the era of Freud
in the late nineteenth century, that the concept of anxiety was introduced to
medicine, though philosophers such as Spinoza, Pascal and Kierkegaard had
previously considered the rationality of human responses to challenge or conflict.
Kierkegaard (1813–55) first differentiated fear and anxiety suggesting that in fear
one moves away from the feared object, whereas the anxious person maintains
an ambivalent yet persisting relationship with the conflictual situation.12 Anxiety
is prompted by generalised, non-specific threats and cues. It is objectless, the
threat is to the ‘self ’, to one’s existence. It is a sustained and irrational response.
The reaction, though understandable, is grossly exaggerated. Whereas in fear the
neural processes are automatic or reflexive, in anxiety cognitive processes are
involved in evaluating and responding to the threat, which may be externally or
internally derived. The dissolution of the self is the perceived peril of the anxious
person.
Fright, fear and anxiety are adaptive, indeed creative, responses to danger.
However, if severe and protracted they cause suffering, which should be man-
aged. Approximately 8% of patients with advanced cancer, particularly younger
women, suffer an anxiety disorder, most commonly generalised as anxiety or
panic disorder.13 In those with terminal illness, as a realistic appraisal of health
status becomes apparent, the prevalence is higher, approximately 14%.14 Left
untreated, anxiety is associated with increased pain, increased desire for has-
tened death, and increased disability. Modern psychiatry has been lazy in its
lack of differentiating fear and anxiety, using anxiety as the preferred term. The
prevalence of fear in palliative patients has not been determined. Few would
be expected to avoid some moments of fear during the course of their illness.
Though the physiological, emotional and cognitive symptoms of fear and anxiety
are similar, they are distinct responses to differing types of stimuli. They are
demanding of different management strategies.
ANXIETY STATES
Acute situational anxiety and panic attacks
The receiving of ‘bad news’, the discomforts and the humiliations of medical
procedures, and the dawning awareness of illness progression are but a few of
the predicaments precipitating acute anxiety in the terminally ill. It may also be
precipitated by the withdrawal of active treatment rendering the patient ‘unpro-
tected’ or ‘abandoned’.15 The psychological adaptation from curative to palliative
care is an anxious phase. The prevalence of pure anxiety symptoms in cancer
patients is not established, for often mood symptoms coexist and panic attacks
are presumed to be ‘normal’. Lewis, in the 1930s, proposed a continuum between
anxiety and depression and believed they could not be usefully distinguished,16
an opinion that to this day has not been convincingly refuted.17 In practice, ‘nerv-
ous’ patients are frequently encountered (see Box 2.1). If the anxiety response is
very severe and abrupt, it is referred to as a panic attack. Anxiety fades sponta-
neously and is extinguished, but is easily reactivated by lesser stimuli for some
period of time. Somatic symptoms activate the central discomfort, and vice versa,
thus a self-perpetuating cycle can be initiated.
BOX 2.1 Symptoms of anxiety
Psychological: apprehension, panic, inappropriate fear, foreboding, dread,

tension, intrusive thoughts of death, catastrophic thoughts, depersonalisation,
derealisation, irritability, initial insomnia, impaired concentration, slowed thinking.
Physiological/somatic:
● gastrointestinal: dry mouth, diarrhoea, indigestion (‘butterflies’), anorexia,
nausea, dysphagia (‘globus hystericus’)

● cardiovascular: palpitations, chest ache, tachycardia
● respiratory: hyperventilation (‘air hunger’), yawning, sighing
● nervous system: headaches, dizziness, tremor, paraesthesia, shakiness,
muscle twitching, restlessness

● genitourinary: urgency, impotence
● dermatological: sweating, rash.
Most people at some crisis during their life, such as before an examination or
after a frightening occurrence, will have experienced a panic attack. In situa-
tions of profound and real danger, panic is rare: rather a sense of calmness and
clarity pervades, not unlike its pain equivalent, stress analgesia. Anxiety has a
purpose, like inflammation. Anxiety is the psychic equivalent of pain. It mobi-
lises the organism to achieve some mastery over the provocative stimulus so it
doesn’t again disturb equilibrium. Anxiety, like ‘stress’, functions in constructive
and adaptive ways, and indeed psychotherapy utilises this discomfort to incite
change. Its essential function is reparative. A little is invigorating but too much
is disastrous.
Anxiety may also be pathological. The behavioural consequences, such as
fleeing treatment or refusing interventions, may be damaging. Some have a ‘trait’
propensity to high resting anxiety, thus their threshold is lower. Unprovoked
panic is suggestive of it being secondary. Anxiety and panic may be symptomatic
of primary psychiatric illnesses such as generalised anxiety, post-traumatic stress
disorder or affective disorder. Organic disease creates anxiety. Uncontrolled
pain evokes anxiety. Thyroid, parathyroid and adrenocorticotrophic hormone
(ACTH)-secreting tumours may cause anxiety. Corticosteroids, respiratory
stimulants, drug withdrawal states (included in the elderly diurnal withdrawal
symptoms from short-acting hypnotics), neuroleptic-induced akathisia and
any major current or impending physiological challenge (such as a pulmonary
embolus) may be accompanied by anxiety.17 Disease of the central nervous sys-
tem provokes a ‘free-floating’ anxiety, and in palliative care cerebral tumours
and metastases may drive such discomfort independently of any environmental
or interpersonal stressors.
Management
PSYCHOLOGICAL
Verbal reassurances and explanation may not be able to be immediately assimi-
lated because of the cognitive compromise. Touch and stroking may be more
effective anxiolytic interventions, and merely the presence of a concerned other
may be therapeutic during a crisis. Focusing attention on slow, regular breath-
ing and relaxation serve not only to distract but also to allow carbon dioxide
to build up and physiologically check hyperventilation. Breathing into a paper
bag is another option, though some can’t tolerate the bag over their mouth and
nose. Panic is not dangerous – fainting, heart attacks and insanity rarely occur.
‘Fighting it’ merely prolongs it. Once over the peak, many are ripe to benefit from
guidance or interpretation, this being a fundamental tenet of psychotherapies.
Further extensive and expensive investigations, with the expectation of normal
results, do not necessarily reassure the patient (only the doctor).18 If the anxiety
is persistent, individual behavioural and cognitive psychotherapies are indicated
and effective in the short-term.19 A goal is to teach self-management strategies,
emphasising the patients’ central role in managing their illness and its stressors.
PHARMACOLOGICAL
Medication can allow the psychological interventions to be acceptable to the
patient and able to be applied with effect. Medication and psychotherapy are
complementary.
Benzodiazepines
The most effective intervention, if the above are not proving effective, is benzo-
diazepine (BDZ) medication. Benzodiazepines lower overall anxiety and also
reduce anticipatory anxiety. For acute anxiety they have greater efficacy than
antidepressants, beta-blockers and buspirone.20 Clonazepam (0.25–0.5 mg)
as oral drops or tablet takes up to 20 minutes to be active, as does lorazepam
(0.5–1.0 mg). However, subcutaneous midazolam (2.5–5 mg) within moments
contains a crisis. The type, dose and route are determined by the urgency of the
mental state and the preference of the prescriber. BDZs are extraordinarily ver-
satile and can be administered by multiple routes – oral, intranasal, sublingual,
buccal, per rectum (PR), subcutaneous (SC), intramuscular (IM) and intravenous
(IV). If hepatic functioning is severely compromised, oxazepam and lorazepam
are renally excreted and therefore a preferable option. The anxiolytic action
of benzodiazepines may fade over time and tachyphylaxis may occur (but not
invariably), hence the recommendation of short-term use. For most it takes at
least several weeks for therapeutic fade to occur. Anxiety, even in crisis, waxes
and wanes, thus there is continuous variation of dosage requirement, thus
encouraging tachyphylaxis.
Other anxiolytics
The azapirone, buspirone, is as efficacious as BDZs in uncomplicated generalised
anxiety disorder, is well tolerated and has low potential for dependence, but it
may take weeks to show clinical effect. Buspirone may have a specific role in
organic anxiety. Barbiturates remain the ultimate backstop for intractable acute
anxiety. Beta-blockers (propranolol 20–40 mg orally) may block the somatic
symptoms and interrupt the vicious cycle.
Antidepressant medications
The misnamed antidepressant medications, particularly the selective serotonin
reuptake inhibitors (SSRIs), are the most effective long-term medication for
chronic anxiety.
Fears
It is faere [fear] I stand most in faere [fear] of.
Montaigne (1533–92)21
The fear of illness and death is universal. The illnesses most feared are those of
madness, spinal injury and cancer. Death anxiety is the fear of non-being, of
not existing. Surveys have shown 50–80% of cancer patients have concerns or
troubling thoughts about death.22 Death fear is independent of religion and reli-
gious practice.22 Religiosity may camouflage these fears. Spirituality and religious
faith may be coping strategies, and perhaps protective ones. Death anxieties may
centre on particular concerns such as fears of the manner in which one may die,
of life being meaninglessly medically prolonged, of pain and disfigurement, of
loss of personal desirability, of being dependent and a burden, of financial and
employment losses, of the future care and safety of dependents, and of aban-
donment by relatives, friends and professional carers. The core theme to these
concerns and fears is the loss of control, independence and autonomy associated
with the unwanted ‘sick and dying role’.
George Washington gave instructions in his will that his body should be kept
above ground for three days before burial. Such was Hans Christian Andersen’s
fear of being buried alive that every night he would place a note on his bed to
say that he only appeared to be dead. The fear of being buried alive (taphopho-
bia), a primal fear, is perpetuated by sensational reports of the ‘dead’ awakening,
though is less commonly a fear in the modern world than in centuries past.23 It
stimulated the invention of elaborate warning systems able to be operated from
within a coffin, encouraged medical debate on the signs of death and influenced
the usual (slow) pace of funeral arrangements. However, in cultures and societies
in which belief and/or environmental conditions prefer quick burial (by sunset),
such fears may be more prevalent. The ponderous ritual of auscultating the chest
to certify death is a historic remnant of medicine trying to reassure the living
that only when dead will they be buried.
Management
If the reaction is to an innate fear stimulus then the therapeutic response is to
limit reinforcing the avoidance behaviours and to sooth the physiological and
psychological reactions. However, if the fear reaction is acquired through prior
exposure to an aversive experience, cognitive and behavioural interventions can
be therapeutic. William Heberden (1710–1801) suggested ‘physicians . . . should
disarm death of some of its terrors’.24 Providing a safe opportunity to express
these concerns and fears, education and reassurance are the core components
of management. Gentle exploration of the beliefs and personal experiences that
may have reinforced such fears may be necessary, and for some, more intensive
psychotherapy may be required. Because of the novelty of the experience of dying
for the individual, the professional alliance with the attending staff, experienced
in caring for the dying, may be invaluable. Non-abandonment and the intense
desire to contain distress and suffering are crucial staff attitudes. However, the
primal and fundamental nature of fears about death remains for many, at least
to a minor degree.
Phobias
A phobia is an irrational fear of a specific situation. It results in an excessive and
unrealistic avoidant reaction to a fearful stimulus. It can’t be explained away,
though the sufferer recognises it to be an extreme, if not silly, response. Exposure
results in panic thus most prefer not to risk this. The commonest simple phobia
in oncological practice is needle phobia, a condition that affects up to 10% of the
population. The needle puncture triggers an inherited vasovagal reflex of shock
and successive needle exposure results in an additional learned reflex.
Phobias may be of doctors, hospices, radiation therapy and chemotherapy.
Anticipatory nausea and vomiting (ANV) is a conditioned response to envi-
ronmental cues related to the chemotherapy experience.15 As chemotherapy
courses extend, the intensity of ANV tends to enhance, further reinforcing the
phobia. Marcel Proust wonderfully described the sensory cues initiating remem-
brance (and phobias).25 The smell of a hospital may evoke fearful memories.
Claustrophobia created by the confinement and noise of magnetic resonance
imaging (MRI) scanning is not uncommon.
Agoraphobia and social phobia occurring early in the course of illness may
delay the seeking of medical care or compromise the attendance at treatment.
These pathological conditions lie at the extreme of a continuum from shyness
to social avoidance, and are of relevance to ‘illness behaviours’ for they can
adversely influence attendance at the doctor.
Management
Phobias respond well to graded exposure or desensitisation behaviour therapy.
Support and explanation are essential components and occasionally background
SSRI or BDZ (or for needle phobia topical anaesthesia) cover is necessary. The
weight and demands of disease and treatment may flood the patient, paradoxi-
cally resulting in a ‘self-cure’.
BENZODIAZEPINES
Much maligned since the early 1970s, benzodiazepines (BDZs) have safely
transformed the acute medical management of anxiety. Superior in potency and
tolerability to their predecessors such as bromides and barbiturates, their benefits
have been underestimated and their risks of dependency overestimated.20 At low
dosage BDZs are anxiolytic, at high dosage they are sedative. Clinically they are
easily titrated, however, in the mid-range dose (or combined with alcohol) they
may cause a state of acute intoxication. It is mainly for these reasons that they
have acquired a contentious reputation. The individual BDZs differ in half-life
(related mainly to metabolism, not absorption) and potency, though all interact
with BDZ receptors and increase gamma-amino butyric acid (GABA) inhibi-
tion. Judicious prescribing in the medically ill dictates that the short-acting
BDZs should be used. The preference for clonazepam by many in palliative care
may be based on history and availability rather than pharmacology. However,
with very short acting BDZs, such as midazolam, rebound anxiety may occur
between doses.
BDZs are a crucial medicine in the armamentarium of palliative care. They
are used as anxiolytic agents, hypnotics, anticonvulsants and sedatives, for acute
dyspnoea, delirium tremens, spasm and drug withdrawal states. Though expen-
sive and with a short storage life, there is an antidote available – flumazenil. This
has also been trialled therapeutically in hepatic encephalopathy.26 The concerns
regarding potential adverse events of BDZs have probably been overestimated
in risk–benefit analyses, certainly at least for the palliative care patient.
Respiratory depression
Parenteral BDZ may induce transient respiratory depression in BDZ-naive per-
sons, as many junior doctors treating prolonged seizures have discovered to their
horror. This has not been reported for oral or rectal BDZs alone. Sleep apnoea
and snoring may be enhanced, and a decrease of the ventilatory response to
hypercapnia has been demonstrated.27 In animal studies, IV administration, and
not oral, was required to induce respiratory depression.28 While the availability
of the antidote flumazenil is reassuring, BDZs should be used with caution in
the respiratory-compromised patient. Yet in the management of severe dyspnoea
this adverse reaction is not problematic unless the dose is deeply sedating.
Dependence and addiction

Physiological dependence, as expressed by withdrawal symptoms (insomnia,
tremor, sweating, tachycardia, light sensitivity, optical distortions, deperson-
alisation, derealisation, nervousness, seizures, delirium), depends primarily on
the duration of treatment and the dose of BDZ. Withdrawal symptomatology,
which occurs in up to 80% of patients, normally appears only after treatment of
more than 4 months’ duration,20 and 2–3 days after abrupt cessation of short-
acting BDZ and 5–7 days after long-acting BDZ discontinuation.29 Symptoms
tend to be more intense with short-acting BDZ withdrawal and clinically need
to be distinguished from rebound phenomena; that is, the dramatic return of
the original anxiety symptoms. There is a distinct emerging trend to maintain
that small group of chronic anxiety sufferers who are not responsive to other
interventions and who are on BDZs long term, as these disorders tend to be
relapsing. Dose escalation tends not to be a problem, nor does fading efficacy,
though physiological dependency needs to be acknowledged for these patients.
Apart from dependency, there is no evidence of psychiatric morbidity caused by

long-term use of BDZ.30 The risk of addiction and abuse of BDZs increases with
duration, dosage, short-action BDZ, severity of symptoms, additional stressors
and for certain personality types (dysthymic, anxious, borderline).20,30,31 Rapid
dose escalation, drug seeking and reports of mislaid prescriptions may indicate
the emergence of psychological dependence, but this adverse event is unusual
in the acutely medically ill. The chaotic drug-dependent patient with recently
diagnosed cancer may ‘arrive’ at palliative care addicted to many substances
including BDZs. The more important clinical concern in palliative care is the
thoughtless cessation of long-term BDZ prescribed for anxiety or insomnia
and the resultant withdrawal symptoms. Gradual tapering of the dose with a
view to eventual withdrawal may not be a practical option in palliative care.
Administering a longer-acting, maintenance BDZ is usually more feasible and
humane in the dying.
Paradoxical behaviours
Disinhibition or aggressive dyscontrol in patients treated with BDZs is uncom-
mon. Dietch estimated the incidence of behaviours such as irritability, verbal
hostility and frank assault associated with BDZs to be less than 1%.32 At-risk
persons include the neurologically impaired, the elderly, adolescents, alcohol and
substance users, the severe personality disordered and those with pre-existing
impulsive behavioural problems.33 However, in a retrospective chart review of
323 psychiatric inpatients (a high-risk group) prescribed either alprazolam or
clonazepam, and a control group who received no BDZ, no differences between
the groups as to behavioural disinhibition could be found.31 BDZs may unmask
underlying depressive affect; however, in the anxious dysthymic they may relieve
such symptoms. BDZs are similar to alcohol in that the effects vary with the
dose. In the frail terminally ill it is prudent to dose with care and avoid intoxi-
cating mid-range doses, which may contribute to confusion and increase the
risk of falls.
Amnesia/cognitive impairments
Amnestic disorders have been reported, with high dosage of short-acting
BDZs, specifically triazolam and lorazepam. These dose-dependent memory
losses principally affect the assimilation of new information into the long-term
memory and not memory contents previously learned. Usually the deficit is
short lasting and reversible, and with chronic BDZ administration tolerance
to memory deficits appears to develop.34 Lipid solubility may be a factor, clon-
azepam being the least likely to cause memory impairment.34 The beneficial use
of short-acting high-potency BDZ to abolish traumatic memories of a horrific
procedure or medical event, such as awareness during anaesthesia, has been
advocated. Combination with alcohol amplifies the risks of neuropsychiatric

adverse reactions of BDZs significantly. Tiredness and drowsiness affecting
concentration and impairing motor function can occur early in treatment, with
high dosage, and particularly in the frail elderly. Interestingly, these problems
are more detectable in normal subjects than anxious patients. While the sedation
may be beneficial at night, it is a dangerous side effect by day, greatly enhancing
the risk of falls and dulling the quality of remaining life. Clinically, these risks
need to be weighed against the inconvenience and the non-pharmacological
hangover of a sleepless night. Untreated insomniacs are more at risk for daytime
drowsiness and despondency than those using BDZ hypnotics.35 Tolerance to
the sedating adverse reactions tends to occur; it is less certain if tolerance to the
anti-anxiety and hypnotic effects evolves. Metabolic tolerance to BDZs does not
occur; at high dose, minor functional tolerance may occur.
POST-TRAUMATIC ANXIETY STATES

Traumatic experiences are sadly a part of life for many, if not most. An American
citizen’s lifetime exposure to traumatic events shows that the exposure rate
to life-threatening illness is 4.7/100, a little less than the risk of being shot or
raped, and considerably less than being involved in a motor vehicle accident at
28/100.36 The normal response to a sudden, unexpected and distressing event
is a transient acute stress disorder (ASD). ASD ensures immediate emotional
anaesthesia following the trauma and an exaggerated arousal state in order to
help survive the crisis. Like grief, over time (and in a safe environment) these
symptoms spontaneously resolve, and within 12 months for the majority the
troubling symptoms have dissipated. Yet intrusive recollections and nightmares
of the event and symptoms of physiological readiness for ‘flight or fight’ can still
be cued by reminders, particularly sensory ones. Some with ASD may develop
post-traumatic stress disorder (PTSD) (see Box 2.2). PTSD is a disorder induced
by fright undermining an individual’s sense of safety and exposing their vul-
nerability and powerlessness. It is a complex biopsychosocial disorder and not
merely a psychological reaction to a terrible occurrence. The symptoms of PTSD
have adaptive survival purposes until such time as the threat to life has abated,
at which stage these persisting symptoms are maladaptive. A cost of modern
oncology practice ‘converting’ cancer to a chronic life-threatening disease is that
psychological traumatic opportunities are also increased. While up to 93% of
the general population report exposure to traumatic events, only approximately
5–12% develop PTSD.37 The vast majority of those exposed cope with great for-
titude and without ongoing psychological or psychiatric symptoms. The lifetime
prevalence of PTSD in the general population is 5–6% of men and 10–12% of
women.38 The prevalence of chronic PTSD in veterans of war is approximately
15%, though many, particularly veterans of WWII, may not have an established
diagnosis. The probability of evolving PTSD is dependent on the type of trauma

(exposure rate/100: life-threatening illness 1.1, rape 49.0), sex, past psychiatric
history, prior traumatic history (trauma is cumulative), low education, social
status, age and many other factors. The commonest psychiatric sequela of trau-
matic exposure is depressive disorder.
BOX 2.2 Post-traumatic stress disorder
Exposure to a traumatic event: involving the perception of life being threatened.

Symptoms:
● re-experiencing cluster: recurrent and intrusive recollections of the
traumatic event, recurring distressing dreams and nightmares, dissociative

reactions (e.g. flashbacks)
● avoidance/numbing cluster : avoiding thoughts, feelings and stimuli of the
event, amnesia for part of the event, detachment, reduced ability to feel
emotions
● hyperarousal cluster: anxiety, hyperalertness, insomnia, exaggerated
startle reflex, irritability, angry outbursts, poor concentration, safety

consciousness.
Duration: acute <3 months, chronic >3 months.
Cancer, particularly at the time of diagnosis, can induce posttraumatic

symptoms.39 Medical diagnoses and procedures may result in extreme fear, help-
lessness, or horror; these reactions being required descriptors of the DSM-IV
criteria for a traumatic stressor. The degree of fear of dying is related to the risk.40
Alter reported that nearly half of a group of cancer survivors reported post-
traumatic symptoms, with 4% meeting a current diagnosis of PTSD.41 Current or
past PTSD diagnosis in HIV-positive men was found to be 30%.42 The likelihood
of PTSD is, however, lower among medical patients compared to, for example,
rape victims. Much of the trauma literature concerns young women with early
breast cancer where such a diagnosis is clearly catastrophic. As is to be expected,
such symptoms are prone to reactivations at various stages through the illness,
for reminders cannot be avoided if a hospitalisation or a procedure is necessary.
But not only are the rates of post-traumatic symptoms low following medical
illness, the symptoms that evolve tend not to be typical of classical PTSD. The
precipitating stressor, the illness, is not ‘man-made’ or involving interpersonal
violence, though medical complications may be perceived to be. Naturally occur-
ring stressors and disasters are less intense stressors and generally illness, even
if contributed to by risky behaviours such as smoking, excessive use of alcohol
and extreme sun exposure, is interpreted by most as ‘fate’ or misfortune. An

ongoing treatment-related stressor can be prepared for and should take place
in a supportive environment, a feature that further mutes helplessness and hor-
ror. The intrusive thoughts, dreams and nightmares of these patients are often
future-orientated.39 They may concern fears of relapse, mutilation, pain and
dying. They are not the repetitious, recurrent recollections of the traumatic event
of classical PTSD. In fact they are more typical of pervasive worry and anxious
apprehension of generalised anxiety disorder.39 Neither are the sympathetic
nervous system-driven arousal symptoms and signs associated with the intrusive
thoughts so evident. Medical events are more prone to induce chronic anxiety
than post-traumatic states such as ASD and PTSD.
Victims of severe trauma such as Holocaust survivors, Indochinese boat peo-
ple, displaced refugees and war veterans require particular consideration. The
diagnosis of a fatal illness and associated re-exposure to dying may reactivate
earlier close-to-death experiences.43 The pain and cachexia of advanced cancer
serve as vivid reminders of torture or starvation, and the loss of control over
destiny undermines active coping strategies and the conscious memory sup-
pression that had allowed at least a semblance of quality of post-traumatic life.
Families report that PTSD-related symptoms are quite common near the end of
life in veterans’ populations and that they cause significant levels of discomfort. 44
Management
Ensuring safety, rest and sleep, medical stabilisation, allowing patients to ‘tell
their story’ (but only if they have a need to) and providing an emotionally warm
and supportive environment is necessary ‘emotional first aid’. The critical ingre-
dient is the retention of the victim’s remaining personal competency and coping
strategies, to allow rapid regaining of some control and dignity.45
In acute traumatic situations, critical incident debriefing and reworking
(cathartic/exposure) therapies have been shown to increase the risks of PTSD,46
though they may be therapeutic for ASD. Indulgent and vicarious interest in the
trauma story may be as damaging as blatant disinterest. Minimising the distress
and secondary sequelae (secondary prevention) is important in preventing
persistence of symptoms. Containment and not catharsis is required. Psycho-
education, psychological interventions (e.g. relaxation techniques, cognitive
behavioural therapy), pharmacological anxiolysis (short-term benzodiazepines,
opioids, SSRIs, alpha2-adrenergic blockers, beta-blockers) and the pursuing of
ongoing interest and attention in the person and their experience are all of thera-
peutic value for those traumatised by their illness and/or its treatments. Initial
use of a hypnotic agent, followed up after 3 weeks (if necessary) by an SSRI has
been recommended for acute persistent PTSD symptoms in primary care.47
ASD has an excellent spontaneous recovery rate, as has acute PTSD, for
60% have been shown to remit spontaneously within 6–12 months.48 But once
chronic, PTSD is notoriously difficult to effectively treat. As yet, preventing
PTSD is not possible. Palliating its symptoms is often achievable by combinations
of psychotherapy and pharmacotherapy. Assertive management of comorbid
conditions such as major depressive illness and substance misuse (perhaps initi-
ated as self-treatment) is important. Establishing a therapeutic alliance with the
traumatised is difficult. Even the grave symptoms of terminal illness and atten-
tive care may not persuade the patient to trust in another. The multidisciplinary
care provided, the distractions of physiological symptoms of malignant disease,
and psychotropic medications can in combination sometimes overcome these
barriers and allow a belated therapeutic opportunity for the sufferer of trauma.
POST-TRAUMATIC GROWTH
As the strength of the body lies chiefly in being able to endure hardships, so
also does that of the mind.
John Locke (1632–1704)49
Psychological development, maturation and ‘growth’ can be precipitated by

difficult and traumatic events, such as severe medical illness. This phenom-
enon has long been recognised in philosophy, literature and religion.49,50 Some
patients consider themselves ‘better persons’ consequent upon this experience.
Improved interpersonal relationships, an enhanced sense of spirituality and a
greater purpose in life, in patient and partner, are examples of such changes.51
Estimates of the prevalence of these consequences range from 40% to 70%.52,53
Stable pre-cancer personality and social functioning are predictive factors.
There is a consistently linear relationship between the degree of trauma and
growth.51 Greater stress related to the illness and greater perceived risks to life
are associated with adversarial growth.53 The precipitating event is required to
be ‘seismic’, sufficient to shake basic assumptions about the self and the world.54
Post-traumatic growth (PTG) can be accompanied by post-traumatic stress
symptoms, however the aetiological stressors in PTG and PTSD differ. Fear may
induce cognitive and behavioural change, fright can result in negative sequelae
including PTSD.55 If illness psychologically shakes rather than startles an indi-
vidual’s world, it can be a positive psychological event.
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17 Himmelhoch J, Levine J, Gershon S. Historical overview of the relationship between
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18 Howard L, Wessely S, Leese M, et al. Are investigations anxiolytic or anxiogenic? A
randomised controlled trial of neuroimaging to provide reassurance in chronic daily
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19 Osborne RL, Demoncade AC, Feuerstein M. Psychosocial interventions for depression,
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2006; 36: 13–34.
20 Moller H-J. Effectiveness and safety of benzodiazepines. J Clin Psychopharmacol. 1999;
19(Suppl. 2): 2S–11S.
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Book 1. New York: AMS Press; 1967. p. 67.
22 Cherny N. The treatment of suffering in patients with advanced cancer. In: Cochinov
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Oxford University Press; 2000. p. 385.
23 Bondeson J. Buried Alive: the terrifying history of our most primal fear. New York: WW
Norton; 2001.
24 Heberden W. Commentaries on the History and Cure of Diseases. Ch. 51. Quoted in:
MB Strauss, editor. Familiar Medical Quotations. Boston: Little, Brown & Company;
1968. p. 159.
25 Proust M. Remembrance of Things Past. Scott Moncrieff CK, trans. London: Chatto &
Windus; 1952.
26 Bostwick JM, Masterson BJ. Psychopharmacological treatment of delirium to restore
mental capacity. Psychosomatics. 1998; 39: 112–17.
27 Cohn MA. Hypnotics and the control of breathing; a review. Br J Clin Pharmacol. 1983;
16: 245S–50S.
28 Sakai Y. Comparative study on the depressive action of several benzodiazepine minor
tranquilizers [Article in Japanese]. Nippon Yakurigaku Zasshi. 1979; 75: 777–87.
29 Noyes RJ, Garvey MJ, Cook BL, Perry PJ. Benzodiazepine withdrawal: a review of the
evidence. J Clin Psychiatry. 1988; 49: 382–9.
30 Mattilla-Evenden M, Bergman U, Franck J. A study of benzodiazepine users claiming
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31 Rothschild A, Shindul-Rothschild JA, Viguera A, et al. Comparison of the frequency
of behavioral disinhibition on alprazolam, clonazepam or no benzodiazepine in hos-
pitalised psychiatric patients. J Clin Psychopharmacol. 2000; 20: 7–11.
32 Dietch JT, Jennings RK. Aggressive dyscontrol in patients treated with benzodiazepines.
J Clin Psychiatry. 1988; 49: 184–8.
33 Paton C. Benzodiazepines and disinhibition: a review. Psychiatr Bull. 2002; 26:
460–2.
34 Chouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal and
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35 Balter MB, Uhlenhuth EH. The beneficial and adverse effects of hypnotics. J Clin
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37 Lee D, Young K. Post-traumatic stress disorder: diagnostic issues and epidemiology in
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38 Resnick PA. Stress and Trauma. London: Psychology Press; 2001.
39 Mundy E, Baum A. Medical disorders as a cause of psychological trauma and post-
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48 Kessler RC, Sonnega A, Hughes M, Nelson CB. Posttraumatic stress disorder in the
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49 Locke J. Some Thoughts Concerning Education and of the Conduct of the Understanding.
RW Grant, N Tarcov, editors. Indianapolis, IN: Hackett; 1996. p. 25.
50 Tedeschi RG, Calhoun LG. Trauma and Transformation: growing in the aftermath of
suffering. Thousand Oaks, CA: Sage; 1995.
51 Linley PA, Joseph S. Positive change following trauma and adversity: a review.
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53 Widows MR, Jacobsen PB, Booth-Jones M, et al. Predictors of posttraumatic growth
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54 Calhoun LC, Tedeschi RG. Posttraumatic growth: future directions. In: Tedeschi RG,
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55 Vaiva G, Brunet A, Lebigot F, et al. Fright (Effroi) and other peritraumatic responses
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ment. Can J Psychiatry. 2003; 48: 395–401.
CHAPTER 3
Psychological issues and dying
Bodies devoid of mind are as statues in the market place.
Euripides (484–406 BC)1
Much has been written of psychology as it relates to cancer. Putative psychologi-

cal causative factors, psychology affecting progress and psychotherapy all have
a considerable body of literature. There is less written about psychology in the
terminal phase of life.
PSYCHOLOGICAL RESPONSES TO ILLNESS

An adverse life event, such as an illness, induces emotional responses (e.g. anger,
fear, sadness, shame) and behavioural responses (e.g. support seeking, non-
compliance, cooperation). These are multidetermined. The characteristics of the
disease, life experience, temperament, personality, illness concept, coping styles,
and defence mechanisms impact upon the eventual responses.
Personality traits (or disorders, if severe) shape the responses. Every person
has a unique character. There are clusters of behavioural styles which encompass
most characters (see Table 3.1).2 Stressors, both psychosocial and physiological,
unmask and highlight personality traits, which are often well camouflaged by
social customs and manners. Ego defence mechanisms are automatic psycho-
logical processes by which the mind confronts the threat (see Table 3.2).3 They
serve to unconsciously rearrange the mental conflict created, and allow ‘peace
of mind’. They create a protective illusion which can be adaptive and/or patho-
logical.2 ‘Immature’ defence styles may be predictive of lower survival rates in
cancer patients.3 Ego defences are mechanisms that retain equilibrium, though
potentially at the cost of psychological symptoms. The defence mechanisms
used are closely linked to personality and maturity. Cognitive (thoughtful) and
behavioural strategies, which are referred to as coping, are also individualistic.
Preferred coping styles are personality and experientially learned methods of
23
24
TABLE 3.1 Personality and illness (adapted from reference 2)
Personality Personality characteristics Meaning of illness Countertransference Management

trait response
Dependent Needy, self-doubting, Fears abandonment Flattered initially, Reassure within limits; mobilise others
helpless, demanding seeking overwhelmed, avoidant of to share dependency; schedule regular,
reassurances patient brief consultations
Obsessive/ Orderly, meticulous, in control, Loss of control Admiration, identification, Encourage collaboration in care; provide
compulsive indecisive, restrictive emotions irritation as time- medical information; structure and
consuming routine
Histrionic Melodramatic, flirtatious, Loss of attractiveness Appeal, pity Firm, clear boundaries; clarify, not
seeking attention confront
Borderline Impulsive, unstable Loss of self Pity, attraction, saviour Firm boundaries; shared care;
relationships, identity consistency; patience
disturbances, affective
THE PSYCHIATRY OF PALLIATIVE MEDICINE
instability, self-mutilation
Narcissistic Arrogant, entitled, grandiose, Shame at loss of self- Anger, inferiority, prestige Foster and sooth battered self-esteem;
vain, indifferent to others, concept of perfection of caring for important don’t challenge entitlement; empathise
devaluing and invulnerability patient with affective emptiness
Paranoid Suspicious, litigious, Proof that the world Anger, medicolegal wary Courtesy, honesty, respect;
distrustful, moralistic, blames is against them and and defensive practice, counterprojective dialogue
others medicine is exploiting conservative decision- (acknowledge resulting feelings, not the
them making content of ideations); litigious awareness
Antisocial History of antisocial Loss of status, Fear, anger Firm management guidelines; operate in
behaviours, plausible, aloneness a safe environment
exploitative, angry
Schizoid Aloof, distant, eccentric, Fear of intrusion, Difficult to engage, Respect privacy; maintain consistent
isolated, socially awkward interference abandon quiet interest
PSYCHOLOGICAL ISSUES AND DYING 25
TABLE 3.2 Ego defence mechanism (adapted from reference 3)
Defence type Characteristics Consequences

Mature defences Suppression Healthy, admirable defences
Altruism
Humour
Sublimation
Anticipation
‘Neurotic’ defences Repression Self-harmful defences (cause personal
Displacement suffering)
Reaction formation
Intellectualisation
Rationalisation
Immature defences Denial Harmful to others (and indirectly to
Splitting self), typically used in borderline,
narcissistic personality disorders
Idealisation
Devaluation
Projection
Projective identification
Acting out
Passive aggression
problem-solving and regulating emotional response. Appraisal of the threat and

the choice of coping styles are influenced by how the patient considers the illness.
Each individual is different in the ways they respond. Responses are dynamic,
fluctuating and changing continually.
The emotive responses induced in others by the patient are termed coun-
tertransference (even if the reaction is conscious and self-acknowledged).
Professionalism should mute responses on the part of the doctor, and by recog-
nising the process and abiding by simple management guidelines, the patient’s
illness can be properly attended to (see Table 3.1).
DENIAL
Denial, an emotion-focused coping mechanism, occurs when an external reality
is too unpleasant to face.5 Denial is unconscious and aimed at an external threat
or an intolerable internal threat. Severe denial occurs in 10% of hospitalised
patients with advanced cancer, with more moderate levels of denial occurring
in 18%.6 Denial is not avoidance, which is a voluntary effort to shun the cir-
cumstances that bring stressful information to the fore, nor is it suppression.7
Suppression is a conscious or semiconscious process in which the defence is
directed towards an intrapsychic event.7 Denial can be a normal or pathological
response. It may reduce anxiety and promote optimal functioning, while also
providing time to more properly assimilate acutely presented catastrophic
information. Alternatively, it may deprive a patient of treatment opportunities
(and lead to early death).8 It has temporal variability and is not an ‘all or none’
phenomenon.5 Weisman considered that there are three orders of denial used
as defences: denying the primary facts of the illness (the symptoms); denying
the inferences to be drawn from the symptoms; and denying the possibility of
existence, of death being the end of existence.9 The illusion of health is even-
tually dismantled by the symptom burden, particularly pain. Relinquishing
second-order denial (‘this illness will not overcome me’) is the crisis of the
poor-prognosis oncology patient. The denial tends to be reinforced by the cul-
ture of modern medicine as curers, and the hopes of family. These affirmations
are usually more entrenched than those of the individual. The transition from
oncology to palliative care involves the difficult process of accepting no prospect
of cure. Letting go of all denial and confronting the meaning of one’s existence
is not tackled by many.10
Providing that adequate and comprehensible information has been given,
denial has a psychological function. Few are psychologically strong enough to
never be in denial through the course of illness. The clinician needs to determine
this function and decide if the denial is currently beneficial or harmful. Attentive
listening and observing behaviours and attitudes (which may be more revealing
than words) allow a clinical judgement to be made. Cognitive strategies that
will allow the patient to relax denial involve the titration of reality at quantities
able to be coped with. Assertive confrontation merely reinforces for the patient
the need to be sheltered from this awful information, and the denial strength-
ens. A pragmatic, problem-solving approach, allowing the patient to retain a
perception of control, and not insisting that they abandon this psychological
survival strategy, is the most likely to allow movement. Negotiating a partial, but
predominantly beneficial, solution, for a specific time, may unlock the denial.
Subsequent similar endeavours may keep the door open. Relinquishing denial
is a positive, personal act, not something that can be imposed.10 Psychological
changes and growth can proceed. Transcendence and spirituality are kindled,
particularly if the patient approaches the quandaries of the meaning of life by
surrendering all denial.10
Denial can be a marker of depression and central nervous system (CNS)
impairment.6 Denial requires competent cognitions. The lack of self-perception
of deficits, and the tendency to strive for an undisturbed state by shrinking
the environmental milieu (the death feint) caused by destructive nervous sys-
tem lesions are automatic survival strategies.11 Communication is abandoned.
Management needs to accept organic denial as being impenetrable.
HOPE AND HOPELESSNESS
I really believe there is scarcely a greater worry which individuals have to

endure than the incurable hope of their friends . . . attempting to ‘cheer’ the
sick by making light of their danger and by exaggerating their probabilities
of recovery . . . The fact is, that the patient is not ‘cheered’ at all by these
well-meaning, most tiresome friends. On the contrary, he is depressed and
wearied.
Florence Nightingale (1820–1910)12
There is no universal meaning of hope. Hope is considered the confident yet

uncertain expectation of achieving a future good which is a realistic possibil-
ity.13 Hope is essential to life. The idea of hope is generally perceived in positive
terms.14 It is multidetermined. Hope is contingent on the ability to find continued
meaning in day-to-day existence. Hope is a dynamic, which can be influenced
by others, events and the interpretation of these. Hopes do change over a life-
time and through an illness. Hope wards off anxiety and fear, and it can be a
protective shield.14 The fragility of hope was highlighted by the philosopher,
Spinoza, who defined hope in juxtaposition to fear, considering them both to be
characteristic of the person in doubt. Fostering denial may allow hope. False or
unrealistic hopes are secured by denial and may be presented as hope by health-
care professionals, patients and families.10 Hope can be propped up by unrealistic
information and promises, though such foundations are shaky. False hope can
be as devastating as no hope. Denying reality and persuading a positive attitude
risks burdening an already vulnerable patient with false optimism. Realistic hope
can provoke solace in those who are seriously ill.14 Reality is a prerequisite for
hope.10 Only by confronting the ambiguities and unfairness of human existence
can hope emerge. Hope entices different, alternate and creative cognitive and
emotional processes, thereby allowing ongoing existence, different because of
the change in health status, but still rewarding. Realistic or authentic hope is
thought to have the potential to change human existence for the better without
reaching for the unattainable.15
The relationship of hope to emotional status is intimate.16 Depression sours
the ability to hope, pain distracts from the prospect, and delirium destroys any
possibility. Those with mature defence mechanisms may cope better if hope is
low (and realistic). Those with personality vulnerabilities are further damaged
by a lack of hope.17 Hope can be undermined with both harmful and therapeutic
consequences. Fromm identified three behavioural responses to the shattering
of hope: persons resign themselves to their fate, they isolate themselves from
others and there can be destructiveness.18 Many suggest that hope should never
be destroyed, hence an excuse for not telling patients the truth. Surrendering
hope can be beneficial. The existential view is that by recognising the finality of
life, the appreciation of the present becomes enhanced. The trivialities of life can
be ignored. The poet Theodore Roethke wrote, ‘in a dark time, the eye begins
to see’.19 Surgical patients who had received colostomies and were informed
that these were permanent, had better overall life satisfaction and quality of life
at 6 months postoperatively than did those who had reversible procedures.20
Paradoxically those better off objectively may be worse off subjectively, an
accepted observation in those suffering partial, rather than complete, paraple-
gia. Knowledge that a bad situation is permanent, with no hope of recovery, can
actually enhance adaptation to the disability.
Encouraging realistic hope so the patient can then live whatever life is left to
the full may require professional assistance. The refocusing of hope from what
is no longer possible to what is more immediately important to the patient and
family is considered a fundamental therapeutic task of palliative care. Fostering
and strengthening hope is an important nursing task.14 For hope to be generated
in someone, they need to feel loved, cared for and important. It is generated from
within and sustained by others. Others, such as nurses, by ‘being’ with rather
than ‘doing’ for the patient, may convey an attitude that sustains constructive
hope.21 The psychological massaging of hope is a core task of palliative care, but
this does not necessarily mean strengthening the hope. Reframing hope may
eventually result in surrendering hope. Mature ego defences, good psychologi-
cal health and ‘mature hope’ tend to be cited as prerequisites for being able to
contemplate the ‘depth work’ necessary to address that death may be the absolute
end of existence. An intent of palliative care is to position the patient so they
have the option of letting go and exploring the ultimate mystery. Religion may
provide a framework of support for this spiritual adventure.
Withholding medical information is not favoured by patients who value
autonomy and a role in medical decision-making. Honest communication is
the norm in the West. Fears of depriving the patient all semblance of hope by
‘truth-dumping’ is how this practice is still viewed in many cultures. Family
(and the colluding medical establishment) assumes the role of carrying the bad
news. Providing information with empathy and consideration usually is para-
doxically reassuring to the patient. Ill persons are aware of their symptom load,
and ignorance tends to enhance rather than mute fears. In unfamiliar territory,
most minds, for reasons of self-preservation, consider the worst predicament,
not the safest.
Hopefulness has positive connotations of expectation, possibility and
goodness. Hopelessness is not only the deprivation or absence of hope, it is
profoundly negative. Dismal, despairing and moribund, the hopeless struggle
to survive. Demoralisation is a psychological conceptualisation of hopelessness
(see Chapter 8). It may be the loss of primordial or fundamental hope. The hope-
less do not have the capacity to hope, but being without hope does not necessarily
equate with being hopeless.
REGRESSION AND IDEALISATION
How sickness enlarges the dimensions of a man’s self to himself! He is his

own exclusive object.
Charles Lamb (1775–1834)22
The ‘dying role’, in contrast to the ‘sick role’, forces prolonged and profound
dependency and reliance on others.23 Independence is lost and control and
autonomy challenged. Lying helplessly in bed amplifies this sense of redundancy.
There is need to literally ‘hang from’ others as physical frailties rob the ability
to competently self-care. Dependency differs from attachment. The former
increases as death approaches, the later dissolves. Attachments are initially
activated by serious illness, though progressively are shed.24 It is appropriate to
be dependent at times in life, and dying is such an occasion. In response to the
threat of annihilation, regression to previous levels of functioning occurs. The
intent is to reorganise and then re-establish the self; ‘regression at the service of
progression’.25 It is not possible for the incurably ill to rejuvenate. The ensuing
state of more primitive functioning persists.
Regression refers to experiencing the emergence of past, often infantile, trends
where such trends are thought to represent the reappearance of modes of func-
tioning that had been abandoned or modified.26 It can be transient or permanent,
slight or severe, and normal or pathological. Ageing per se does not result in
psychological regression, it is dependency that compels this.27 ‘Degenitalisation’
of emotional relationships and a more pronounced interest in the oral and anal
occurs.24 The dying patient progressively sheds attachments with others, to focus
exclusively on an ‘allusory mother’. This psychological object becomes the care-
giver. The retrenchment to ‘primary narcissism’ has consequences. Increased
sensitivity and reactivity to emotional events is balanced by the psychological
soothing provided by carers.
Along the path to this state of regressive infantile existence, memories of
childhood re-ignite. For most these are pleasurable somatic memories. Laid
before the development of language these memories are sensory, predominantly
olfactory and tactile. ‘A dying man, they say, is supposed to see his whole life
unfold before him . . . in comas I imagined I was home again. I would run up
and down the red gypsum hills of my childhood, feeling the dry Oklahoma wind
brushing against my cheeks . . . the warmth of the extra blanket laid across me in
the night, my mother’s face’.28 With regression also emerges the fear of abandon-
ment. Narcissism is a fragile state. In Kleinian terms, the ‘good’ is exaggerated
to overcompensate for the ‘bad’, which is the fear of rejection.29 The infant splits
off the bad aspects, and they are warded off by denial.29 Any fear is projected
or shifted onto the idealised mothering object. Deeper regression relieves this
concern. The very primitive self has few if any relationships and no concept of
death. Thus it can experience no losses, or fears. Its experience of pain is reflex-
ive and devoid of the affective and cognitive components of pain. Gratification
is oral and satiation of needs simpler. The psychoanalytic theory as represented
by Deutsch is:
when organic activity is coming to an end . . . the sources of the impulses

and instincts must also begin to run dry . . . life-instincts and death-
instincts alike grow weaker, and, since they grow weaker simultaneously,
the conflict between them subsides of itself. The fear of death becomes
superfluous, no danger is signalled, there is no need for anxiety as a pro-
tective warning.30
Fusion with ‘mother’ is comforting.
Tranquillity in the face of death . . . they have detached themselves from

object-relationships to this world, and put their trust in another world, a
beyond. Freed from the menace of the superego.30
Psychoanalysis intentionally facilitates regression to allow a therapeutic opportu-

nity to rework developmental issues. ‘The couch’ is used as a trick to encourage
regression. Its emphasis is on emotions and not primarily cognitions. Similarly
in the dying when talking is no longer sustainable, ‘good enough’ mothering
(multidisciplinary caring) may provide such opportunities. The therapy becomes
‘play therapy’ in which the therapeutic tools are not toys but the everyday tasks
of life. Showering, toileting and making a patient comfortable are physical as well
as psychological interventions for the dying. Dependency and regression have
evolved pejorative connotations. Understanding the functions of these psycho-
logical mechanisms allows them to be therapeutically exploited.
Infantile dependency upon others who dominate and provide, creates ideal-
ising relationships with those who feed and protect. Palliative care workers are
often idealised by their patients. The desperate, regressed patient copes by plac-
ing faith in a parental figure, hoping for care and protection. A dying psychiatrist
wrote ‘like a child, I felt no shame at being bathed . . . dependency fears disap-
peared’.31 His nurse ‘knows everything; in a world that has become my universe,
she looms very large’.31
A therapeutic alliance was considered by Freud to be ‘an effective positive

transference’26 and Fenichel used the description ‘a rational transference’.26
Modern conceptualisation would refer to idealisation rather than transference
in this context. Transference is a repetition of past experiences, inappropriate
to the present.26 Freud considered it a ‘false connection’ between a person who
was the object of earlier (usually sexual) wishes and the doctor, which results
in substantial obstacles to treatment.26 This can occur during the final phase of
life, though the clinical relationship with palliative medicine is brief and barely
sufficient to start fermenting a transference relationship. Regression certainly
accelerates transference. Cognitive impairment limits transference from estab-
lishing. More likely it is the oncologist and not the palliative medicine doctor
who may be presented with glimpses of such interactions. Transference effects
may be positive and negative. The intense rage that the oncologist cannot, or will
not, save the patient may be wrapped in transference.
Parallel psychological reactions may be occurring in the supporting family. It
is in family members where transference issues may eventuate, often unbeknown
to the practitioner. At grief follow-up reviews these issues may surface.
APPEARANCE AND BODY IMAGE

A distorted body image or self-impression of our appearance is normal.32 There
is a discrepancy between image and reality. To see oneself in a photograph or a
video, to hear a tape-recorded message of one’s voice, is not exactly as expected.
Most, however, have reasonably accurate images of physical status and attributes.
The self-image is the core on which the sense of one’s identity is built.33 No baby
is perfect, except hopefully to its ‘good enough’ mother. The child relates to its
body in the same way in which its mother relates and related to it. These psycho-
logical processes evolve early, within the first 2 years, but continue to develop
with the evolution of language and communication until age 7–8 years. Self-love
and self-esteem rest on a positive self-image. The ego has primarily a bodily
frame, though its creation is multidetermined. The body image is constructed
out of the physical body that one has, and the experience with others that this
body has.32 The body image becomes the self-image through the process of
identification.34
Cachexia and the mutilating consequences of cancer savagely assault body
image. If fickle, as in adolescents and severe personality disorder patients, the
body image and self-esteem are challenged. Psychological regression enhances
this fragility. Culture and fashion influence what is considered to represent
beauty, which is usually considered as a visual attribute. Most of the human
brain is involved with visual function, and most stimuli are visual. The skin is the
largest organ and has the same embryonic origin as the nervous system, hence
the intimate relationship between sight and emotions. Illness may fragment
the ‘psychic envelope’ because it shatters the integrity of the physical interface
between patient and others.34 An attractive visual body image helps self-esteem,
particularly for women. The desire to be seen, to be looked at, is as inborn as the
desire to see.32 Health and beauty are assumed (incorrectly) to be related. The
preoccupation with slimness in the West, in its extreme state anorexia nervosa, is
matched by a preference for largeness in most other cultures. Both are only feasi-
ble options to the respective wealthy. The slimness of AIDS and cancer, however,
is not appreciated. The most visible physical defects are facial, the focal point of
communication. A blemish becomes an ‘anchorage point’, an ugly head or neck
cancer is ‘spread’ to form an unattractive person.33 ‘You are not looking well’ is
the most penetrating of health comments. Physical deformity evokes upsetting
feelings in others, who prefer to avoid the damaged individual. ‘Social death’ of
the physically unattractive is the extreme consequence. Shunned, shamed and
self-conscious, the scared and mutilated struggle to retain composure, dignity
and esteem. They fear alienation, rejection, and abandonment, and risk social
withdrawal, depression, and loss of identity.
Appearance ceases to be commented upon as the ravages of illness become
apparent. The individual avoids the mirror if possible and family learn to collude
and not to make mention of how they look. To the nursing and medical staff
grossly swollen abdomens and fungating ulcers are usually willingly presented.
This necrotic exhibitionism is important communication of physical status, but
also challenges psychologically the commitment to care of the staff. Eventually,
patients may regress ‘beyond privacy’. ‘There is something in sickness that breaks
down the pride of manhood’, suggested Charles Dickens (1812–70).35
DISGUST AND CARING
He was lame, and no-one came near him . . . to quiet the raging, bleeding,
running, in his maggot-rotten foot.
Philoctetes – Sophocles (496–406 BC)36
The skin is involved by metastases in 3–4% of malignant tumours. Malignant

fungating wounds are unsightly and smelly. They are humiliating and shameful
to the sufferer. The practice of palliative care involves acquaintance with disgust.37
Disgust literally means ‘bad taste’. It is evoked by repugnant smell, touch, sight
and hearing, and encourages recoil from the offensive stimulus.38 What consti-
tutes a disgusting stimulus varies among individuals and cultures.39 Disgust is
an emotion, and its function is to support survival by avoiding the dangers of
contamination or pollution. It is innate and ‘hard-wired’. There is also an alluring
component to disgust (e.g. horror movies), as if to keep the response practised.
Caring necessitates overcoming the disgust response.37 The recoil response

can be contained or muted by experience, custom and learning. There are a
multitude of coping strategies used such as mouth breathing, dissociative cogni-
tive strategies and intellectualisation. Familiarity eases the shocking revelation.
Clinical stoicism is the most important coping strategy. Health professions need
to transcend their disgust. To achieve intimacy with another, disgust needs to be
suspended. The rewards are considerable, and relationships with these patients
are rapidly cemented.37
BREAKING BAD NEWS

Deteriorating health involves a procession of ‘bad news’, of being presented the
information that stability or recovery is not occurring. This information allows
appropriate adjustment, both practical and emotional, so that the patient can
make necessary decisions about their future.40 Ascertaining the information
already known, what details are wished to be known, and titrating the medical
facts in language comprehensible to the patient, at a pace and in portions able
to be incorporated, requires tact and skill. Too much painful or technical infor-
mation results in muddled denial, too little risks unrealistic or false hopes. It is
the quality of the interaction, the respectful sharing of the information, and not
merely the time spent that is appreciated by patients, whom in palliative care
practice often have a sense that the news will not be pleasing. They may actually
be seeking objective clarification of their decline.
PSYCHOTHERAPY AND THE DYING
Words are, of course, the most powerful drug used by mankind.
Rudyard Kipling (1865–1936)41
The assumption that all cancer patients need therapy and that any type of therapy
is better than no therapy is unjustified. Psychologically healthy persons do their
own psychotherapy. It can be difficult to acquire a developmental history from
the dying for practical reasons, but also for the perception of the irrelevance
of such history. Identifying those in need of formal therapy can be difficult.
Contrary to public impression the vast majority of a population received ‘good
enough’ mothering and have the inherent psychological strengths to manage an
incurable illness.
Wrong words and poor therapy have negative side effects. Psychotherapy
undermines personal competency and coping strategies if these are intact and
capable. While eventually these initial side effects can be overcome and sur-
passed, time is a critical factor in the terminally ill. The relationship with the
primary medical caregiver is potentially the most important psychotherapeutic

tool.42 Active listening (listening with concentration, curiosity and empathy) is
required. Establishing a relationship, within the context of the delivery of medi-
cal care, not only is meaningful for the patient, it bonds them to the management
plan. A therapeutic alliance is formed, and psychological healing can begin.
Distress is not invariably pathological. It is also deceptive and can be hidden.
Assessment of psychological status is necessary, but should not always proceed
to therapy. Affirming normality in itself is therapeutic. Non-abandonment, a
central ethical obligation for doctors (and all staff ), is a core therapeutic com-
ponent of the professional relationship.43
There are as many styles of psychotherapy as therapists, but as infirmity
increases, options become more limited. Physical frailty and the inability to
sustain attention and concentration enforce the need to shift from formal-
ised, office-based styles of therapy. The psychological themes remain usually
unchanged, though they are often more starkly presented. The value of time
increases, and willing patients remove the psychological packaging and protec-
tions. Therapies, in general, promote active coping and/or explore emotions.44
As death approaches, insight-orientated therapy is too demanding and time is
too limited, cognitive–behavioural models likewise.44 But components of these
may be useful. Group therapies are not feasible. Existential therapies such as
logotherapy and meaning-centred therapy are particularly beneficial for those
struggling with morale.45 Life narrative therapies addressing the meaning of the
illness in the context of the life trajectory, especially if able to be written, are
valuable both for the present and for the survivors.46,47 Conserving personal and
social esteem by the creation of a legacy or generativity document, highlighting
past achievements and aspects of life considered potentially valuable to others,
becomes more difficult with increasing physical frailty. Protocol-reliant thera-
pies such as dignity therapy48 may require to be abbreviated towards the end of
life as communication abilities falter. Guided imagery can be a shortcut to the
psychotherapeutic.49
With further illness progression, briefer verbal interactions and enhanced
physical interactions eventuate. The topics of therapy narrow to the immediate
interpersonal relationships and the crisis of the loss of independence. Ironically,
the concepts of psychoanalytic psychotherapies become increasingly relevant
as talk fades and fundamental psychological issues become all-encompassing.50
Attachment insecurities, regressive transferences (and staff countertransfer-
ences), the temptation of professional boundaries to be eroded, the fears of dying,
and the loss of autonomy are issues eased by an understanding of psychoanalysis.
‘Good-enough mothering’ may facilitate a ‘good-enough death’. Sensory thera-
pies become increasingly attractive as talking therapies become obsolete. Verbal
reassurances can be substituted with touching affirmations. Massage, music,
aromatherapy, and ‘play’ therapies assume importance. They are accessible and
consistent with the regressive processes accompanying dying. The practitioners
of these therapies, usually nurses, often lack formal psychotherapy training.
Holding, both psychologically and physically, becomes a focus during the final
days. But skilled and experienced psychotherapists tend not to be able to aban-
don talking, and neither do they have the flexibility to offer frequent, brief or
opportunist psychotherapeutic sessions. The telephone is useful but also limited.
Committed therapists de-escalate therapy and continue some supportive contact
and liaison with the lead carers. Abandonment is not necessary. Saying goodbye
is not the same as ‘giving up’.44 The psychological intuitions of those working
with the dying are generally sound. Staff support, supervision and mentoring
are valuable for these and indeed all practitioners.
Similar issues concern the psychotherapeutic support of families. The chance
emergence of a therapeutic opportunity late at night needs to be addressed by
the nursing staff. Formally arranging a family therapy session is bound to be
countertherapeutic in such a situation.
STAFF BURNOUT
The practice of medicine is demanding and stressful. Inherently, no specialty is
more or less stressful than any other; the demands of attending patients threat-
ening to die but who usually don’t (psychiatry), is as stressful as working with
those who know they are dying and do (palliative medicine). The apprenticeship
to becoming a specialist is a long indoctrination. Gaining experience of medi-
cine and the medical lifestyle is a rigorous process. Doctors select or gravitate
to work within the specialties where they feel most at ease and function most
comfortably. Eventually, as the saying goes, a doctor inherits the practice he or
she deserves. All need holidays, and all workers tire and eventually burn out. The
symptoms of burnout are low-grade anxiety and affective ones, the consequences
being that work performance and enthusiasm falter. Rather than considering
the intrapsychic issues, the situational ones (i.e. the work) are conceptualised
as aetiologically relevant, hence the term ‘burnout’. While this may remove the
stigma of psychiatric illness and highlight the need for ‘time off ’, it does not alter
the required management of the individual.
Compassion (the work of healing and assisting) fatigues, life outside of work
is packed with life events, and collegial relationships are rarely always smooth.
Though increasingly medicolegally high risk, and tiresomely bureaucratic,
medicine remains a fascinating and usually rewarding occupation (or vocation).
Losing control of workload and professional autonomy, challenged by manage-
rial interference, are the most irritating and destructive aspects of the modern
consultant’s job. These stressors are more prone to inducing burnout than clini-
cal issues and demands. Hardiness is a valuable personality characteristic and
a necessary professional attribute.51 Self-awareness and self-care are practices

mitigating against burnout.52 In palliative care practice patients die, mutidiscipli-
nary teams fight, and each day distraught patients and families require empathy
and understanding. Caregiving is demanding. Working within personal and
professional boundaries is protective and preserving of the practitioner. No one
is immune to burnout, but neither should it be expected or anticipated because
one works with the dying. Rates of burnout in palliative care, possibly about 25%,
are lower than in other specialty areas.53 This is probably due to the higher profile
of this consequence of dedication to work in palliative care.
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15 Holdcroft C, Williamson C. Assessment of hope in psychiatric and chemically depend-
ent patients. Appl Nurs Res. 1991; 4: 129–34.
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14: 36–42.
17 Kwon P. Hope and dysphoria: the moderating role of defense mechanisms. J Pers. 2000;
68: 199–223.
18 Fromm E. The Revolution of Hope: towards a humanized technology. New York: Harper
& Row; 1968.
19 Roethke T. In a dark time. In: The Collected Poems of Theodore Roethke. London: Faber
& Faber; 1968. p. 239.
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21 Kylma J, Vehvilainen-Julkunen K, Lahdevirta J. Hope, despair and hopelessness in liv-
ing with HIV/AIDS: a grounded theory study. J Adv Nurs. 2001; 33: 764–5.
22 Lamb C. The convalescent. In: The Essays of Elia. London: JM Dent & Sons; 1906.
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23 Noyes R Jr, Clancy J. The dying role: its relevance to improved patient care. Psychiatry.
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24 Abiven M. The crisis of dying. Eur J Palliat Care. 1995; 2: 29–32.
25 Balint M. Primary narcissism and primary love. Psychoanal Q. 1960; 29: 6–43.
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27 Kimsey LR, Roberts JL, Logan DL. Death, dying, and denial in the aged. Am J
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29 Ploye PM. A note on two important aspects of Kleinian theory: ‘projective identifica-
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expressions of disgust. Nature. 1997; 389: 495–8.
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46 Byock IR. The nature of suffering and the nature of opportunity at the end of life. Clin
Geriatr Med. 1996; 12: 237–52.
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52 Kearney MK, Weininger RB, Vachon MLS, et al. Self-care of physicians caring for
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1155–64.
52 Vachon MLS. Staff stress in hospice/palliative care: a review. Palliat Med. 1995; 9:
91–122.
CHAPTER 4
Families and caregivers
No man is an Island, entire of it self.
John Donne (1572–1631)1
Spouses, partners, children, extended family, friends, colleagues and caregiv-

ers are all affected by an individual’s terminal illness. Families may be headed
by a married couple, they may be blended, single-parent or same-sex families.
The ‘legal’ family may not be the ‘social family and carers’ depending upon
whom is considered significant and committed to the group. Irrespective of
the make-up, all members experience grief, distress and disruption by a severe
illness of another member. Symptoms of strain and negative mental health
outcomes are reported in at least 40% of significant others of patients dying
from cancer.2 In family caregivers provided a self-report questionnaire follow-
ing admission of their relative to a palliative care service, 44% were suffering
anxiety and depressive symptoms, 15% met criteria for pre-loss grief, and 10%
reported demoralisation.3 This distress often goes unrecognised. The crisis of
dying is shared by the individual’s ‘support team’. The burdens and pleasures of
care are distributed among the individual’s social network, who grieve, protest,
despair, acknowledge and adjust as the inevitability of death becomes apparent.
The cohesion and resilience of relationships may be sorely tested, social bonds
may be stretched and/or strengthened. The experience can threaten a family’s
survival. The empathic support of palliative care professionals is a crucial influ-
ence on how families may adapt and cope. The family becomes an integral part
of the multidisciplinary team during the final journey.
The experience of caring for the terminally ill may also precipitate or unmask
psychiatric illness in the caregiver. Prevalence rates are reported of 3.5% for
generalised anxiety disorder, 8% for panic disorder, 4% for PTSD and 4.5% for
major depression.4 These may be conservative figures, for to date this literature
is scanty. In family caregivers perhaps 20% are ‘highly likely’ to have an anxiety
39
disorder and 10% a depressive disorder.3 Men whose partner have a diagnosis
of breast cancer are at increased risk (at a hazards ratio of 1.39) for hospitalisa-
tion with a severe affective disorder, and after the death of the partner they have
a 3.6-fold increased risk.5 While there may be multiple influencing factors, not
surprisingly, caring for the sick is demanding and challenging to mental health.
And while the health-professional headlights need to be on the dying, the park-
ing lights should be focused on the caregivers.
GRIEF AND BEREAVEMENT
Grief is itself a med’cine.
William Cowper (1731–1800)6
Attending to the bereaved (those whom are in a state of loss resulting from
death), is a responsibility of palliative care. Grieving begins at diagnosis. Grief is
the distressing emotional response initiated by the death of a loved and attached
person, or indeed any significant loss. It is not pathological but a normal process.
Sadness, anger, distress, tearfulness, insomnia, pining and haunting reminis-
cences about the deceased are typical symptoms. Waves of distress, the pangs
of sadness, often cued by reminders and reminiscences, characterise grieving.
In the intervening periods normal functioning occurs. Yearnings for the lost
one often trouble the grieving. Not infrequently, the bereaved may experience
fleeting auditory or visual pseudo-hallucinations of the deceased and perhaps
a sense of presence. These sometimes unsettling experiences are more likely to
occur during moments of quietness and relaxation. Over time the distress, sad
mood and negative cognitions fade in intensity and frequency. Culture and social
norms are important determinants as to how grief is expressed. Mourning, the
process of adaptation, incorporates the cultural and sanctioned social rituals of
the community. As families grieve the cumulative losses accompanying serious
illness they may simultaneously mourn the impending death. Mourning typi-
cally begins before loss. The length of mourning is proportional to the strength
of attachment to the lost person. Bonding breaks and separations, particularly if
permanent, are emotionally painful. Outbursts of wailing, the wearing of appro-
priate clothing, the funereal rites and customs associated with death and dying
vary throughout the world. The common custom of wearing black and women
donning a veil after death probably stemmed from the desire to conceal the
identities of the mourners from any malevolent spirits lurking about the grave.
Whatever the mourning customs may be, they serve to organise, protect and
support the grief-stricken. If not respected and nursed, grief may become com-
plicated. The disruption to the flow of life after a loved one’s death is transient.
FAMILIES AND CAREGIVERS 41
Specific stages of mourning needing to be traversed have been proffered, but

not confirmed. Our losses are never irretrievably forgotten. Grief is never fully
resolved.
The understanding of the irreversibility of death is age specific. Most children
have not developed the capacity to appreciate the permanency of death until
aged 9 to 10 years. The child may place the deceased in ‘heaven’, hopeful of a
return. This should not dissuade open discussion and participation in the ritu-
als of mourning, but does demand an understanding by adults that this is not
an abnormal conceptualisation. Young children may blame themselves for the
death, believing a minor misdemeanour they conducted caused it. Conversely,
the apparent simple acknowledgement of the death of a life partner by an elderly
widow does not indicate relief but more likely an acceptance of the natural life
cycle. That widowers tend to remarry soon after the death of a spouse, often
within a year or so, whereas widows tend not to, may be related to influences
other than maladaptive grief.
Complicated grief
If grief is intense and/or protracted after 1–2 years has elapsed, the process is gen-
erally considered to be morbid. This may occur in 10% to 20% of the bereaved,7
and is more likely if the death was sudden, unexpected, or traumatic and if
the relationship had been one of intense dependency or ambivalence. Queen
Victoria, abruptly widowed at a relatively young age, lived her long life clouded
by her protracted grief reaction. Grief is a dynamic process. If it gets stuck,
more expert psychotherapy and pharmacotherapy may be indicated. Those
with psychological and psychiatric vulnerabilities and who are socially isolated
or alienated are at greater risk. Severe and prolonged grief may be indicative of
comorbid depression, substance abuse or other compounding psychiatric illness.
If the tincture of time and support is not reshaping grief after several months,
consideration of a coexistent psychiatric illness should be made. A psychiatric
illness in remission may be activated by the loss of the person and their support.
Disenfranchised grief refers to the hidden grief of those socially unable to express
their response. A secret or ostracised mistress or confidant may be excluded from
the family’s mourning rituals.
Management of grief
We live in a death-denying and death-defying society; few are well prepared.
Good bereavement care commences well before the patient’s death. Theoretically,
anticipatory grieving might be expected to mitigate the intensity of mourning,
though findings are inconsistent. Incorporating ‘death talk’ into routine medical
and nursing care may pre-empt and prevent some of the risk factors for difficult
grief reactions. Early identification of those at high risk of complicated grief
allows the prospect of prompt interventions. Even if not wishing or needing spe-
cific engagement, relatives are generally appreciative of the interest and offer, the
expression of care and remembrance. Comfort in managing grief is an essential
skill for all who work in palliative care.
Death always comes as a ‘shock’, even for relatives who have observed the
inevitable decline and are aware of the proximity of death. The medically
imprecise prospective determination of timing of death limits the ability to
confidently forewarn, even in hospice settings. Reality is sobering. Patient lis-
tening, support and guidance over medicolegal and funereal arrangements are
appreciated during the initial acute shock. Short-term use of benzodiazepine to
ensure sleep is occasionally helpful. Cohesive and competent families need lit-
tle or no professional intervention. Chaotic and conflicted families may require
specialist psychological and psychiatric care, as may the isolated and lonely sur-
vivors. Offering information, support, and if necessary counselling, is a key task.
Permitting and normalising the distress of grief, reassuring sanity, directions of
how to proceed (e.g. contacting an undertaker, consulting a lawyer) and being
open to talk ‘death’ help validate the process. Individuals need to ‘work through’
their feelings and severe their bonds with the deceased. Cathartic expressions of
grief are of little therapeutic value unless combined with cognitive reappraisal.
Adaptation to loss and reconstructing a world without the physical presence
of the deceased are core tasks of grief, which is a cruel but effective medicine.
Despite the emotional pain of grief, it demands of the individual psychologi-
cal creativity in order to ‘replace’ the loss with ‘live’ memories of the deceased.
Intrapsychically, the lost person, if significant, is able to be forever recalled. Life
may be a procession of losses, however these vicissitudes of life also serve to
entice psychological growth, maturity and wisdom.
Bereavement follow-up is crucial, particularly for those at high risk. Normality
and resilience should be respected but grief for a few may become nasty.
Palliative care services generally offer telephone and/or personal follow-up visits
over the initial lonely few months and perhaps at the anniversary date. Specific
grief counselling, if indicated, tends to be of brief duration, focused on empathy,
coping, cognitions, and pragmatic reintegration into society. If spiritual issues
are relevant, chaplaincy assistance is advisable. An evidence base to support
grief counselling is lacking. Over-pathologising the bereaved is inappropriate.
Ignoring the bereaved, particularly if well-known past ‘team members’ of the
palliative care service, is also inappropriate. Staff forget the names of their dead
patients, but not the person (or their carers) and the unique health complications
or circumstances. Though the professional attachment may have been relatively
brief, it still deserves to be mourned. This needs to be a component of staff self-
awareness and self-care.
PSYCHOSOCIAL SUPPORTIVE CARE

Strengthening relationships with loved ones has been identified by patients
with terminal illness as an important facet of end-of-life care.8 Indeed emo-
tional, relational and spiritual issues may be of greater concern to seriously ill
patients and their caregivers than physical symptoms and medical interventions.9
Practical, informational and emotional help are the most important forms of
social support.10 Emotional support is appreciated by 80% of people with cancer,
informational support (if provided by healthcare staff ) is valued by 41%, and
practical support needed by 6%.11 With illness progression and dependency the
need for practical assistance increases towards that of the emotional supportive
needs. For some families being taught to provide basic nursing cares to a dying
relative can be most gratifying and emotionally affirming of them. People with
cancer are frequently disappointed with the perceived quality and level of sup-
port they receive.10 This may be a reflection of a regressed and insatiable need
of ‘mothering’ in the face of calamity, though may also be a reality in the busy,
family fragmented modern world. Yet every individual has differing needs and
each family is a unique social group with varying skills and attributes. Some show
little ability to attend to practical or physical needs of the patient, some are so
emotionally overwhelmed or restricted that they are inadequate in this regard,
and some may deny or collude with factual aspects of the illness and are thus
unable to provide informational support. Every family has strengths, though
they may only be discovered by the adversity and with the coaxing of attending
health professionals.
Family meetings poignantly portray family pathology as well as family
attributes. A ‘normal’ family does not exist. The key dimensions of family func-
tioning are ‘cohesiveness’, ‘adaptiveness’ to conflict, and ‘expressiveness’.12 Mutually
supportive families, able to communicate freely and resolve conflict, are the least
vulnerable to disintegration in the face of a crisis such as severe illness. A family’s
collision with doctors withholding the medical details from the patient, is not an
uncommon phenomenon in many non-Western cultures, and though intended to
be protective, is rarely actually so.13 Though some patients do not want to know
medical information, or prefer to deny it, few if any don’t recognise the gravity
of declining health. Early recognition of troubled families and dysfunctional
communication is clearly beneficial and often patently apparent in the early
stages of the patient’s disease. Families also regress in response to threat, they
stiffen and retrench – a family in crisis may not always portray their strengths.
Chaotic families tend to induce more disruption in crisis. Assessment of family
dynamics becomes crucial if the sick are to be cared for in the community. The
effectiveness of family interventions is uncertain. ‘Focused family grief therapy’
(FFGT) holds promise for ‘hostile’, ‘sullen’, and incohesive families by focusing
and strengthening these key dimensions of family functioning.14 Encouraging
the expression of emotion, providing answers to questions, simply reframing

some of cognitive negatives, and acquiring some historical and future perspec-
tive of the family may all be of benefit while the family endures the upheaval of
losing a member.
Dying in one’s own home is the preference of many, estimated to be between
56% and 74% of the population of the UK,15 and is an intention supported by
palliative care services. However, this may not occur. Over recent decades, dur-
ing which time palliative services have expanded, the numbers of those dying
at home has decreased. Between 1974 and 2003 the proportion of home deaths
in England and Wales fell from 31.1% to 18%.16 In developed countries only
approximately 25% of patients actually have a home death.17 This figure will be
very much higher in less developed countries where other care options may not
exist. Up to a third of those patients who died in hospital rather than at home
could be have been managed in the community if excellent end-of-life services
were in place.18 Restricted services is undoubtedly an influence, but also may be
the disparity between the choice of an individual and the ability of families to
care for them in the home. With adequate professional support many families
could cope more effectively. Exhausted families regretfully depositing the dying
in hospice care for the last few days may be a reflection of the insufficiency of
psychosocial support provided for them. For some caregivers the fears associ-
ated with the final phase of life may be too great, for others (particularly Asian
cultures) dying in one’s own bed may be superstitiously unacceptable. Such
reluctance might be surmounted by attentive counsel and support, especially if
this is introduced early, is consistent, and is validating to those caring.
A critical, and undervalued, component of community palliative care is the
augmentation of physical care with psychosocial care. Utilising a solid and secure
treatment alliance, often established through physical cares, community pal-
liative care staff are ideally placed to gently commence addressing the relevant
emotional issues. Unlike earlier generations, modern Western families may have
little or no exposure to dying and death. Families survive terminal illness and
incorporate the experience, good or bad, into their history. Their experience
and awareness of dying may be the catalyst for major psychological matura-
tion and a spark that enlivens a generation. Stressful and potentially harmful to
mental health, as it is, caregiving for the dying can also be a positive experience
for a family.
SPOUSES AND PARTNERS

The shocks of diagnosis, treatment and illness complications, and progression
are shared with those who are most intimate. When one member of a couple
develops a life-threatening illness, the lives of both partners will be changed.
Challenges include how communication is affected, role and responsibility
changes, coping and adjusting to the rigours of disease, and ultimately, and often
the most difficult stressor, the dying. Perhaps the most important of the risk
factors for partner distress are relationship factors, such as the level of marital
satisfaction and the quality of family functioning.9 Insecure, unstable, and emo-
tionally distant marriages are rarely able to withstand a severe medical illness
within it. Secure, confiding relationships serve as a buffer against psychological
distress and depression.19 The level of support spouses provide to one another is
a strong predictor of adaptation and health outcomes in cancer, particularly if the
relationship is characterised by emotional expression and cohesion.20 The degree
of attachment is the critical component of a secure marital bond. Attachment and
caregiving styles are closely linked, and are predictive of marital satisfaction.21
Secure attachment tends to be associated with highly responsive care.22 Severe
illness, hospitalisations, changing roles, and carers’ respites create separations,
and even the most robust relationships are rocked by attachment stressors.
Relationships are strained and existing problems are exposed and aggravated.
Most studies indicate that patients and their spousal caregiver have similar levels
of distress, and that this increases as death approaches.9 However, the particular
stressor is obviously different for each person. Every individual processes these
in distinct ways and at differing times. Psychological adjustment to declining
health can rarely occur in unison. Parallel grieving is unsustainable and usually
the patient is permitted to react initially. For some it is not till after the death of
their partner that the opportunity to reveal their emotions is possible.
Patterns of marital communication are critical to the progress of the rela-
tionship through the cancer journey. Communication is not merely verbal
interchange but the multimodal currency of interpersonal relating. Seemingly
pragmatic interactions can be profoundly revealing. A gentle hand to prevent a
fall may be an expression of fondness, or over-solicitous caring, the atonement
for guilt or a defence against repulsion. Encouraging food in a forlorn attempt
to reverse cachexia might be a loving act, a cultural obligation, or a lack of
appreciation of the proximity of death. Enforcing activity and function, despite
vital exhaustion, may have noble intent but be medically cruel. Appropriate
and ‘good-enough communication’ is difficult to sustain through crises, par-
ticularly if the relationship is previously fraught and frail. Open, confiding
communication between partners, as well as with the palliative care team, augers
well. Women tend to be more emotionally in tune and self-disclosing than are
men.10 Female distress is often more apparent. Males may bury their distress in
work, alcohol, and denial. Women may turn to women friends for support and
away from their seemingly uncaring partner. Partners may resent the copious
attention provided to their loved one, and crave that their unmet needs be rec-
ognised. Communication may be contaminated by the projection of anger onto
the other, by fatigue blunting the capacity to interact, and by the re-emergence
of developmental insecurities. The partner may cope by offering bravado and

hopeful reassurances, by critical and assertive advocacy, by negative withdrawal
and avoidance, or by postponing their own emotional reactions (sometimes
until after the death). Probably the most insidious and unhelpful response is
insistence upon ‘positive thinking’, the maintenance of a mental straight-jacket.9
Talking (including ‘death-talk’), sharing, reminiscing, planning for the future,
and regretting, are healthier responses. The ability of a couple to ‘hold’ each
other’s distress, and not to catastrophise or overreact, usually an indication of
attachment security and maturity, is important.23
Employment, financial and practical changes in lifestyle are inevitable seque-
lae of serious illness. Physical limitations force alterations of routines and roles.
Women may need to put out the rubbish bins, and men shop for groceries.
Sexual problems are common and though the importance of sexual physicality
in relationships varies, sex is an important factor in the quality of life of patient
and partner.24 Fears of being physically hurt, the embarrassment of surgical
mutilation, prostatic impotency, the disgust of colostomies and catheters, the
desiccating adverse effects of medications, and the weakness and shame of ill-
ness impact upon libido and performance. The healthy partner may perceive
rejection, the disinclined unhealthy partner the humiliation of sickness. Some
couples wish to explore new strategies of touching and connecting, and all need
to evolve intimate alternatives, sometimes these needing to be purely psycho-
logical. Assumptions about sexuality are notoriously incorrect. Most couples, on
direct questioning, are willing to convey the relevance of their sexuality to the
current predicament.
Positive mental health outcomes are also possible. Relationship growth
may occur during the last phase of life and psychosocial care at this juncture
may ease the bereavement process and better prepare the survivor for their
future.9 Professional support can guide the couple through the rocky passages.
It is uncharted waters for the couple; an external navigator can be invalu-
able. Observation, interpretation and monitoring by staff instructs if or when
assistance may be required. Enhancing and validating the coping skills of the
partner, protecting battered esteems, providing respite and relief, and refereeing
disputes are crucial therapeutic tasks. There is a small body of evidence on the
effectiveness of couple interventions for those where one is in palliative care.9
Behavioural, emotionally expressive, and interpersonal couple therapies, though
lacking as yet firm, evidence-based support, appear to be beneficial.9 A crucial
step in management is identifying the problems and inviting assistance from
those with psychosocial expertise. Attention to the attachment bonds and com-
munication of couples are the obvious therapeutic foci.
THE CHILDREN OF THE DYING

Children are quick to sense a crisis, and notice changing events within the
family. The deteriorating health status of a parent can’t be masked from chil-
dren. Parental cancer has a significant impact on the whole family system.
Children experience emotional, behavioural, social, physical and cognitive
consequences.25 Their sense of security is assaulted. Alterations in the behaviour
of a child, particularly uncharacteristic ‘bad’ or oppositional behaviours, may be
indicative of distress. Depending on developmental age a child may be unable
to articulate a specific question, or they may be too fearful to dare. Children are
liable to catastrophise, or perhaps somehow blame themselves for the parental
health misfortune. The most at-risk children to develop psychosocial problems
are adolescents who may recognise the gravity of the situation and may well be
confronted with practical, psychological and social demands consequent upon
the parental illness. This is particularly the case for adolescent girls, perhaps
because of their pre-existent and expected caring roles within the family.
Informing children reduces their anxieties and concerns.10 Determining the
occasion and manner of the revelation of the illness crisis to children is a parental
obligation. Parents know their children best. However, the parent or parents may
benefit from reassurance and the guidance of health professionals at this time.
The provision of age-appropriate informational literature, advice regarding sim-
ple terminology and phrasing, and the support of those breaking the bad news
is helpful. Though the child ‘knows’ something is amiss, informing them is not
an easy parental task. Most children indicate relief, for most have actually fanta-
sised a more calamitous crisis. The modern medical conversion of cancer from
an acute fatal illness to a chronic one has, however, complicated this issue. The
risk with long-prognostic illnesses, such as prostate and breast cancers, is that
the child’s developmental progress can be hampered by the ‘sword of Damocles’.
Reluctance to express playful or adolescently oppositional behaviours towards
the sick parent may impede the attainment of various milestones. Other children
may assume a pseudo-mature attitude of responsibility and an unnecessary obli-
gation to care for the ill parent, at the expense of their own peer-group activities.
Yet withholding information may be harmful in other respects. Deciding how
much information to reveal, and when, is ultimately an intuitive decision on
the part of the guardians. Most children are sufficiently robust and resilient to
incorporate knowledge of parental frailties and illness, though some do require
specialist mental health expertise. Siblings of child cancer patients are at risk for
developing emotional, behavioural and social problems. They may feel neglected,
guilty for being healthy, responsible for somehow ‘causing’ the illness, and grief-
stricken. They too may require expert mental health assistance.
CAREGIVERS’ BURDENS AND BENEFITS

Caregivers may be family members, volunteers or paid workers. It is not an
easy job, and though time-limited (in palliative care), it may require months of
dedicated commitment. Seventy per cent of caregivers are female.10 Professional
caregivers are generally poorly paid, long-suffering, and underappreciated.
Family members and friends who fulfil caregiving roles can be exhausted by
their own complex emotional predicament. If care in the community is feasible,
caring for caregivers is critical and it is often neglected within the ‘business’ of
modern healthcare. Amid the drama of the sick bed the carer can easily become
forgotten, the ‘hidden patient’.26
The impact on the caregiver’s quality of life varies along the illness trajec-
tory (and afterwards), dependent upon the crises and complications endured,
but tends to increase in the latter stages.27 The personal tasks of feeding and
toileting are most burdensome, the non-personal tasks such as shopping and
transportation are the easiest, and the emotional support the most difficult.10 Not
surprisingly, relatives caring for patients in the late palliative phase suffer from
great fatigue.28 Other health risks to caregivers include anxiety, sleeplessness,
weight loss, depression, burn out, and a general deterioration in health.29 Some
family caregivers adapt, and some wear out.26 The relationship between carer
and patient (and family) is a key component to the durability of the caregiver’s
assignment. It is often the lack of practical support with respect to the provi-
sion of physical cares that caregivers most need assistance with to sustain them
in their challenge.30 Preparatory educational groups for caregivers have been
shown to be accessible, applicable and effective.29 Respite, ‘mental rest’, exercise
and recreation, and psychosocial supports are needed for the caregivers to fulfil
their journey.
Though stressful at times, caring for the terminally ill can be immensely satis-
fying. For some it is a rewarding vocation, for others the experience of caring for
a terminally ill relative remains a gratifying memory. About 10% of an Australian
metropolitan population have provided hands-on care for a dying relative.31 A
proportion of these, 7.4%, indicated on review that they would not take on such
a role again, and 16.5% said that they probably would not.31 This suggests that
caregiving for some is a once-in-a-lifetime event. It also raises the question as to
whether or not additional support by palliative care expertise may have allowed
them a less arduous experience.
REFERENCES
1 Donne J. Devotions upon Emergent Occasions. Meditation XVII. (1623). In: The Works
of John Donne, Vol. 3. Alford H, editor. London: John W Parker; 1839. pp. 574–5.
2 Ostlund U, Wennman-Larsen A, Persson C, et al. Mental health in significant others
of patients dying from lung cancer. Psychooncology. 2010; 19: 29–37.
3 Hudson PL, Thomas K, Trauer T, et al. Psychosocial and social profile of family caregiv-
ers on commencement of palliative care. J Pain Symp Manage. 2010; 41: 522–34.
4 Miovic M, Block S. Psychiatric disorders in advanced cancer. Cancer. 2007; 110:
1665–76.
5 Nakaya N, Saito-Nakaya K, Bidstrup PE, et al. Increased risk of severe depression in
male partners of women with breast cancer. Cancer. 2010; 116: 5527–34.
6 Cowper W. Charity (l. 159). In: The Oxford Book of Quotations. 3rd ed. London: Book
Club Associates; 1981. p. 164.
7 Prigerson HG, Vanderwerker LC, Maciejewski PK. Prolonged grief disorder as a men-
tal disorder: inclusion in the DSM. In: Stroebe MS, Hansson RO, Schut HA, editors.
Handbook of Bereavement Research and Practice: 21st century perspectives. Washington,
DC: American Psychological Association; In press.
8 Field MJ, Cassel CK. Approaching Death: improving care at the end of life. Washington:
National Academy Press; 1997.
9 McLean LM, Jones JM. A review of distress and its management in couples facing end-
of-life cancer. Psychooncology. 2007; 16: 603–16.
10 Brennan J. Cancer in Context: a practical guide to support care. Oxford, New York:
Oxford University Press; 2004.
11 Dunkel-Schetter C. Social support and cancer: findings based on patient interviews
and their implications. Journal of Social Issues. 1984; 40: 77–98.
12 Kissane DW, Bloch S. Family Focused Grief Therapy. Philadelphia, PA: Open University
Press; 2002.
13 Chaturvedi SK, Loiselle CG, Chandra PS. Communication with relatives and collusion
in palliative care: a cross-cultural perspective. Indian J Pall Care. 2009; 15: 2–9.
14 Kissane DW. A model of family-centered intervention during palliative care and
bereavement: focused family grief therapy (FFGT). In: Baider L, Cooper CL, Kaplan
De-Nour A, editors. Cancer and the Family. Chichester: Wiley; 2000. pp. 175–97.
15 Department of Health. The English End-of-Life Care Strategy. UK Department of
Health; 2008.
16 Gomes B, Higginson I. Where people die (1974–2030): past trends, future projections
and implications for care. Palliat Med. 2008; 22: 33.
17 Hunt R, Fazekas B, Luke C, et al. Where do patients with cancer die in South Australia,
1990–1999: a population based review. Med J Aust. 2001; 175: 526–9.
18 Abel J, Rich A, Griffen T, et al. End of life care in hospital: a descriptive study of all
inpatient deaths in one year. Palliat Med. 2009; 23: 616–22.
19 Hedgeson VS, Cohen S. Social support and adjustment to cancer. Health Psychology.
1996; 15: 135–48.
20 Burman B, Margolin G. Analysis of the association between marital relationship and
health problems: an interactive perspective. Psychol Bull. 1994; 112: 39–63.
21 Freeney JA. Attachment, caregiving, and marital satisfaction. Pers Relatsh. 1996; 3:
401–16.
22 Freeney JA, Hohaus L. Attachment and spousal caregiving. Pers Relatsh. 2001; 8:
21–39.
23 McWilliams AE. Couple psychotherapy from an attachment theory perspective: a case
study approach to challenging the dual nihilism of being an older person and someone
with a terminal illness. Eur J Can Care. 2004; 13: 464–72.
24 Mercadante S, Vitrano V, Catania V. Sexual issues in early and late stage cancer. Support
Care Cancer. 2010; 18: 659–65.
25 Visser A, Huizinga GA, van der Graaf WTA, et al. The impact of parental cancer on
children and family: review of the literature. Cancer Treat Rev. 2004; 30: 683–94.
26 Kristjanson L, Aoun S. Palliative care for families: remember the hidden patients. Can
J Psychiatry. 2004; 49: 359–65.
27 Kim Y, Given BA. Quality of life of family caregivers of cancer survivors: across the
trajectory of the illness. Cancer. 2008; 112(Suppl.): 2556–68.
28 Carlsson ME. The significance of fatigue in relatives of palliative patients. Palliat
Support Care. 2010; 8: 137–42.
29 Hudson P, Quinn K, Kristjanson L, et al. Evaluation of a psycho-educational group
programme for family caregivers in home-based palliative care. Palliat Med. 2008; 22:
270–80.
30 Bee PE, Barnes P, Luker KA. A systematic review of informal caregivers’ needs in
providing home-based end-of-life care to people with cancer. J Clin Nurs. 2009; 18:
1379–93.
31 Currow DC, Burns C, Agar M, et al. Palliative caregivers who would not take on the
caring role again. J Pain Symptom Manage. 2011; 41: 661–72.
CHAPTER 5
Psychiatry, spirituality and

palliative medicine
Simon Dein
Psychiatry and spirituality are closely tied together in the palliative care context.
A diagnosis of life-threatening illness often raises existential concerns such as
‘Why me?’ or ‘What have I done to deserve this?’ Patients may have difficulty
finding meaning in their suffering and their relationship with God might be
called into question (how could God allow this to happen?), even to the extent
that they lose their faith. Issues frequently arise about death and dying, and
patients often seek reassurance about the existence of an afterlife. Spiritual
issues about meaning can significantly impact upon mood.1 Though patients
might discuss these spiritual concerns with doctors, these health professionals
frequently lack the confidence to answer these questions and refer them to cler-
gymen. However, a full spiritual assessment of the patient is essential and should
ask what the illness means to them and whether there are any issues relating to
God or dying.
In this chapter I shall address a number of issues related to spiritual aspects
of death and dying: the difference between religion and spirituality, spiritual
distress and its psychiatric repercussions, the assessment of spiritual coping
strategies and the role of religious professionals in the management of spiritual
distress in the palliative care setting. I emphasise that it is incumbent upon all
health professionals to assess spiritual distress and coping and to be aware of the
resources available to manage this.
RELIGION AND SPIRITUALITY

By now there is a substantial body of literature examining the differences between
religion and spirituality. Some patients may define their problems as spiritual
rather than religious; by ‘spiritual’ they generally mean a transcendent relation-
ship between the person and the ‘higher being’ – ‘a quality that goes beyond a
51
specific religious affiliation’.2 The term ‘religion’ refers to ‘adherence to the beliefs
and practices of an organised church or religious institution’.3 Although spiritual-
ity and religion are often seen as synonymous, there are important distinctions
between these two constructs. Spirituality can exist both within and outside of
a religious framework, and many individuals who consider themselves quite
spiritual may not adhere to any particular religion. It is possible to be spiritual
without being religious but the reverse generally does not hold. Some may speak
of a connection to a personified God, for others the relationship is more abstract
– to the cosmos, or for some to nature generally. There is much debate about how
spirituality is defined. The experience of spirituality is different for each individ-
ual, and it is discussed and displayed differently between cultures.4 Between 50%
and 95% of cancer patients view religion/spirituality as personally important and
experience spiritual needs, particularly minority-group patients.5–8
SPIRITUALITY AND MENTAL HEALTH

The emerging literature suggests that aspects of religion/spirituality may provide
effective coping strategies for dealing with the symptoms of life-threatening
and terminal illness. More recent studies of religion and depression have used
more sophisticated methods, including validated, multidimensional measures
of religiosity. Unlike the literature on religion and depression, studies of spiritu-
ality and depression have been relatively scarce. One study using the Intrinsic/
Extrinsic Religiosity Scale found a strong negative relationship between religios-
ity, spiritual well-being and depression in a sample of 100 elderly patients with
cancer.9 Another study suggests that the beneficial aspects of religion in advanced
cancer may be primarily those that relate to spiritual well-being rather than to
religious practices per se.10
Overall spiritual well-being and quality of life are closely related among dying
patients.11 Spiritual well-being offers some protection against end-of-life despair
in those for whom death is imminent.12 The support of terminally ill patients’
spiritual needs by the medical team has been found to be associated with greater
hospice utilisation and, among high religious copers, less aggressive care at the
end of life.13
SPIRITUAL DISTRESS AND DEMORALISATION

The physical deterioration in the last stages of life may be associated with loss
of independence, dignity, autonomy and selfhood; these losses (or anticipated
losses) can result in significant emotional distress. Spiritual pain has been
defined as ‘pain caused by extinction of the being and meaning of the self ’ and
is characterised by three areas of potential loss – as a being founded on tempo-
rality, a being in relationship and a being with autonomy. The attempts to assess
these perspectives make it easier to talk with the patients about their spiritual
PSYCHIATRY, SPIRITUALITY AND PALLIATIVE MEDICINE 53
pain.14 Spiritual distress is commonly associated with negative religious coping

including beliefs about punishment or abandonment by God, and may impact
negatively upon mental well-being and quality of life.15
The construct of demoralisation is closely tied to that of spiritual pain and is
characterised by an inability to cope alongside feelings of helplessness, mean-
inglessness, subjective incompetence and diminished self-esteem. It differs from
depression, which typically is associated with anhedonia; this is not usually
present in demoralisation. The demoralisation syndrome is characterised by
loss of hope, loss of meaning and existential distress and is commonly found
in palliative care settings.16 At times, it can be difficult to distinguish spiritual
distress from agitated depression and if there is doubt a trial of an antidepres-
sant is warranted.
One study evaluated participants’ intensity of spiritual pain, physical pain,
depression and intensity of illness, with a qualitative focus on the nature of
patients’ spiritual pain and the kinds of interventions patients held would amelio-
rate their spiritual pain. Ninety-six per cent of the patients reported experiencing
spiritual pain but expressed it in diverse ways, as an intrapsychic conflict, as
interpersonal loss or conflict or in relation to the divine. The intensity of spiritual
pain was correlated with depression, but not with physical pain or severity of
illness and did not vary by age, gender, disease course or religious affiliation.17
Given both the universality of spiritual pain and the multifaceted nature of such
pain, when patients report the experience of pain, more consideration should
given to the complexity of the phenomena and that spiritual pain be considered
a contributing factor. Unaddressed spiritual pain may impede recovery and
accentuate the overall suffering of the patient.
THE ASSESSMENT OF SPIRITUALITY

There is increasing evidence that patients desire physicians to enquire about their
spiritual and religious beliefs when they are ill. However, a number of studies
indicate that spiritual issues are rarely addressed by Western physicians.18–22
A family practice study examined whether patients felt that physician enquiry
about spirituality or religious beliefs was appropriate, reasons why they wanted
their physicians to know about their spiritual beliefs, and what they wanted phy-
sicians to do with this information. Eighty-three per cent of respondents wanted
physicians to ask about spiritual beliefs in at least some circumstances includ-
ing serious medical conditions (74%) and loss of loved ones (70%).23 Patients’
willingness to discuss spiritual issues may depend on a number of factors: their
sense of physicians’ respect for their spiritual views, attitudes about spiritual
health, and qualities of openness and approachability.24
There is some data suggesting that physicians might perceive spiritual enquiry
to be useful.25 A practical, evidence-based approach to discussing spiritual
concerns in a form suitable to a physician–patient relationship may improve the

quality of the clinical encounter.26 Such issues may not, however, be readily asked
about in a usual clinical encounter and clinicians may find such discussions
threatening, particularly when patients’ religious affiliations and preferences may
differ from physicians’ or are unknown. Other barriers have been reported in the
literature including: lack of comfort or training, lack of spiritual awareness, fear
of inappropriately influencing patients, discomfort with initiating discussions,
lack of concordance between physician and patient spiritual or cultural posi-
tions, no common ‘spiritual language’, fear that it’s wrong to ask doctor spiritual
questions, belief that spiritual views are private, and perception of physician
time pressure.27 Lack of time and capability frequently emerge as barriers to
physician enquiry.28,29
There are a number of scales which can be used to elicit patients’ spiritual
beliefs and concerns: HOPE (Sources of Hope Organised religion Personal
spirituality and practices, Effect on medical care and end-of-life issues),30 FICA
(Faith, Importance/influence, Community, Address/apply),31 SPIRIT (Spiritual
belief system, Personal spirituality, Integration with a spiritual community,
Ritualised practices and restrictions, Implications for medical care, Terminal
event planning). Acquaintance with these scales might facilitate communication
about spirituality and spiritual distress with patients.32
TABLE 5.1 The SPIRIT questionnaire
S Spiritual belief system

P Personal spirituality
I Integration with a spiritual community
R Ritualised practice and restrictions
I Implications for medical care
T Terminal event planning
DEALING WITH SPIRITUAL DISTRESS

General spiritual care involves recognising and responding to the diverse expres-
sions of spirituality encountered in patients and their families and involves
compassion, presence, listening and the encouragement of realistic hope. It
might not involve any discussion of God or religion. Communication of spir-
itual issues may be facilitated through the use of media apart from direct verbal
communication including poetry, myth and music. Although general spiritual
care may be provided by any health professional, specialised spiritual care often
involves understanding and helping with specific theological beliefs and conflicts
and may require the expertise of a chaplain.
All health professionals working in palliative care settings need to be aware
of how spiritual issues impact upon the course of illness in their patients. This
should include the ability to elicit a spiritual history, competency in commu-
nicating about spiritual issues and an awareness of when referral to a religious
professional is appropriate. Chaplains, with their unique focus upon religion
and spirituality can provide expert advice on spiritual care of patients. Through
their training in pastoral counselling and their knowledge of religious ritual
they may be able to address existential issues from a faith-based perspective
and provide meaning and hope. Furthermore, they may have a teaching role
for other health professionals.33 It is commonplace now for chaplains to be
part of the multidisciplinary team. The discussion of spirituality with patients
is emotionally demanding and mechanisms should be in place both in hos-
pices and in community palliative care teams to support professionals in this
endeavour. There is a need for structured educational programmes to facilitate
spiritual competency and future research should focus upon the assessment of
outcomes from such programmes both in terms of competencies and of patient
outcomes.
REFERENCES
1 Austin D, Jennings CJ. Grief and religious belief: does belief moderate depression?
Death Studies. 1993; 17: 487–96.
2 Peterson EA, Nelson K. How to meet your clients’ spiritual needs. J Psychosocial
Nursing. 1987; 25: 34–9.
3 Shafranske E, Malony HM. Clinical psychologists’ religious and spiritual orientations
and their practice of psychotherapy. Psychotherapy. 1990; 27: 72–8.
4 Geoffrey M. ‘Diagnosing’ and ‘managing’ spiritual distress in palliative care: creating an
intellectual framework for spirituality useable in clinical practice. Australasian Medical
Journal (Online). 2010; May 11.
5 True G, Phipps EJ, Braitman LE, et al. Treatment preferences and advance care planning
at end of life: the role of ethnicity and spiritual coping in cancer patients. Ann Behav
Med. 2005; 30: 174–9.
6 Grant E, Murray SA, Kendall M, et al. Spiritual issues and needs: perspectives from
patients with advanced cancer and nonmalignant disease – a qualitative study. Palliat
Support Care. 2004; 2: 371–8.
7 Holmes SM, Rabow MW, Dibble SL. Screening the soul: communication regarding
spiritual concerns among primary care physicians and seriously ill patients approach-
ing the end of life. Am J Hosp Palliat Care. 2006; 23: 25–33.
8 Moadel A, Morgan C, Fatone A, et al. Seeking meaning and hope: self-reported spir-
itual and existential needs among an ethnically-diverse cancer patient population.
Psychooncology. 1999; 8: 378–85.
9 Fehring RJ, Miller JF, Shaw C. Spiritual well-being, religiosity, hope, depression, and
other mood states in elderly people coping with cancer. Oncol Nurs Forum. 1997; 24:
663–71.
10 Nelson CJ, Rosenfeld B, Breitbart W, et al. Spirituality, religion, and depression in the
terminally ill. Psychosomatics. 2002; 43: 213–20.
11 Sulmasy DP. Spiritual issues in the care of the dying. JAMA. 2006; 296: 1385–92.
12 McClain CS, Rosenfeld B, Breitbart W. Effect of spiritual well-being on end-of-life
despair in terminally ill cancer patients. Lancet. 2003; 361: 1603–7.
13 Balboni TA, Paulk ME, Balboni MJ, et al. Provision of spiritual care to patients with
advanced cancer: associations with medical care and quality of life near death. J Clin
Oncol. 2010; 28: 445–52.
14 Chaturvedi S. Spiritual issues at end of life. Indian J Pall Care. 2007; 13: 48–52.
15 Tarakeshwar N, Vanderwerker LC, Paulk E, et al. Religious coping is associated with
the quality of life of patients with advanced cancer. J Palliat Med. 2006; 9: 646–57.
16 Clarke DM, Kissane DW. Demoralization: its phenomenology and importance. Aust
N Z J Psychiatry. 2002; 36: 733–42.
17 Mako C, Galek K, Poppito SR. Spiritual pain among patients with advanced cancer in
palliative care. J Palliat Med. 2006; 9: 1106–13.
18 Maugans TA, Wadland WC. Religion and family medicine: a survey of physicians and
patients. J Fam Pract. 1991; 32: 210–13.
19 King D, Bushwick B. Beliefs and attitudes of hospital inpatients about faith healing and
prayer. J Fam Pract. 1994; 39: 349–52.
20 Ehman J, Ott B, Short T, et al. Do patients want physicians to enquire about their
spiritual and religious beliefs if they become gravely ill? Arch Intern Med. 1999; 159:
1803–6.
21 MacLean CD, Susi B, Phifer N, et al. Patient preference for physician discussion and
practice of spirituality. J Gen Intern Med. 2003; 18: 38–43.
22 Ehman J, Ott BB, Short TH, et al. Do patients want physicians to inquire about their
spiritual or religious beliefs if they become gravely ill? Arch Intern Med.1999; 159:
1803–6.
23 McCord G, Gilchrist V, Grossman S, et al. Discussing spirituality with patients: a
rational and ethical approach. Ann Fam Med. 2004; 2: 356–61.
24 Ellis R, Campbell JD. Patients’ views about discussing spiritual issues with primary care
physicians. Southern Med J. 2004; 97: 1158–64.
25 Monroe MH, Bynum D, Susi B, et al. Primary care physician preferences regarding
spiritual behavior in medical practice. Arch Intern Med. 2003; 163: 2751–6.
26 Steinhauser KE, Voils CI, Clipp EC, et al. ‘Are you at peace?’: one item to probe spiritual
concerns at the end of life. Arch Intern Med. 2006; 166: 101–5.
27 Chibnall JT, Bennett ML, Videen SD, et al. Identifying barriers to psychosocial spiritual
care at the end of life: a physician group study. Am J Hosp Palliat Med. 2004; 21: 419–26.
28 Coyle N, Sculco L. Communication and the patient/physician relationship: a phenon-
menological inquiry. J Support Oncol. 2003; 1: 206–15.
29 Kristeller JL, Zumbrun CS, Schilling RF. ‘I would if I could’: how oncologists and
oncology nurses address spiritual distress in cancer patients. Psychooncology. 1999; 8:
451–8.
30 Anandrajah D, Hight E. Spirituality and medical practice: using the HOPE questions
as a practical tool for spirituality assessment. Am Fam Physician. 2001; 63: 81–9.
31 Puchalsky CM, Romer AL. Taking a spiritual history allows clinicians to understand
patients more fully. J Palliat Med. 2000; 3: 129–37.
32 Maugans TA. The SPIRITual history. Arch Fam Med. 1996; 5: 11–16.
33 Williams E. Holistic medical care – the role of chaplains in a multidisciplinary team.
Scottish J Health Care Chaplaincy. 2008; 11: 9–16.
CHAPTER 6
Pain and psychiatry
Pain is no evil unless it conquers us.
Charles Kingsley (1819–75)1
The management of pain is a basic tenet of palliative care practice. Some of the
most complex and perplexing aspects of pain are those factors considered ‘non-
organic’. Pain, psychiatry and psychology are intimately interconnected.
THE EXPERIENCE OF PAIN
Illness is the doctor to whom we pay most heed: to kindness, to knowledge

we make promises only: to pain we obey.
Marcel Proust (1871–1922)2
Pain is ‘an unpleasant sensory and emotional experience, associated with actual
or potential tissue damage, or described in terms of such damage’.3 Pain is what
the patient says hurts. This by now well-accepted view highlights that pain is an
experiential and emotional symptom. Pain is a ‘somatopsychic’ experience and
its intensity depends both on the extent of tissue damage and on the patient’s
psychological state. There exists a conflict between the noxious stimulus and
the whole individual. Pain, the expression of this conflict, is a viciously ‘real’
experience for the sufferer. Each individual perceives and portrays pain in an
idiosyncratic fashion. There is generally a poor correlation between tissue pathol-
ogy, disability and treatment response.4 Women are more sensitive to noxious
stimuli than men.5 Although the threshold for pain in the elderly is not raised,
tolerance to perceiving pain is, and they are often diffident asking for pain relief.6
These factors may partially account for the inadequate analgesic relief offered
to the elderly. Cultural, personality and situational influences may enhance
59
expressions of pain or inhibit the behavioural portrayal of pain. Insensitivity to

pain, a rare congenital condition, is a major disability, for individuals with this
disorder are deprived the protection of pain, yet ‘stress analgesia’, in dangerous
predicaments, may be life saving. The physiological clinical signs of pain tend
to fade with persistence of pain. Psychological factors are integrated into the
pain experience. Uncontrolled pain can mimic psychiatric disorders. It can also
aggravate and precipitate mental disorder. Conversely, affective, cognitive and
behavioural factors have significant influence upon pain.
Pain cannot be measured objectively. Visual analogue scales are the preferred,
easiest and best measures of pain. The magnitude of the numerical score has little
meaning except when measurements are made serially and comparisons made.
Each individual perceives pain uniquely, but over time reasonable consistency
and reliability in reporting can be achieved using these scales. Yet defining a
meaningful decrease on pain rating scales is difficult. ‘Moderate relief ’ or ‘much
improved’ corresponds to reductions on pain scales of about 30%.7 Pain rating
scales are influenced by many factors including contextual circumstances, dis-
ease state, mental status, personality, memory of prior painful states and worries
concerning the cause of the pain. The scores tend to be more reflective of the
affective and emotional aspects of the pain than of the sensory intensity created
by physiological pathology.8 The clinician adds to this conglomeration of influ-
ences with medical knowledge of the painful lesion, experience of how similar
pathology in other patients is portrayed and an impression of the situational
influences. The resultant clinical estimate of pain is, however, likely to be only
approximate.
Adequate pain relief is considered a human right by some advocates. Pain is
common, and treatment is generally effective and cheap. Treatment becoming a
‘right’ may encourage the good clinical and ethical practice that this symptom
demands and deserves. However, false and unrealistic promises of pain relief
may be hurtful to the patient and unethical practice on the part of the doctor.9
Honest forewarning of the expectation of analgesia success is best practice.
PAIN AND TERMINAL ILLNESS

Pain is a common problem for cancer patients. In advanced disease, 70–90%
experience pain, and among those undergoing active treatment at earlier stages
for a solid tumour, the prevalence is 30–50%.10 It was claimed in the 1990s that
adequate relief of pain should be achievable with simple drug regimes in as
many as 90%.10 However, the management of cancer pain is yet to be perfected,
indeed it appears to be becoming more challenging. With the shift of cancer
from an acute to a chronic condition, pains can become persistent. Together
with the accumulation of multi-organ complications (involving the nervous
system), neuropathic pain is more likely and the neurotoxic adverse effects of
PAIN AND PSYCHIATRY 61
opioids, such as hyperalgesia, are more pronounced.11 Undoubtedly, considerably

improved pain management has been practised in many settings (particularly
palliative care) over recent decades. Yet pain still remains underrecognised and
undertreated in terminal illness.
Acute pain serves to warn the individual of bodily harm and is considered
the ‘fifth vital sign’. It invites affective, cognitive and behavioural responses
designed to result in the relief of the symptom and prevent further tissue dam-
age. Chronic pain has little if any adaptive biological function, and generally is
contrary to good-quality functioning. Acute and chronic pains are very different
clinical entities. In palliative care, most pains are nocioceptive (or somatic) and
‘acute’ in the sense that they signal physical damage being caused by the disease.
Nocioceptive pain is the cause of as much as three-quarters of cancer pain.10
Incident pain, pain on movement, can be particularly disabling and erosive to
quality of life. Damage to the nervous system by disease or injury may result in
neuropathic pain, which is typically described by the patient as being ‘burning,
shooting and/or stabbing’. Neuropathic pain is often seen in the later phase of
many diseases of the peripheral or central nervous system, including malignant
disease, AIDS, multiple sclerosis and Parkinson’s disease. Such pains tend to
endure, even if the original causative factor is removed, and they are difficult to
relieve. Neuropathic pains are often centrally represented in the nervous system.
The pathophysiological mechanisms of neuropathic pain are multiple, each of
which may respond differently to medications, with different mechanisms of
action. Partial responses are usually achieved, and polypharmacy is the norm.
Response rates with opioids alone are about 50%.12 The clinical belief that neu-
ropathic pain does not respond to opioids has been disproven.13 Though less
responsive, it is partially responsive to opioids. In acute neuropathic cancer
pain opioid analgesics and tramadol may be first-line treatment.14 Subsequently
(and usually in addition), a secondary-amine TCA (nortriptyline) or an SSNRI
(duloxetine, venlafaxine) may be considered, followed by gabapentin or prega-
balin, anticonvulsants (valproate) and topical agents (lignocaine, capsaicin).14
‘Complete’ relief of neuropathic pain with multiple agents may be achievable in
50–60% of research trial patients.15 In clinical practice, relief of such pain is pos-
sible in perhaps only 20–30%. The management needs to be individualised, for
the responses are unpredictable.14 In cancer care invariably the less responsive
patients are those suffering neuropathic pains. Visceral pain, caused by neoplas-
tic involvement of internal organs and their nerve supply, may be referred to an
anatomical site distinct from the lesion. These pains are difficult for the patient
to describe, and are often associated with strong emotional and autonomic
responses. Psychosocial factors influence visceral pain, which is probably a
variant of (autonomic) neuropathic pain. Psychic or emotional pain is the most
perplexing of pains to articulate, conceptualise and manage. Treatment-related
pain syndromes are usually neuropathic. Refractory pains are most often inci-
dent and neuropathic.
Uncontrolled or poorly controlled pain, in addition to the discomfort felt, may
aggravate and/or precipitate psychological and psychiatric symptoms. Similar
neurotransmitter changes to those of depression are induced.16 The neurobiology
of pain and depression overlap. Misery and desperation ensue. Pain dominates
existence and provokes pleading care-eliciting behaviours. Control of pain needs
to be of the highest treatment priority in palliative medicine. Not until pain
is manageable can the assessment of other symptoms proceed. Clinically, it is
important to appreciate that the most severe pain is the pain of most immediate
concern to the patient. In those with multiple sites of pain, the relief of the most
severe pain may highlight other pains, previously quiescent. Pain is rarely static.
Pain assessment needs to be continually repeated together with ongoing review
and titration of analgesia.
THE PSYCHOLOGY OF PAIN
[Pain is] outside the senses and within the passions of the soul.
Aristotle (384–322 BC)17
Pain elicits alarm, anxiety and fear. Anxiety amplifies the pain experience.
Anxiety is an internal process, whereas fear is a response to an external threat-
ening stimulus. Patient identification of initiating or aggravating influences on
their pain results in protective avoidance behaviours. These include presenting
for medical assistance, if the patient has knowledge that the doctor may have
effective therapies, and avoiding any activity that may provoke further pain.
Expecting and anticipating pain reinforces this behaviour. Patients with greater
pain-related anxiety tend to overpredict new pain.18 ‘Hurt does not equal harm’,
quipped the pioneering pain psychologist, Fordyce.19 Progressive demobilisation
and deactivation result. ‘Use it or lose it’.19 Fear of moving the neck leads to dis-
abilities such as muscular reactivity, deconditioning and guarded movement of
the neck (kinesiophobia). Thus a vicious and ultimately counterproductive cycle
is established. Not only is the conditioned stimulus avoided (thus this behav-
iour cannot be extinguished), but sympathetic nervous system arousal further
lowers nocioceptive thresholds. Hypervigilant and physiologically stressed, the
individual struggles to maintain control. Anxiety seldom occurs in isolation,
and depression is highly likely to further contaminate this response. While this
phenomenon is particularly well described in chronic non-malignant pain, it is
also a typical response to chronic cancer pain. Pain entices a cognitive response.
Pain has meaning. Increased levels of pain may be believed by the patient to be
caused by spread or recurrence of cancer. This belief has been shown to result in
more intense pain than when the pain is believed to be caused by other factors.20
Catastrophic thinking, the amplification of threatening information, intensifies
distress, pain and self-perceived disability. Negative thoughts about personal
or social competency increase pain intensity and emotional distress.21 ‘Mental
defeat’ is a psychological construct applied to these psychological disabilities.22
Pain challenges personal coping and can easily unsettle psychological equilib-
rium. Information and reassurances result in inconsistent, sometimes small,
sometimes transient, and sometimes paradoxical effects on pain.23 Behavioural,
cognitive and emotional therapeutic strategies are required.
In response to an unpleasant stimulus, ‘manipulative’ behaviours are evoked
in an attempt to ward off the unwelcome sensory experience. Anger may erupt.
This response is reported in 70% of chronic pain patients, and is directed at the
self in 74%, and healthcare professionals in 62%.24 Anger is not necessarily hostile
and goal-directed aggression. It may be verbally expressive and explorative of
options as to how the pain may be relieved. It can direct appropriate and cultur-
ally acceptable strategies of eliciting the required healthcare. Men are more liable
to hostile anger, women tend to be more articulate and expressive.24 Direct and
determined help-seeking communication and behaviour should be supported.
The manipulation can be creative. When such responses have failed to provide
relief, and pain persists (for medicine is unable to oblige), the ‘manipulation’ can
become interpreted as ‘manipulative’ (in the pejorative meaning of the word).
Concepts of psychologically induced pain have a long history. Freud’s case
report of Fraulein Elisabeth R in 1892 has been cited as the first ‘scientific’
report of conversion or psychogenic pain.25 Freud actually presented the case
to illustrate that psychological conflicts could aggravate and maintain the pain
of ‘rheumatism’. Beecher’s brilliant study on wounded World War II soldiers
requiring little analgesia, until after the battle, demonstrated ‘stress analgesia’.26
‘If you have something better to do, you do not hurt’.19 Arousal and distraction
can mute pain transiently, but this doesn’t make the pain psychogenic. The con-
cept of ‘pain-prone’ patients in whom psychic factors played a primary role in
the genesis of pain,27 encouraged DSM-III (in 1980) to introduce the category
‘psychogenic pain’, which was renamed ‘somatoform pain disorder’ in subsequent
versions. Pain is, however, rarely generated and maintained by psychological
forces alone.28 A more reasonable conceptualisation of psychogenic pain is that
of psychologically amplified pain of somatic origin. Pain has an organic initiator
and psychosocial influencing factors. Saunders introduced to palliative care the
term ‘total pain’, to refer to the multiplicity of psychological, social, bureaucratic,
financial and spiritual factors contributing to, and perhaps creating, pain in the
cancer patient.29 Despite ‘adequate analgesia’, the pain perseveres unaltered. This
is a useful clinical concept provided the organicity of the pain is not entirely
dismissed. A clinician’s response to therapeutic failure can be that of therapeutic

nihilism, and the propensity is to project blame onto the patient for the failure of
a usually effective intervention. ‘Total pain’ could represent inadequate clinical
and technical expertise, or it can describe a syndrome in which the perpetuating
and maintaining influences on a fundamentally ‘organic’ pain are psychosocial.
THE PSYCHIATRY OF PAIN

Acute pain is critical to the survival of an organism, generating reflex withdrawal
and avoidance behaviours. Persisting pain may result in central sensitisation,
a sort of pathological plasticity of the CNS.30 After repeated or intensively
noxious stimuli the threshold for the activation of the pain system falls. A
homeostatic resetting of the analgesic systems occurs. The reactivity of the CNS
becomes enhanced. Even in the absence of ongoing tissue damage, the state of
heightened sensitivity persists awhile and then returns over time to the normal
baseline, except in those destined to experience chronic pain. Previously benign
stimuli provoke an enhanced (allodynia) or exaggerated (hyperalgesia) pain
experience. This is particularly prone to occur with neuropathic pain. Chronic
non-malignant pain is a central and not peripheral nervous system disorder, thus
is intimately connected with the emotions.31 The mesocorticolimbic dopamin-
ergic and endogenous opioid circuits, which are involved in reward/salience/
motivational mechanisms, muddy the differentiations between physiological and
noxious stimuli, both internally and externally. Unrelieved nocioceptive pains
such as untreated cancer pain, probably acquire central sensitisation in addition
to the peripheral hurt.
The anxiety and fear induced by acute pain, if the pain continues, is com-
pounded by affective distress, and eventually perhaps affective disorder. A
high percentage of those with persisting non-malignant pain become clinically
depressed. Conversely, depressive disorder may present with pain, the so-called
‘masked depression’. In an international study, 69% of patients with depression
presented with only somatic symptoms, of which pain complaints were com-
monest.32 At least 50% of those clinically depressed complain of bodily pains.32
After insomnia, pain is the commonest symptom of depression. Cultural fac-
tors do influence the symptoms of depressive illness, and pain symptoms in
depressed non-Western patients are more frequently clinically encountered. The
causal relationship between pain and depression has long been controversial.
‘Pain-prone’ personalities in whom a depressive scar is reactivated by pain, or
whose personal mastery falters under the impact of pain are such propositions.
The ‘consequence’ model is the most compelling, and particularly in cancer
patients in whom there may be no prior history of depression. The cause or
effect arguments, to the pragmatic clinician are rarely relevant for they don’t
usually dictate management. The intimate relationship between mood and pain
is undoubted and their mutual aggravating influence on each other likewise.

Pain can cause depression, and depression can enhance pain. The neurobio-
logical explanation of this association may be that the descending pathways of
pain modulation in the spinal cord utilise monoamine neurotransmitters. A
decrease of serotonin and/or noradrenaline in these pathways would relax the
central inhibitory control and release the full intensity of the noxious stimulus.
Internal stimuli concerning routine bodily functions, such as digestion and heart
rate, are normally suppressed from consciousness by descending serotonergic
and noradrenergic pathways. This suppression is not constant, rather it acts as
a homeostatic regulator by determining whether attention should be directed
towards external threats or to sensations coming from within the body. These
regulators account for stress analgesia. If the catecholamines are depleted,
routine internal sensory input may become disagreeable (and painful), hence
the mechanism of the amplification of pain in depression. In addition to the
neurophysiological theory, it is important to consider cognitive and behavioural
symptoms of depression compounding the situation. A loss of control is initiated
by pain; emerging helplessness as relief is not acquired, catastrophic thinking,
avoidance behaviours, and brooding hopelessness leading to non-compliance
and suicidal thoughts, all add to the desperation. Uncontrolled pain is a major
factor in suicidal ideation.33 Severe unrelieved pain erodes the sense of control,
and may entice desperate behaviours, including suicide attempts.
Sleep disturbance secondary to the discomfort of pain and the coexistent
depressive disorder further undermines the ability to cope. Reduced sleep quan-
tity and quality correlate with pain, depression and negative affectivity.34 Sleep
is interrupted by pain, and tiredness sabotages coping strategies. Poor sleep is
a contributing factor in lowering the pain threshold.35 Sleep rebound consecu-
tive to sleep deprivation produces an analgesic effect similar to paracetamol or
non-steroidal anti-inflammatory drugs (NSAIDs) in volunteers.35 Not only
does insomnia aggravate pain, it may encourage hypnotic and analgesic mis-
use. Paracetamol is not uncommonly used by the lay public as a mild hypnotic.
NSAID use may disrupt sleep by interfering with melatonin levels and body tem-
perature. These theoretical consequences, however, are likely to be overwhelmed
by the analgesic-induced improvement of sleep. Opioids have been traditionally
used as hypnotics, mainly due to their (transient) action on kappa receptors.
However, opioids and the sedative side effects of tricyclic antidepressants (TCAs)
and anticonvulsants may exacerbate pre-existing obstructive sleep apnoea. Sleep
disturbance should be a major therapeutic target in pain management.
A lack of pain sensitisation, or hypoalgesia, has been noted in schizophre-
nia. Occasionally, these persons seem untroubled by the pain of acute disease
or injury.36 Borderline personality disordered persons’ ability to endure, in
crises, self-mutilatory injuries may be accounted for by enhanced opioid
neurotransmission (shown on PET and fMRI scanning) and increased pain

thresholds.31 The symptoms of acute PTSD may be eased by opioids, but if the
disorder becomes chronic an increased central opiodergic tone evolves (hence
the possibility of the therapeutic use of opioid antagonists).31 Pain, paired with
the recollections of the emotional trauma, can become a conditioned stimulus
creating a ‘mutual maintenance’ cycle in PTSD.31 Traumatic distress aggravates
pain and vice versa. The increasing medicinal use of maintenance opioids for
chronic non-malignant pain over the last two decades, and the rising tide of
fatal overdoses of opioids over this period,37 illustrates the close, and tortuous,
relationship between pain and addiction. Acute pain and euphorogenic drugs
activate dopamine transmission in the brain reward circuitry, whereas persist-
ing pain and analgesic medications produce the opposite effect, accompanied by
reduced motivation toward normally pleasurable stimuli. Pain and drugs dys-
regulate the mesolimbic dopaminergic circuits, increasing the incentive salience
assigned to pain or drug-related cues. Additionally, the repeated experiences may
lead to the overlearning of the motivational significance of pain or drug cues.
Pseudo-addiction and addiction may result. Theoretically, both undertreated and
overtreated pain may lead to drug misuse and abuse. This is a consequence of the
pain system being embedded within the extensive emotion/reward/motivation
circuits of the brain.31
PSYCHIATRIC ISSUES IN THE MANAGEMENT OF PAIN

Psychotherapy of pain
Teasing out cause and effect of a particular psychological variable is clinically nei-
ther easy nor rewarding. Pain management needs to incorporate psychological
interventions aimed at effect rather than cause. Pragmatic and ‘here-and-now’
interventions are necessary, rather than analysis of the cause. Explanation,
reassurance, cognitive reframing of negative ideation, and refreshing coping
strategies using relaxation, hypnosis, mindfulness meditation, and distraction
can be of benefit. Reinforcing coping and cognitive reappraisal augments analge-
sic pharmacotherapies. Analgesic medications are the foundation of cancer pain
management. A pill can be of benefit, but a pill and supportive words can be of
greater benefit. The nurse is a powerful analgesic. The destructive psychological
spiral initiated by a painful stimulus can be checked by short and simple psycho-
therapy, enhancing the prospects of a better response to medication.
Pharmacotherapy of pain
Opioid analgesics
The analgesic effects of opioids (chemicals with activity similar to opium)
typically decrease the distressing affective component of pain rather than the
sensation. The pain remains, though many patients acknowledge that following
taking opioids they are less bothered by the unpleasant sensation. Opioids have
a pivotal role in managing cancer pain. The ‘gold-standard’, ‘strong’ opioid is
morphine, an analgesic that provides effective relief in about 75% of cancer pain
patients. Opioids are the most effective analgesic for acute pain but in chronic
pain their effectiveness falls to perhaps 30–40%. Nocioceptive pain is the most
opioid-responsive of pains. For neuropathic and visceral pain, opioids are par-
tially effective. High-dosage morphine, at oral doses greater than 300–400 mg/24
hours, is suggestive of non-responsiveness, and consideration of adding a co-
analgesic or switching to an alternate opioid is required. Despite limited evidence
of efficacy in chronic pain, there has been since the 1990s an explosive increase of
opioid prescribing for non-malignant pain.38 These have been introduced early,
often prior to adequate multidisciplinary pain clinic assessment. This practice is
increasingly raising clinical concerns because of ineffectiveness and drug misuse.
In cancer care the management of breakthrough pain (incident, spontaneous)
is hampered by the lack of very rapid onset opioids, hence the recent interest in
intranasal, buccal, and sublingual delivery methods and formulations.
HISTORY
Opium, the sap of Papaver somniferum, a poppy native to the lakes of
Switzerland,39 colonised to the preferable climatic conditions of the Near East
over 5000 years ago. The term ‘opiate’ refers to derivatives of the opium poppy.
‘Narcotic’ is a legal and not a medical term. Opium was a common component of
many cough, cold, diarrhoea and teething mixtures until the twentieth century.
The drug was used liberally, often as laudanum (an alcohol and opium solution).
Sertürner, in 1806, identified the active ingredient of opium: morphine. It was
the invention of the hypodermic needle by Wood in 1853 that made possible the
administration of very potent, and dependence-inducing, morphine. ‘Soldier’s
disease’, morphine dependency, was common during the American Civil War.
It was during the Victorian era that morphine-induced ‘euthanasia’ became the
preferred mode of medical death. The trafficking of opium from India to China
by the British had, by the mid-nineteenth century, created estimates of up to 25%
of the Chinese population dependent on the drug, though these high figures are
disputed by more recent scholars.40 From a position of social acceptance, opium
came to be propagated as the ‘evil drug’ of addiction. In Shanghai, in 1909, the
first international meeting on matters of drug control was convened in response
to this rising moral panic. This initiated the dramatic change towards tight and
restrictive regulations. Not only did public attitudes alter, doctors developed
‘opiophobia’, a fear of prescribing opioids. Cancer patients suffered unnecessarily.
It wasn’t until the emerging hospice movement in the 1950s that the usefulness
and safety of morphine for the dying was re-emphasised. The development of
sustained-release formulations in the 1980s again refined clinical use. In 1986
the World Health Organization (WHO) analgesic ‘ladder’ was published.41

Medicinal availability of morphine remains severely limited in many countries
because of the mythology of its abuse, morphine’s association with organised
crime, and cost. Methadone and other opioids are alternatives in some of these
countries, but many cancer victims worldwide still die in pain.
ADVERSE EFFECTS OF OPIOIDS

All drugs have adverse effects, and opioids are no exception. The opioid recep-
tors in the brain, spinal cord and peripheral nervous system have differing
functions. Mu receptors are most important for analgesia but also induce res-
piratory depression, miosis, gut motility and euphoria. The kappa and delta
receptors have some roles in analgesia, but kappa-receptor stimulation leads
to psychiatric adverse drug reactions (ADRs). There are many other opioid
receptors of as yet uncertain functions. Each individual person has differ-
ing and unique opioid-receptor profiles and genetic expression of enzymes
responsible for the metabolism of opioids. Single-nucleotide polymorphisms
(SNP) in the gene encoding the mu receptor have been linked to the variability
of responses to opioids.42 Pharmacogenetics may ultimately allow for accurate
individualised dosing of the opioid. Opioids to varying degrees antagonise
N-methyl-D-aspartate (NMDA) receptors and activate the descending serotonin
and noradrenaline pathways from the brainstem. There is considerable indi-
vidual variability regarding the effects and adverse effects of these medications.
Renal failure is a particular risk factor for morphine side effects, as its very active
metabolite morphine-6-glucuronide (M6G) is renally excreted. If used over large
wounds, topical opioids may even induce systemic effects. The introduction of
an alternative and effective analgesic, such as a nerve block or surgery, can cause
opioid toxicity if the opioid dose is not appropriately adjusted. Chronic opioid
use may result in hypogonadism and immunological compromise, at least in
animal models.
Opioid neuropsychiatric adverse reactions include (see Table 6.1):
➤ Lowering of the level of consciousness (sedation, sleep disruption, delirium):
opioids commonly cause sedation on initiation and during dose escalation,
but tolerance to this usually develops within days. The widespread
public belief that ‘morphine kills the dying’ is related to its narcosing
effects. Differing opioids have differing sedating and anticholinergic
effects, thus opioid rotation may be an option, as might the addition of a
psychostimulant or more gradual dose increments. Opioids suppress rapid
eye movement (REM) sleep and to a lesser extent non-REM (NREM)
sleep, thus total sleep time and sleep efficiency are reduced.43 Aggravation
of central sleep apnoea may occur. Opioids disrupt sleep architecture
and a more fragmented sleep may result, although it is often difficult to
establish whether this is attributable to the drug or the underlying disease.43

Methylphenidate has been shown to improve this sleep disruption.44
In clinical practice the sedation and analgesia associated with opioids
tends to enhance rather than disrupt sleep. Despite these effects on sleep,
morphine is not named after Morpheus, the god of sleep, but rather named
because of its propensity to distort shapes (fr. Gk. morphe–; form, shape).
The incidence of morphine-induced confusion is a few per cent, though
recent authors suggest a much higher rate of opioid-induced hypoactive
deliria.45 Opioids are reported to precipitate delirium and cause it.44–46
Clinically differentiating the precise causes of delirium towards the end of
life is not usually possible. Opioids do affect the cholinergic–dopaminergic
balance. That this may be commoner with morphine than other opioids
may be accounted for by the accumulation of M6G, particularly as renal
function falters. The delirogenic potential of opioids may be reduced
by opioid rotation or substitution,47 the introduction of haloperidol,
discontinuation of other anticholinergic medications, the introduction of
procholinergic medication, or hydration (to increase morphine metabolite
clearance). Improvements are recorded in 60–70% with opioid rotation and
hydration.45 Most authors suggest dose reductions of 50–75% on opioid
substitution. The reduced dose may be as relevant as the change of opioid.
➤ Cognitive impairments: the prevalence of cognitive dysfunction in the
terminally ill is very high, particularly as death approaches. Separating
disease from drug effects is difficult. In healthy volunteers, parenteral
opioids have been associated with significant dose-related cognitive
impairments, whereas oral opioids are associated with only insignificant or
mild deficits, and even improved cognition.46 Current evidence of harm,
benefit or lack of appreciable effect of a long-term stable opioid regime on
cognitive functioning is still limited.48 In patients with advanced cancer,
little or no deterioration of cognitive performance has been demonstrated
when initiated on opioids.46 Pain is associated with poorer performance
on memory testing than treatment with opioids.45 The rate of processing
information, rather than accuracy, is the prominent cognitive impairment
with opioids. This is less than with lorazepam.45 Impairments are greatest
with pethidine, less with hydromorphine, less again with morphine,
and less again with methadone.45 The impairments are dose related,45
and tolerance develops to them within days. In patients with chronic
non-malignant pain studies indicate mainly improved cognitions on
opioids,46 except for those on tricyclic antidepressants (TCAs).49 Many
patients on opioids report mental dulling, fuzziness, being more accident
prone, making more mistakes and struggling with cognitive dexterity.
The consensus is that on stable oral doses, transient and mild cognitive
impairments may occur. Management by dose reduction, opioid rotation,

hydration, and with psychostimulants has been proposed. The most
effective intervention may be adequate pain relief.46
➤ Perceptual impairments: while there are numerous anecdotal reports
of opioid-induced hallucinations and nightmares, particularly in
postoperative settings, disentangling these clinical phenomena from
prodromal symptoms of delirium is most difficult. In a study of hospice
patients, almost half experienced visual hallucinations, this being more
likely in those taking morphine, although this association was not strong.50
Morphine may be ‘blamed’ for such mental aberrations but certainly it can
cause visual distortions.
➤ Psychomotor impairments: the evidence for an adverse effect of opioids
on psychomotor abilities, such as driving, is conflicting. There is no
compelling medical evidence that driving is unsafe while taking opioids,
provided the dose is stable.46,51 Long-term use of morphine had only a slight
effect on driving.51 A simple bedside test of opioid-induced psychomotor
impairment is to ask the patient to tap their finger for 10 seconds. Most
only manage three taps.
➤ Mood alteration: the seventeenth-century English doctor Napier prescribed
opiates for 8% of his melancholic patients (and more commonly for his
psychotic patients).52 In 1850, opioids were considered to be specific
treatments for melancholia.53 The ‘laudanum cure’, especially recommended
for agitated depression, consisting of 16 mg tincture of opiate, increased by
3mg/day for 22 days and then gradually reduced by 2 mg/day, was used up
to the mid-1950s.54 Positive mood effects have been demonstrated in cancer
patients treated with opioids.55 Low-dose buprenorphine has been used to
effectively treat refractory depression in seven patients.53 Long-term use
of codeine is associated with, but not proven to be causative of, depressive
symptoms.56 In persons with bipolar disorder, hydrocodone
was shown to precipitate a hypomanic/manic episode in about a third of
cases and had a mood-elevating effect in others who were depressed.57
Codeine as an antidepressant has not been shown to be effective.54
Nalorphine is an inducer of dysphoria because of its kappa-receptor
activity.58
➤ Tolerance: apoptosis and damage of neural cells by opioids is a major
cause of their adverse effects.12,59 There may be direct damage to the
receptors,59 or the effect may be because of activation of NMDA receptors.60
Myoclonus, noted often at high opioid doses, especially in the presence of
pre-existing spinal lesions, may be a sign of neurotransmitter aberrations
induced by the opioid. Tolerance to opioids (where the same dose results
in less analgesia or an increase dose fails to improve analgesia) in palliative
care patients occurs, but is rarely a clinical problem unless the doses are
high.12 Separating tolerance and disease progression clinically is most
challenging. Tolerance may be to both analgesia and to opioid adverse
effects. Stable dosing regimes suggest it is not a frequent problem, but it
has been shown with parenteral opioids.61 Tolerance to sedation, cognitive
impairments, nausea and respiratory depression are well recognised.62
Acquired pharmacodynamic tolerance to opioids, that is from changes
in disposition or metabolism of the drug on repeat dosing, has been
demonstrated in animals,63 and involves changes to opioid and NMDA
receptors. Neuronal excitotoxicity is induced, thus increasing doses are
needed to achieve the same clinical effect. NMDA receptor antagonists
such as ketamine may prevent and reverse tolerance, and thereby
hyperalgesia. Alternative opioids, particularly methadone, may have
inherent NMDA antagonism, thus rotation is a reasonable therapeutic
option. Tolerance to methadone has been described.64 It has also been
demonstrated that individuals receiving methadone maintenance (for drug
abuse) have lower pain thresholds than controls,65 though this may be a
reflection of non-pharmacological influences.
➤ Hyperalgesia: opioid-induced hyperalgesia (OIH), the enhanced response
to a stimulus that is normally painful, is emerging as a major problem
in the management of more chronic cancer (and non-malignant) pain.
Allodynia, pain induced by a stimulus that is not normally painful,
often occurs in conjunction with hyperalgesia. Though still a contestable
clinical reality,66 such paradoxical pains are well recognised in headache
and perioperative patients. In painful states central sensitisation can
produce pain hypersensitivity by changing the sensory response elicited
by normal inputs.30 This nociceptive sensitisation is a cruel consequence
of neural plasticity. The pain worsens despite increasing doses of opioids.
Hyperalgesia, ‘wind up’, is contributed to by the loss of GABAminergic
cells within the dorsal spinal cord,60 and alterations in NMDA and glycine
functions.59 Alternatively, opioids by their binding to microglia, causing
a release of neuroexcitatory pro-inflammatory cytokines, may be an
explanation for hyperalgesia,67 as may the activation of intracellular protein
kinase C causing ‘hyperalgesic priming’. The endogenous opioid system has
been shown not to be involved,68 but as yet the theoretical understanding
of this clinical conundrum is lacking. Switching opioids and/or NMDA
antagonism with ketamine may reverse hyperalgesia. Hyperkatifeia, a
volatile and negative emotion state, is also clinically observed in some
on maintenance opioid regimes.69 This may be the psyche’s equivalent of
hyperalgesia.
➤ Dependency: physical dependency is a state of adaptation that is
manifested by a withdrawal syndrome on abrupt cessation and rapid

dose reduction. It is not addiction and is an expected consequence to the
administration of certain medications including opioids, benzodiazepines
and corticosteroids. For most persons a few weeks of regular opioid use
creates physical dependency. It is less likely, and probably does not occur, if
the administered drug resolves a particular symptom (pain, anxiety) than
if the drug is used for recreational purposes. ‘Pseudo-addiction’ refers to
the seeking of additional medication secondary to undertreatment of pain.
Clinically, this may be encountered when managing pain in terminally
ill substance-misusing patients – in addition to the opioid maintenance
dose, these patients require an adequate analgesic dose (see Box 6.1).
Careful monitoring, urine testing and very firm rules prohibiting abuses
(intentional misuse) of prescription and supply are necessary for these
patients (see Chapter 14).
➤ Opioid withdrawal syndrome: in palliative care practice, withdrawal may
occur when switching from morphine to fentanyl, awaiting its onset of
action, or if the opioid rotation dose is grossly underestimated. Only
25% of the opioid dose is required to prevent withdrawal symptoms. The
autonomic discomfort and agitation of opioid withdrawal is unpleasant,
self-limiting and not medically dangerous unless otherwise the patient is
physically unwell.
➤ Addiction: the fear of addiction from the archetypal ‘dangerous drug’,
morphine, is common in the general community. Addiction refers to a
psychological dependence on a drug, compulsive use, continued use in
spite of harm, craving for the drug and loss of control over usage. There
is little evidence of addiction initiated by medicinal use, particularly
in cancer patients. Of nearly 12 000 patients given opioids only four
developed post-hospitalisation addiction, a rate of 0.03%.70 Of 10 000
burns patients prescribed opioids, 22 became addicted and all these
individuals had a past history of drug abuse.71 More recent prevalence
studies in cancer patients indicate up to 7.7% may become addicted,72
though this figure is only marginally greater than the lifetime prevalence
of substance abuse or dependence in the general population.73 However,
all these studies are fraught with methodological problems. In patients
with chronic pain conditions prescribed maintenance opioids, the risk of
iatrogenic addiction is low, less than a few per cent, though the studies
are hard to interpret.74 With the increased use of opioids in chronic non-
malignant pain this risk may be considerably greater.72 These risks may
be related to the characteristics of chronic pain, the duration of opioid
administration, the association with anxiety, affective, substance use and
personality compounders, the use of shorter-acting opioids, inadequate
dosing regimes, opioid-induced hyperalgesia, modest analgesic efficacy, the

financial attraction of diversion, and lax prescribing.75 There is no doubt
prior substance abuse increases the risk of addiction and some chronic pain
patients have such past histories. The drug is not, however, the sole factor
in drug addiction. There is an estimated community prevalence of chronic
pain of 20%. Early reports of the safety and efficacy of maintenance opioids
for these patients encouraged a more liberal approach to prescribing. It
is, however, emerging that the use of opioids in treating persistent pain
may risk addiction. Their use remains controversial for this indication,75
and tighter prescribing guidelines are being appropriately introduced. The
relevance for palliative medicine is that cancer patients may now survive
long enough to experience chronic pain.
TABLE 6.1 Neuropsychiatric adverse reactions of opioids
Clinical phenomena Symptoms

Lowering level of consciousness Sedation
Sleep disruption
Delirium
Cognitive impairment Slowing of rate of processing
Perceptual impairment Hallucinations
Psychomotor impairment Slowing of motor response
Myoclonus
Mood alteration Antidepressant action
CNS toxicity Tolerance
Hyperalgesia
Dependency
Withdrawal syndrome
Addiction
Opioids other than morphine

CODEINE
Initially isolated from opium in 1832, codeine’s active component is predomi-
nantly morphine. Codeine is a prodrug; the breakdown to morphine by the
cytochrome P450 enzyme 2D6 cannot occur in about 10% of the population
(those who lack this enzyme). Others possess an ultrafast metabolising vari-
ant of CYP2D6. These pathways are blocked by SSRIs (except citalopram). The
pharmacokinetics of codeine is unpredictable. Deaths have occurred in children
under conventional doses because of the genetic variability in metabolism.76
Very widely used in mild to moderate pain, and often available over the counter,
BOX 6.1 Terminology of drug behaviours
● Misuse: incorrect or improper use.

● Abuse: intentional misuse.
● Tolerance: the same dose resulting in a lesser effect.
● Dependency: physiological adaptation and withdrawal symptoms on
cessation.
● Pseudo-addiction: seeking of additional medication due to undertreatment
of pain
● Addiction: psychological dependency, compulsive use, craving, continued
use in spite of harm, loss of control over usage.
codeine’s use as an analgesic and anti-diarrhoea agent is limited, especially in

palliative medicine.
FENTANYL
A synthetic pure mu-opioid agonist developed initially in the 1950s, fentanyl
is 70–80 times more potent than morphine. Originally used as an anaesthetic
agent, a transdermal slow-release preparation was produced in the 1970s. The
advantages are of a predictable release of analgesia over 72 hours. However,
some patients psychologically appreciate the attention and interest shown in
the process of administering medications on a more frequent basis. Fentanyl
possesses less neurotoxicity than morphine. In some countries an oral transmu-
cosal formulation is available. ‘Lacing’ or dangerously augmenting illicit opioids
with fentanyl has been reported. Nasal spray delivery of injectable fentanyl or
sufentanyl is an alternative method of providing prompt relief for incident pain.
OXYCODONE
A semi-synthetic opioid which targets the kappa as well as the mu receptors,
oxycodone has been in clinical use since 1917. Derived from thebaine, it is twice
as potent as morphine. Fewer hallucinations than with morphine have been
reported.77 The rapid-acting oxycodone has proved very popular as a street drug
of abuse. The combination of oxycodone with an oral opioid antagonist causes
less constipation and it may also find a role in managing opioid addiction.
HYDROMORPHONE
An analogue of morphine, hydromorphone was first synthesised in 1921. It
is 7.5 times more potent and perhaps has less neurotoxic adverse effects than
morphine.
PETHIDINE
Pethidine, first synthesised in 1939, should no longer be used in medicine. It has
been shown to be devoid of analgesic effect (particularly the oral formulation). It
provides relief because of its strong psychotomimetic (exhilaration and sedation)
action.78 Its action on the sphincter of Oddi is no less than that of other opioids.
The major metabolite of pethidine, norpethidine, accumulates and is neurotoxic.
Myoclonus, agitation and seizures may occur. Ongoing use of parenteral pethi-
dine is highly addictive and not recommended.
BUPRENORPHINE
A semi-synthetic partial mu agonist, with delta and kappa activity, buprenor-
phine is safer in overdosage. Recently available as a transdermal preparation, it
is establishing a role in geriatric and palliative care. Naloxone may be combined
with buprenorphine to enhance its safety in a drug-abusing population.
METHADONE
Primarily a mu agonist, methadone also has NMDA antagonist activity and
inhibits the reuptake of serotonin and noradrenaline in the spinal cord. First
produced during World War II in Germany, it wasn’t until post-war that the
clinical usefulness of this compound was fully appreciated. Methadone is today
stigmatised because of its use in substance abuse clinics. It is as effective an anal-
gesic as morphine. Preferably it should be prescribed as split dosing for pain (in
contrast to drug abuse). The advantages of methadone are that it is effective and
cheap, however because of its long and individually variable half-life (15–120
hours), toxicity is a significant risk, especially in the elderly. Conversion doses
from morphine are difficult to estimate. It has (unproven) efficacy in neuro-
pathic pain. It is less sedating than morphine and has less appeal for illicit users.
Methadone is safe to use in renal compromised persons.
DIAMORPHINE (HEROIN)
Diamorphine is an opioid with 6–7 times the potency of morphine. No sub-
stantial therapeutic differences to morphine have been demonstrated, in spite
of clinicians’ impressions that it is more effective.
NALOXONE
An essential opioid antagonist in palliative care settings, naloxone also possesses,
at very low dosage, analgesic augmentation properties when combined with
morphine. Indeed if given in the absence of other opioids, naloxone has mild
analgesic action. The potentiation of the antinociceptive action of mu agonists
with ultra-low dose antagonists is an exciting clinical avenue of exploration.79
TRAMADOL
Tramadol is a weak opioid analgesic but also facilitates the release of noradrena-
line and serotonin in the descending inhibitory pain pathways of the spinal
cord. Tramadol binding to the mu-opioid receptor is 6000 times weaker than
that of morphine, therefore its analgesic action is likely to be predominantly
monoamine related.80 It is used as a step-2 option on the WHO analgesic ladder.41
Its efficacy may be similar to codeine (it is a synthetic analogue of codeine). It
may have efficacy in neuropathic pain,15 though it is used widely as a general
analgesic. Convulsions have been reported in those with a history of epilepsy,
those on high dosage or those using it in combination with other psychotropics
such as SSRIs and TCAs.80 Sedation is rare. Abuse potential is very low, as are the
risks of dependence and tolerance.80 There has been very widespread use of this
compound, and its safety appears well established. Drug interactions can occur
with concomitant use of cytochrome P (CYP)3A4 inducers (e.g. carbamazapine),
and serotonin enhancers (monoamine oxidase inhibitors [MAIOs]). Interactions
with SSRIs may cause serotonin syndrome; however, this appears to be rare in
clinical practice.
Non-opioid analgesics
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)
NSAIDs are particularly indicated for boney pain and do have some opioid-
sparing activity. NSAIDs inhibit platelet aggregation. SSRIs affect platelet
function, thus the combination may enhance the risk of gastrointestinal bleed-
ing. Prostaglandins play a role in memory consolidation, and subjective cognitive
impairments have been anecdotally reported with NSAIDs. These deficits are
subtle and only recognised in a small minority. They are probably not of clinical
significance.
ANTIDEPRESSANT MEDICATIONS
The use of antidepressant medications in a wide variety of chronic pain syn-
dromes, including cancer and neuropathic pains, is usual clinical practice.
Determining their actual effectiveness as co-analgesics is difficult. At least a
third of patients with neuropathic pain who take tricyclic antidepressants obtain
moderate pain relief or better.81 TCAs are effective for post-herpetic neuralgia.82
The number needed to treat (NNT) to achieve at least 50% pain relief compared
to a placebo is about 3.81 Similar efficacy has been shown in diabetic neuropa-
thy, atypical facial pain and post-stroke pain.82 They do appear to have analgesic
effect independently of their action on mood.83 Venlafaxine has been shown to
have similar effectiveness to tricyclics.81 There is very limited evidence SSRIs are
effective co-analgesics.81 The median required dosage is lower than the usual
dosage required to treat major depression, and the onset of action occurs faster
(1–7 days).82 That antidepressants are more effective for ‘burning’ pain than
for ‘shooting’ pains has been dismissed.61 The different TCAs do not exhibit
different analgesic efficacies.82 Amitriptyline is the most commonly used TCA,
nortriptyline has the least adverse reactions and imipramine is the cheapest. The
primary problem with the use of TCAs is their adverse effect profile.15 Caution is
required in those with cardiovascular histories, glaucoma, urinary retention and
autonomic neuropathy. Particular sensitivity to the adverse effects of antidepres-
sant medications is known to occur in pain patients. They may cause balance
problems (a threefold increase in rate of falls) and cognitive impairment because
of their anticholinergic effects. About one-third of medically ill patients have to
withdraw from TCAs because of intolerable adverse reactions,84 and about 20%
who take antidepressant medications for pain discontinue them.81 Amitriptyline,
the most toxic (even at low dosage), is metabolised to its active component,
nortriptyline. Nortriptyline is a very much more tolerable drug and equipotent
to amitriptyline in post-herpetic neuralgia. Very low dosage (e.g. 5 mg nocte)
should be introduced and gently titrated upwards over several weeks to 25–50 mg
nocte. The antidepressant range of nortriptyline is 50–100 mg. Serum drug levels
of nortriptyline, but not the other dirtier TCAs, are accurate and can be useful
in determining toxic doses (and therapeutic doses in depression treatment).
Mirtazapine, with its sedating properties, and venlafaxine, which is broad-
spectrum in action, are increasingly used for depression and pain indications.
Putative mechanisms of action include direct action on monoamine transmit-
ters enhancing inhibitory pathways, adenosinergic effects and antihistaminic
effects. Low dosage regimes and rapid onset suggests the possibility of a direct
analgesic action. Definitively diagnosing major depressive episodes in the pres-
ence of pain is difficult. Their usefulness in neuropathic pain may be accounted
for by the effects on sleep. ‘Improved sleep may be a huge bonus’.82 No com-
parative trials of TCAs and an effective hypnotic have been published. The
considerable therapeutic faith placed in TCAs as adjuvant analgesics may be an
expression of our desperation in managing difficult pain. It is clinically conven-
ient to offer another medication trial rather than admit therapeutic defeat in the
face of such terrible torment.
ANTICONVULSANT MEDICATIONS
These may be used as co-analgesics in neuropathic pain. Anticonvulsants can
cause significant cognitive adverse reactions, predominantly a consequence of
their sedative effects. At high dosage, ataxia and cognitive impairment (in the
elderly) may be induced. Because of the need to slowly escalate the dosage, a
therapeutic trial of up to 2 months is advisable. Carbamazepine, sodium val-
proate, phenytoin and lamotrigine have limited proven efficacy.
CALCIUM CHANNEL ALPHA-2-GAMMA LIGANDS (GABAPENTIN,

PREGABALIN)
These may be used as co-analgesics in neuropathic pain. Gabapentin, the
best-studied of the anticonvulsants for neuropathic pain, is effective at high
dosage (3600 mg/day) in post-herpetic neuralgia and diabetic neuropathy.85 In
uncontrolled trials, positive effects on other neuropathic pain syndromes were
demonstrated. Gabapentin is less effective than opioids in neuropathic pain.13
Tolerability is good, though drowsiness may occur, particularly if dose escalation
is rapid. Gabapentin is now considered a first-line medication for neuropathic
pain.
KETAMINE
Burst subcutaneous (or oral) ketamine may be used as an analgesic for neuro-
pathic and inflammatory pain, and to reset opioid receptors in high-dose opioid
regimes. An NMDA receptor antagonist, ketamine, at subanaesthetic doses
blocks the effects of the main excitatory transmitter in the CNS, glutamate. The
phenomenon of opioid ‘wind-up’ or central sensitisation (rapid opioid escala-
tion with diminishing responsiveness) may be arrested by pulses of ketamine.
‘Wind-up’ refers to the triad of allodynia, hyperalgesia and prolongation of the
pain response (failing opioid responsiveness). The commonest adverse reactions
of ketamine are psychiatric – vivid dreams/nightmares, dissociative sensations
(such as feeling detached from one’s body, misperceptions), dysphoria, visual hal-
lucinations and, rarely, delirium. These adverse reactions are rare with the minute
doses used for palliative care indications, and the warning that ketamine should
be used with caution in those with a psychiatric history is probably overstated.
Dose reduction and/or the introduction of as required midazolam (5 mg SC Stat)
or haloperidol (2–5 mg PO/SC Stat) contain these adverse effects. Clozapine may
be more effective than haloperidol at blunting the NMDA antagonist-induced
psychosis in schizophrenic patients administered ketamine.86 Amantadine or
opioid rotation with methadone, both of which have NMDA antagonism, may be
alternatives in those with fragile mental states and who are in need of addressing
paradoxical pain syndromes. Chronic ketamine abuse may result in cognitive
decline and dysexecutive symptoms.
PSYCHOSTIMULANTS
Psychostimulants, because of their arousing action, can reverse opioid-induced
sedation, thereby allowing an increase of opioid if necessary. Indirectly, they
enhance analgesia. Only at very high dose (100–300 mg amphetamine) are they
liable to induce psychosis. A past history of psychosis is a relative contraindica-
tion to their use. At methylphenidate doses of less than 1 mg/kg it is unlikely that
psychiatric adverse reactions, including dependence, will result.
BENZODIAZEPINES
The hypnotic qualities of benzodiazepines tend to fade after several weeks of
regular use. They hasten the onset of sleep and prolong the phase of light sleep,
hence increasing total sleep time. Non-benzodiazepine hypnotics such as zopi-
clone and zolpidem are preferred as these cause fewer changes in the sleep stages.
They also act upon the GABA receptor, and their mechanism of action is similar
to that of benzodiazepines. The differences may be related to dose and half-life of
the respective compounds. Clonazepam, for its anticonvulsant properties, may
be a tolerable option for neuropathic pain. In this instance, tolerance does not
usually occur, and a stable dose should remain therapeutic.
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palliative care by substitution with infusion of oxycodone. J Pain Symp Manage. 1996;
12: 182–9.
78 Olofsson CH, Ekblom A, Ekman-Ordeberg G, et al. Lack of analgesic effect of systemi-
cally administered morphine or pethidine on labour pain. Br J Obstet Gynaecol. 1996;
103: 968–72.
79 La Vincente SF, White JM, Somogyi AA, et al. Enhanced buprenorphine analgesia with
addition of ultra-low-dose naloxone in healthy subjects. Clin Pharmacol Ther. 2008; 83:
144–52.
80 Bamigbade TA, Langford RM. The clinical use of tramadol hydrochloride. Pain
Reviews. 1998; 5: 155–82.
81 Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev.
2007; 4: CD005454. DOI: 10.1002/14651858. CD005454.pub2.
82 McQuay HJ, Moore RA. Antidepressants and chronic pain. BMJ. 1997; 314: 763–4.
83 Max MB, Lynch SA, Muir J, et al. Effects of desipramine, amitriptyline, and fluoxetine
on pain in diabetic neuropathy. N Eng J Med. 1992; 326: 1250–6.
84 Popkin M, Callies A, Mackenzie T. The outcome of antidepressant use in the medically
ill. Arch Gen Psychiatry. 1985; 42: 1160–3.
85 Mellegers MA, Furlan AD, Mailis A. Gabapentin for neuropathic pain: systematic
review of controlled and uncontrolled literature. Clin J Pain. 2001; 17: 284–95.
86 Malhotra AK, Adler CM, Kennison SD, et al. Clozapine blunts NMDA antagonist-
induced psychosis: a study with ketamine. Biol Psychiatry. 1997; 42: 664–8.
CHAPTER 7
Other symptoms and the psyche
The brain and the mind affect and are affected by the systemic symptoms of
advanced malignancy.
PRURITIS
Pruritis (itch) is an unpleasant cutaneous sensation which provokes the pleas-
urable desire to scratch.1 Cough can be considered as a respiratory itch. Like
pain it serves a protective function. It can be conceptualised as a type of pain.
A subgroup of C-fibres are preferentially excited by pruritic compounds, how-
ever, and may be a dedicated neuronal system for itch.2 Released histamine and
other pruritogens provoke the motor response of scratching, and serotonin is
involved as a mediator. Itch is a common symptom in advanced malignancy. It
may accompany cholestasis and uraemia. It frequently occurs in blood disorders
and HIV/AIDS. Cytokines released by tumours may provoke itch, and peripheral
nerve lesions may induce it. Local factors such as dry skin may contribute to
pruritis, though central influences are important. Psychological and psychiatric
influences are clinically relevant. Medications are more often the cause than the
cure of itch. Generalised itch occurs in about 1% of those receiving oral opio-
ids, and at considerably greater frequency in those on parenteral opioids.3 This
appears to be a central effect. Mu receptors mediate itch, and kappa receptors
block itch. This adverse effect is usually self-limiting.
Topical treatments of itch – emollients, cooling, calamine, antihistamines,
capsaicin – may be of only limited value. Systemic treatment with the older
generation of antihistamines (e.g. promethazine) can result in overseda-
tion. Antidepressant medications, particularly doxepin (a crude but effective
antihistamine-like tricyclic) and paroxetine, can be helpful for weeks to months,
but efficacy tends to fade. Paroxetine, at low dosage, seems more effective than
other SSRIs, for unknown reasons. Mirtazapine may have a role in managing
itch, and opioid antagonists decrease scratching in cholestatic itch and severe
uraemia. Opioid antagonists are potent antipruretic drugs but interfere with
analgesic control.4 Corticosteroids are often empirically trialled. Pruritis is
85
disturbing and distressing. If persistent, like pain, it tends to induce negative

affect and cognitions.
FATIGUE/ASTHENIA
If I had strength enough to hold a pen, I would write how easy and pleasant
a thing it is to die.
William Hunter (1718–83)5
Fatigue is the commonest symptom experienced during the course of cancer,

with prevalence estimates of greater than 70–80%. Often not volunteered but
upon asking, most cancer patients, as well as those with neurodegenerative
disorders, complain of this debilitating symptom. Lay terms include tiredness,
exhaustion, lethargy, weakness and lack of energy. If cancer-related, this symp-
tom may be described as ‘weakness’, and if a symptom of depression or anxiety
as ‘fatigue’ or ‘lack of energy’.6 However, word descriptors are likely culturally
and linguistically variable. Fatigue is difficult to quantify. It is entirely a subjec-
tive symptom. It is not the same as muscle weakness, rather it is difficulty in
the initiation, or sustaining, of voluntary activities.7 The medical term asthenia
includes fatigue, generalised weakness and mental fatigue. It refers to decreased
capacity to maintain adequate performance (tiring easily), difficulties initiat-
ing activity, impaired concentration and memory, and emotional lability.8 Poor
concentration, forgetfulness, making slips of the tongue and being unable to
find the correct word are typical subjective complaints of tired persons, yet on
formal neuropsychological testing objective deficits are not usually confirmed.9
With advancing disease, fatigue tends to progress to such an extent that it pre-
cludes independent functioning. The concept of ‘vital exhaustion’, initially used
in cardiology,10 aptly describes terminal fatigue.
Fatigue may be caused directly by the disease and indeed many patients
attribute their fatigue to the cancer ‘stealing’ their energy. Damage to the nerv-
ous system results in profound fatigue, for the system is required to function
at maximal capacity to cope with routine life tasks. Therapeutic ‘poisons’ such
as chemotherapy and radiotherapy are potent causes of fatigue as are the array
of medications with sedating side effects. Tiredness is a sign of depression,
a consequence of insomnia and a symptom of anxiety and worry. Clinically
differentiating depression and fatigue is difficult.11 The affective and cognitive
symptoms differentiate them, but the physiological symptoms do not. There is
overlap of symptoms between depression and fatigue. Neurasthenia is being
reconsidered as a psychiatric syndrome for this reason. Fatigue is a cardinal
symptom of anaemia and a clinical indicator of the need for blood transfusion.
OTHER SYMPTOMS AND THE PSYCHE 87
Physical disuse reinforces fatigue, and fatigue discourages activity. This vicious
cycle not only undermines physical functioning, it erodes emotional well-being,
and immobility encourages psychological regression (see Chapter 3).
Occasionally, the cause may be reversed, but more commonly therapeutic
endeavours fail. The important exception is if fatigue is symptomatic of depres-
sion. Some activity should be encouraged. Physiotherapy may be useful both
functionally and psychologically. Corticosteroids may be trialled, and temporary
respite can be achieved. Corticosteroids are perhaps best reserved for facilitat-
ing energy for an important occasion because of the risk of long-term adverse
effects. Psychostimulants, modern day ‘tonics’, can be beneficial particularly in
the earlier stages before the disease process has ‘run down’ the dopaminergic
neurotransmitters. Despite large placebo effects and few large scale trials, there
is evidence emerging that methylphenidate and modafinil may be of some
effectiveness,12 though the optimal dose is uncertain,13 and not all trials are sup-
portive.14 If there is a clinical suspicion of major depressive disorder, the most
activating of the antidepressant medications is bupropion.
Wretched as fatigue is, particularly to those who have led a physically active
lifestyle, it does have protective and adaptive functions. By limiting the capacity
to overexertion and overwork, fatigue serves to biologically retain some reserve
of energy. Psychologically, fatigue instructs the reluctant victim that physically
they are not immortal, and that despite their hope to the contrary, death is
approaching. Denial is challenged by this symptom. Appropriate dependency is
enforced. A gradual withdrawal of attachment commences as the patient ceases
to have the energy to participate in family and society events. A proclamation of
surrender and a covenant of acceptance are provoked by vital fatigue.15
NAUSEA AND VOMITING

Nausea is one of the most frequent and unpleasant symptoms associated with
advanced malignancy and is often undertreated.16 It is often the symptom of
multiple pathological insults and in terminal care usually the causes are irrevers-
ible.16 The main clinical syndromes (and aetiologies) of nausea and vomiting
in terminal cancer are: gastric stasis, biochemical (toxins, medications), raised
intracranial pressure, vestibular, bowel obstruction and anxiety.16 Central
structures involved in nausea, such as the chemoreceptor trigger zone and the
‘vomiting centre’ in the medulla, are vulnerable to emotional influence. In the
last weeks of life, 80% of cancer patients require pharmacological interventions
for nausea.
Derived from the Greek term for seasickness, nausea is ‘a feeling of sickness
with an inclination to vomit’. The term is not necessarily widely known in the
general community, but the ‘feeling of wanting to vomit’ and similar terms are.
Retching and vomiting may provide temporary relief from nausea. Nausea is
often accompanied by autonomic arousal. Drowsiness is an associated symptom,

and relief of nausea may enhance alertness. The malaise, dysphoria and apathy
of motion sickness are known to us all. Anxiety is both a consequence of, and
an aggravating influence on nausea.17 It is underappreciated that nausea may be
a symptom of a major depressive episode, particularly in the elderly.17
The clinical characteristics of nausea and vomiting suggest the most likely
intervention. Stretching and irritation of the gut wall by tumour or gastroparesis
can cause nausea, precipitated and aggravated by nutritional sensory stimuli. Thus
management of ‘gut-related’ nausea involves avoiding and minimising olfactory
and food cues. Acupressure at P6 (just above the wrist) may assist, though acu-
pressure wristbands have been shown not to be effective.18 Constipation should
be attended to. Prokinetic medications (orally if tolerable, otherwise parenter-
ally) may be helpful. Most anti-emetic medications are psychoactive, exerting
their actions on dopamine (mainly the D2 receptors), histamine, serotonin and
acetylcholine receptors. Adverse effects of these central acting medications are
to be expected. Metoclopramide, the drug of choice for ‘gut-related’ nausea, can
induce acute dystonic reactions, most commonly in young adults. Akathisia may
occur with prolonged use. Metoclopramide is often not registered by clinicians as
being a phenothiazine, and its potential to cause neurological adverse effects is
not considered. Domperidone has similar prokinetic action, but because it does
not cross the blood–brain barrier it does not cause neurological adverse effects.
Levomepromazine is sedating and liable to induce postural hypotension and
extrapyramidal adverse effects in the elderly and the frail. Anticholinergic and
antimuscarinic medications such as these anti-emetics are prone to exacerbate
cognitive difficulties.
Opioid-induced nausea, which occurs in 10–40% of patients at the com-
mencement of opioid therapy, is most common with morphine and is generally
relieved with central acting D2 antagonists such as haloperidol (at dosages of less
than 1–2 mg). Prophylactic anti-emetics are not required, but should be easily
accessed if needed. Semi-synthetic opioids are less inclined to induce nausea.
For most this nausea is a self-limiting symptom, and within days to weeks toler-
ance develops.18
Motion-induced nausea, a conflict between visual and vestibular sensors, can
worsen rapidly (the avalanche syndrome) and be mercifully relieved by vomiting.
Females suffering gynaecological cancers are at particular risk for this variant of
nausea. This type of nausea is the most vulnerable to psychological influences,
particularly expectation. Motion sickness can reduce pain sensitivity in a way
analogous to stress-induced analgesia.19 In addressing motion sickness, adequate
analgesia is necessary and this may need to be administered parenterally until
control is regained. Attending to the mismatch between visual and vestibular
information is difficult, if not impossible, as the movement inducing the nausea
is commonly as simple as altering body posture in bed. Cyclizine and hyos-

cine, usual medications of early choice for motion sickness, may be sedating.
Because levomepromazine hits multiple receptors it can be effective. Adventure
sportsmen, at high risk for motion sickness, tend to opt for the phenothiazine
antihistamine drug promethazine. Interestingly, after about 5 days at sea, seasick-
ness usually resolves spontaneously. This is not necessarily so for space sickness
nor for the nausea of advanced disease. For several days after return to land,
seasickness may resurge (mal de débarquement). It is therefore clinically sensible
to be patient and cautious, for successful relief of motion sickness may take sev-
eral days to ‘bed-down’. Habituation does not appear to occur in cancer-related
nausea, unlike seasickness. Fear and expectation seem more potent behavioural
influences than desensitisation. Acupuncture and diet have no scientific support
as interventions.20 Gastric stasis can be produced by motion sickness, resulting
in secondary ‘gut-related’ nausea and poor oral absorption of anti-emetics.20
Around-the-clock administered anti-emetics are usually required. At least
one-third of nauseous patients require multiple anti-emetics. The pharmacol-
ogy of treating this symptom can easily become complicated. The most effective
of the anti-emetics is a corticosteroid,21 but this exposes the patient to many
potential adverse effects, especially if long-term use is necessary. Serotonin
(5HT3) antagonists such as ondansetron are usually ineffective, but not invari-
ably so. Benzodiazepines and phenytoin can be effective.20 Neurokinin-1 receptor
antagonists may find a role in palliative medicine. Managing nausea is ‘trial and
error’ pharmacotherapy. Palliative sedation is rarely required for intractable
nausea and vomiting.18
Anticipatory nausea and vomiting is triggered by in vivo exposure to certain
stimuli associated with the administration of chemotherapy. It is a conditioned
response and is amenable to behavioural intervention. Undoubtedly a concern-
ing problem in oncological practice, it is of lesser relevance in palliative care.
ANOREXIA AND CACHEXIA
When thou dost feel creeping time at thy gate, these fooleries will please
you less: I am past my relish for such matters. Thou seest my bodily meat
doth not suit me well: I have eaten but one ill-tasted cake since yesternight.
Queen Elizabeth I (1533–1603)22
Diminishing and changing taste sensation and appetite occur in most advanced
cancer patients. The causes are multiple. It is important to exclude depression as
a cause, for this is potentially treatable. Attention to oral hygiene, small attractive
meals and appetite stimulants may be of benefit. High-calorie food supplements
are frequently advised but are of limited value aside from their psychological
punch (often for the relative rather than the patient). Corticosteroids, prokinetic
agents and psychostimulants may be trialled, though their value is questionable.
Paradoxically, psychostimulants in the medically ill enhance appetite, whereas in
the healthy they may be used and abused in order to lose weight. Progestogens
are favoured by some, though evidence of efficacy is lacking. A small amount of
alcohol prior to a meal may encourage appetite. Patients in the advanced stages
of cancer often use the phrase ‘fed-up’ to describe this state, as if to suggest their
appetite is satiated and they have no physiological need of food (despite the
wasting). This contrasts sharply with the high rate of hospitalised elderly with
critical non-malignant illnesses who are malnourished and interested in food.
The metabolic mechanism of the progressive wasting in advanced cancer and
AIDS patients is uncertain. Cytokines are implicated. Cachexia is not starvation,
and parenteral feeding does not reverse it. There are no effective treatments,
though many approaches are usually tried. It is distressing for the patient to
experience the withering loss of their familiar body shape and their strength.
The changing body image challenges self-esteem (see Chapter 3). Sharing food
with others is a social event, an important opportunity for communication, and a
mode of expressing personal and cultural customs. Preparing food has immense
communication and caring value. These losses for the cachectic patient may
marginalise them, alienate them from their culture and deprive them of that
precious time with others. Cachexia advertises sickness and dying.
DYSPNOEA
Advanced cancer is commonly associated with dyspnoea, affecting perhaps
50%. Fears of inability to breathe and suffocation are difficult to manage, for
respiratory failure is a feature of many terminal illnesses. It is a particular fea-
ture of advanced motor neurone disease. Difficulties acquiring sufficient oxygen
activate the Hering–Breuer reflex, resulting in rapid, shallow breathing. This is a
physiological attempt to compensate. However it also provokes anxiety, which,
if intense, will undermine breathing efficiency. Posture, relaxation exercises,
distraction and a fan blowing cool air at the face may be of benefit in the early
stages. By consciously focusing on slowing the breathing rate, thereby enhancing
its efficiency, the anxiety of respiratory distress may be eased. Hypoxia may be
eased by oxygen therapy, at least transiently, provided the patient is not tolerant
to carbon dioxide respiratory drive. Psychological dependency on oxygen, and
the awkward and potentially dangerous equipment necessary, are important
issues needing to be considered prior to providing this treatment. Sleep is invari-
ably disrupted by dyspnoea, for both physiological and psychological reasons.
In sleep, respiratory performance falls and these patients can’t afford for this to
occur. It is slightly more common to die at night, and fears of not awakening
are not surprising. This may be of comfort to some, but disturbing to those
not as yet accepting. Opioids and benzodiazepines can be most helpful in the
advanced stages of respiratory failure, by slowing rate and relieving anxiety.
Respiratory depression and hypercapnia are relative considerations only. Pain
tends to protect against opioid-induced respiratory depression, and by this stage
of illness most have current exposure to opioid medication. Symptom relief is
a more pressing concern. The mechanism of opioids in this clinical situation is
uncertain. Probably opioids function predominantly as anxiolytics. They may
reduce the sensitivity of the ‘respiratory centre’ to oxygen and carbon dioxide
stimulation, thereby slowing respiratory rate. Oral benzodiazepines, in contrast
to parenteral benzodiazepine in the naive patient, have not been shown to
adversely affect respiratory function. Chlorpromazine and buspirone have also
been used for these symptoms.
Air hunger invokes distress. It may be that the attending relatives are more
distraught by this than the patient. It is unlikely that sufficient consciousness
is retained for a patient to be disturbed by Cheyne–Stokes respiration and
the ‘death rattle’. It is important to note that while it is preferable to introduce
anticholinergic medications early for retained salivation in those too weak to
expectorate, such agents are potent precipitators of delirium. Glycopyrronium
has a less delirogenic potential. Helpless relatives require reassurance and edu-
cation regarding these disturbing physiological events. Profound and acute
dyspnoea may be an indication for terminal sedation (see Chapter 10).
REFERENCES
1 Haffenreffer S (1660). From: Rothman S. Physiology of itching. Physiol Rev. 1941; 21:
357–81.
2 Schmelz M. Itch and pain. Neurosci Behav Rev. 2010; 34: 171–6.
3 Twycross R, Greaves MW, Handwerker H, et al. Itch: scratching more than the surface.
Q J Med. 2003; 96: 7–26.
4 Reich A, Szepietowski JC. Opioid-induced pruritis: an update. Clin Exp Dermatol. 2010;
35: 2–6.
5 Hunter J. Quoted in: Gloyne SR. John Hunter. Edinburgh: E & S Livingstone; 1950.
p. 88.
6 Hauser K, Rybicki L, Walsh D. What’s in a name? Word descriptors of cancer-related
fatigue. Palliat Med. 2010; 24: 724–30.
7 Chaudhuri A, Behan PO. Fatigue in neurological disorders. Lancet. 2004; 363:
978–88.
8 Watanabe S, Bruera E. Anorexia and cachexia, asthenia and lethargy. In: Cherny NI,
Foley KM, editors. Pain and palliative care. Hematol Oncol Clin North Am. 1996; 10:
189–206.
9 Moss-Morris R, Petrie K, Large R, et al. Neuropsychological deficits in chronic fatigue
syndrome: artefact or reality? J Neurol Neurosurg Psychiatry. 1996; 60: 474–7.
10 Appels A, Mulder P. Excess fatigue as a precurser of myocardial infarction. Eur Heart J.

1988; 9: 758–64.
11 Reuter K, Harter M. The concepts of fatigue and depression in cancer. Eur J Cancer
Care. 2004; 13: 127–34.
12 Brietbart W, Alici Y. Psychostimulants for cancer-related fatigue. J Natl Compr Canc
Netw. 2010; 8: 933–42.
13 Hardy JR, Carmont S-AS, O’Shea A, et al. Pilot study to determine the optimal dose
of methylphenidate for an n-of-1 trial for fatigue in patients with cancer. J Palliat Med.
2010; 13: 1193–7.
14 Moraska AR, Sood A, Dakhil SR, et al. Phase III, randomised, double-blind, placebo-
controlled study of long-acting methylphenidate for cancer-related fatigue: North
Central Cancer Treatment Group NCCTG-N05C7 trial. J Clin Onc. 2010; 28: 3673–9.
15 Nunez Olarte JM, Dickerson ED. Asthenia: is it more than a symptom (Editorial). Prog
Pall Care. 2000; 8: 126–7.
16 Glare PA, Dunwoodie D, Clark K, et al. Treatment of nausea and vomiting in terminally
ill cancer patients. Drugs. 2008; 68: 2575–90.
17 Haug TT, Mykletun A, Dahl AA. The prevalence of nausea in the community: psycho-
logical, social and somatic factors. Gen Hosp Psychiatry. 2002; 24: 81–6.
18 Wood GJ, Shega JW, Lynch B, et al. Management of intractable nausea and vomiting
in patients at the end of life. JAMA. 2007; 298: 1196–207.
19 Drummond PD. Suppression of pain and the R2 component of the blink reflex during
optokinetic stimulation. Cephalalgia. 2004; 24: 44–51.
20 Golding JF, Gresty MA. Motion sickness. Curr Opin Neurol. 2005; 18: 29–34.
21 Glare P, Pereira G, Kristjanson LJ, et al. Systematic review of the efficacy of antiemetics
in the treatment of nausea in patients with far-reaching cancer: a review. Support Care
Cancer. 2004; 12: 432–40.
22 Harrington J. The Letters and Epigrams of Sir John Harington: together with the Prayse
of Private Life. McClure NE, editor. Philadelphia, PA: University of Pennsylvania Press;
1930. p. 97.
CHAPTER 8
Depression
My body is sick but my mind is worse, engrossed in gazing endlessly upon

its suffering.
Ovid (43 BC–17 AD)1
The word ‘depression’ has changed its meaning over recent decades. In colloquial
use it means sadness. The older term, ‘melancholia’, is an awkward term and
unlikely to assume common use. Clinical depression or major depressive disor-
der (MDD) is the medical term used to refer to the disease ‘depression’. While a
common disorder in the general community, and not surprisingly more preva-
lent in the sick, depression has assumed over recent decades greater familiarity. It
is generally accepted that depression is underrecognised and undertreated in the
terminally ill, more so in non-malignant forms of terminal illness.2 Increasing
public and professional knowledge about the illness and tolerable medication
options, however, risk overdiagnosis and overtreatment of this disorder in the
general community.
Depression is not the inevitable consequence of misfortune or severe illness.
It is a serious and manageable disorder that needs to be recognised and treated.
Clinical depression is distressing and emotionally painful. It lowers the pain
threshold, it may reduce survival in cancer patients by interfering with treatment
compliance and immunological parameters, it precipitates early admissions to
palliative care facilities for it reduces the ability to self-care, and suicide is a pos-
sible consequence of the illness. In addition to the immense suffering associated
with depression, it can impair cognition and distort decision-making ability.
Depression erodes the quality of remaining life. Major depression is treatable.
In the general population the success of combined antidepressant and psycho-
therapy is 85%.3 While likely to be more difficult to treat in a physically unwell
person, depression clearly warrants considerable attention as a symptom and
syndrome in the dying.
93
The relationship between cancer and depression may be bidirectional.

Depression can be an early or occult symptom of a malignancy, and is a common
complication of cancer. Studies of mood and stress (particularly social support)
adversely influencing immune status and increasing cancer risk are conflicting,
but appealing.4,5
SADNESS AND GRIEF

Sadness is the normal response to loss. Waves of sadness, perhaps cued by some
reminder, interrupt and transiently unsettle. Sadness is not persistent and over
time its viciousness abates. Grief is the psychological process initiated by the
death of a loved and attached person (see Chapter 4). Anticipatory grief refers
to the psychological work of the dying emotionally and cognitively prepar-
ing for loss of life. Most find this difficult. As symptom burden increases, and
fate becomes clearer, this may serve to encourage this unenviable task. Gentle
reminders, even confrontation, may be helpful, though some can’t or won’t
prepare for death and die fighting the reality of nature. The offering of end-
less, increasingly futile, oncology treatment options or an unflinching faith in
alternative medicine may hamper this process. Therapeutic moments to address
anticipatory grief issues occur in the shower, changing dressings, chatting about
life experiences or tidying up the room. The stilted and artificial situation of an
office-based session of grief counselling is rarely ideal. Not only does good prepa-
ration appear to ease some of the anxieties for the dying, it provides the loved
ones opportunities to embark, with initial assistance, on their journey of grief.
DIAGNOSING DEPRESSION
A cankered soul macerated with cares and discontents.
Robert Burton (1577–1640)6
The symptoms of depression are affective, cognitive and somatic. Depression is

best conceptualised as a spectrum disorder, the symptoms ranging from mild
to very severe. As affect darkens, physical symptoms increasingly accompany
and cognitions blacken. The differentiation between reactive and endogenous
mood disorder is not particularly helpful. Negative life events may play a role
precipitating depression, however this is somewhat uncertain. They are probably
not more frequent than positive events precipitating a deterioration of mood.
The changing circumstances force adaptation, and it may be this that unsettles
mood equilibrium. The cause of depressive disorder is unknown. The inward
turning of anger (the psychoanalytic model), pervasive negative thinking (Beck’s
cognitive model), learned helplessness (a behavioural model) and depression
DEPRESSION 95
as a psychomotor disorder are useful theoretical concepts.7 The catecholamine

theory implicates biological changes, at least in severe depression. In cancer
patients cytokines may play a role.8 Mild depression may be a purely cognitive
disruption, but with severity biology becomes progressively more relevant. There
is a ‘grey’ zone along the spectrum where psychological and psychophysiological
depressions merge. Clinical depression is a misery of mood. The sufferer perva-
sively feels low-spirited, negative, pessimistic, lacking of enjoyment, incapable
of pleasure, ruminative and worthless. Every moment the sufferer feels gloomy,
sometimes (often early morning) more than at other times. Sadness is a fre-
quent symptom, though not all acknowledge sadness. By diagnostic definition
depressive symptoms need to persist for at least 2 weeks before being consid-
ered a disorder. It is not sensible clinical practice to diagnose depression on
a single occasion. Reviewing on another occasion, perhaps the following day,
provides a gauge of psychological reactivity and assists in differentiating major
depression and sadness. Anhedonia and loss of interest in others, and in life,
are prominent features. The patient becomes immersed in his or her own grim
space. They ‘hibernate’, away from social contact. The future as perceived by the
patient is beyond appreciation, for the present is so unbearable. Humour may
not be lost, for much humour is indeed ‘black’. The examiner may be ‘touched’
by the patient’s sense of utter helplessness, this being a useful intuitive diagnostic
indicator for experienced practitioners. Thoughts become muddy and sticky,
self-centred and preoccupied with bleakness. Requesting euthanasia or accepting
very high-risk treatment interventions may be indicative of this objectionable
existence. Negativistic and nihilistic ideations and delusions may occur in severe
depressive states. The pain of the emotions and thoughts of depressive disorder
is so profound that self-destruction may emerge for the sufferer as a relieving
and respectable option. The lifetime risk of attempted suicide of those suffer-
ing major depression is 25–50%. Intriguingly, in Cotard’s syndrome, a rare and
severe psychotic depression, mood can paradoxically appear jovial despite the
patient believing they ‘no longer (deserve to) exist’. Life, to their great relief, has
ended. A similar paradoxical affect may be observed in those patients who have
formulated a definite plan to end their life, and in those physically recuperating
following a suicide attempt. This seemingly improved mental status tends to
persist only a few days before the misery resurfaces. In advanced stage cancer
the prevalence of major depression appears to fall (though distress increases).9
Direct questioning of suicidal ideation and plans is essential, yet is by no means
a guarantee of intent. In many ways, such intrusive interrogation is similar to a
thorough physical examination. The patient is assured that their symptoms are
being properly assessed.
Acquiring a history, a narrative, is an underrated task in modern clinical
medicine. It is the most valid assessment strategy. Information concerning the
evolution of symptoms, past history and family history of affective disorder,

substance use and medications is crucial. Obtaining corroborative information
from important others (including attending health professionals) always assists,
and in the frail terminally ill may be the only available option. The recognition of
only 40% of depressions in cancer patients in the 1980s,10 a reflection of similar
difficulties in the general community, may have improved over recent decades.
The reluctance of patients to disclose distress, for they assume that nothing
could be done to alleviate it, or they don’t wish to seem ungrateful, is undoubt-
edly a barrier hindering diagnosis.11 The frank avoidance of medical staff asking
about emotions (for fear of causing harm or being personally affected) and their
distancing from the patient by presuming that the patient’s emotional status is
appropriate to their situation, by strategies such as premature reassurance or
a change of topic, reduces the prospect of a psychiatric diagnosis.11 A more-
recently acquired distancing strategy is that of a tearful patient being promptly
prescribed antidepressant medication and dismissed.
TABLE 8.1 Major depressive disorder/dysthymia
Major depressive disorder Dysthymic disorder

Symptom present >2 weeks Symptom present >2 years
Depressed mood Depressed mood
Insomnia (early morning awakening) Insomnia (initial)/hypersomnia
Fatigue Fatigue
Poor concentration/decision-making Poor concentration/decision-making
Anhedonia/loss of interest
Weight loss (>5%)
Psychomotor retardation/agitation
Worthlessness/guilt
Suicidal ideation
Low self-esteem
Hopelessness
Antidepressant medication responsive
The criteria-based signs and symptoms of MDD (see Table 8.1, DSM-IV) are
not so applicable to the medically ill. The core affective symptoms are depressed
mood and anhedonia. The somatic symptoms such as insomnia, anorexia,
cachexia, fatigue and motor retardation are less diagnostically discriminative
in the physically ill. The diagnosis in cancer patients rests upon the presence of
affective and cognitive, rather than somatic, symptoms (see Box 8.1). The patient
may be tearful, withdrawn, isolative, irritable and dismissive, and rejecting of
attempts at establishing any human contact. And they may also be in pain. In
DEPRESSION 97
BOX 8.1 Affective and cognitive symptoms of major depression
● Dysphoric/depressed mood and affect

● Anhedonia
● Loss of interest/apathy
● Poor concentration/attention/memory
● Slowed/sluggish thoughts
● Pessimism/negativity
● Worthlessness/feeling a burden on others
● Excessive guilt
● Helplessness
● Hopelessness
● Suicidal ideation
the medically ill, the severity of the depression is not directly correlated with
physical severity. About 10% of depressive illness has reverse or negative symp-
toms, such as overeating and hypersomnia. This hibernatory-type presentation
is frequently missed. Age and sex influence the presentation of depressive
symptoms. Behaviourally disruptive young children, withdrawn and irritable
adolescents, anxious young women, aggressive men and cognitively slowed
elderly portray the vast and varied pattern of affective disorders. Depression
is by no means necessarily an easy diagnosis. The most widely used self-report
measure of depression is the Hospital Anxiety and Depression Scale (HADS),
which is a relatively easily administered tool. The Beck Depression Scale and
many other scales tend to lose reliability in the presence of coexistent physi-
cal illness. These instruments are certainly indices of general distress, and are
dependent upon the ability of the patient to respond to the questioning, but lack
specificity for diagnosing MDD. They are useful research tools, but of limited
assistance to the clinician. Not surprisingly, Cochinov has shown that a single-
item interview that asks ‘are you depressed’ is diagnostically of greater validity
(and should be a routine admission question anyway).12 Lloyd-Williams and
co-workers suggested that this question is culturally specific and does not have
the perfect sensitivity and specificity in the UK that it does in North America.13
But by adapting the actual word to the society in which one works, Cochinov’s
question remains a robust and clinically very useful screening and diagnostic
tool for MDD. ‘Miserable’, ‘black’, and ‘low’ tend to achieve similarly clinically
valid responses. The additional question, ‘Have you experienced loss of interest
in things or activity that you would normally enjoy?’ further improves diagnostic
sensitivity to around 90%.14 Co-opting the attention and cooperation of patients
to complete assessment tools is usually only acceptable and feasible in those with
mild to moderate disorder. In severe depression, the inability to perform such
requests may be diagnostically relevant. However, of greatest significance to the
clinician is the unproven relationship between these diagnostic tests and treat-
ment responsiveness. Being able to anticipate medication-responsive depression
is fundamentally what needs to be determined.
PREVALENCE
Depend upon it, Sir, when a man knows he is to be hanged in a fortnight, it

concentrates his mind wonderfully.
Samuel Johnson (1709–84)15
The current (1 month) prevalence of major depression in national epidemiologi-

cal studies in the USA, UK and Australasia is 3–5%.16 Depression is commoner
in women. Unipolar major depression in 1990 was the leading global cause of
life-years lived with disability, and the fourth leading cause of disease burden.
About one-quarter to one-third of medical inpatients and outpatients have some
symptoms of depression, though generally these are milder than the symptoms
encouraging presentation at a mental health service. The depression is severe
in 4–18%, often in the more severely ill. Depression may precede the physical
illness, more commonly it follows it.
A systematic review of the prevalence of depression in patients with advanced
cancer and among mixed hospice populations in 2002 commented on the poor
quality of available research.17 Prevalence ranges from 1% to 50% depending
upon methodological issues such as diagnostic criteria, method of diagnosis, the
threshold of diagnosis and the incorporation or not of minor (adjustment, dys-
thymic) states.18 From the clinician’s perspective, relevant information required
is whether or not antidepressant medications should be trialled. If affective
symptoms are to the right of centre of the spectrum, then medication is likely
to be appropriate. Minor depressions are unlikely to benefit from antidepres-
sant medication. The HADS gave a median prevalence of ‘definite depression’ of
29%.17 Using psychiatric interviews, the prevalence ranged from 5% to 26%, with
a median of 15%.18 ‘Depression’ frequently ranks in the ‘top 10’ symptoms in a
hospice checklist, and the probability is that a proportion of cases are missed.
Using stringent diagnostic criteria, 5–15% of cancer patients meet criteria for
MDD.12 These patients require medication as a component of the manage-
ment. A further 10–15% present with less severe ‘subthreshold’ depression, and
at least 25% of advanced cancer patients present with a significant degree of
DEPRESSION 99
dysphoria.18,19 It is important to acknowledge that despite some uncertainties

regarding exact prevalence, the vast majority of individuals with cancer do not
develop clinical depression.
The separation of early- and late-stage cancer populations significantly influ-
ences prevalence figures. The stage or phase of the malignant illness is relevant.
The major stress points during cancer are diagnosis, relapse, the introduction
or removal of therapies and the moving from the curative to palliative phase.
These periods are distressing, and potentially depressogenic. However, so too
may be the completion of a treatment modality, the consequential ‘abandon-
ment’ by these providers, and the anxious awaiting of the feared relapse. The
expected peak risk periods are early in the disease course, and late. There is an
accumulation in the advanced phase of disease- and treatment-related burdens
such as cytokine activity, physical frailty, chemotherapy side effects, corticoster-
oid administration, pain and anticipatory grief. Data suggests that depression
is commoner in the later stages of illness, with prevalence rates of 13–26%.19
However, in the terminal phase, depression may be less frequent, even unusual.
Conill surveyed by symptom questionnaire their subjects on two occasions, the
second within 7 days of death, and noted a fall in the rate of depression from
53% to 39%.20 Coyle retrospectively reviewed the files of 90 patients within 4
weeks of death by cancer, and noted that at 4 weeks 8% volunteered complaints
of depression, and that this fell to 4% at one week.21 Using DSM-III criteria, a rate
of MDD of only 3.2% was determined in 93 incurable and terminally ill patients,
in a palliative care unit, who died within 6 months of admission.22 Including
disorders in which depressive affect plays a prominent part (MDD, adjustment
disorders with depressed mood, minor depression), these authors observed only
a 10% prevalence. Excluding the patients with cognitive impairment resulted
in an overall prevalence of MDD of 6%.22 As death approaches perhaps the rate
of clinical depression actually falls, though not necessarily the rate of minor
depression (or sadness).9 Depressive disorder is only rarely encountered in the
dying, yet is common in the early and later phases of the cancer journey. Death
on the horizon may be therapeutic for mood. Whether the mechanism for this
is psychological or physiological, or both, is speculative. From an evolutionary
perspective, depression is adaptive in situations where continued effort will result
in either danger or loss of resources. Depressive symptoms inhibit challenging
behaviours and de-escalate the conflict. Fighting for life becomes a futile effort
and the ‘need’ to be depressed evaporates.23 When there is no perceived or actual
future, time is compressed to the immediate. Survival for the moment is the
overriding occupation.
The prevalence of depression in cancer patients has been lower during the last
two decades than previously.24 The speculative reasons for this are many, and the
finding is not convincing as yet.
RISK FACTORS
The aetiology of depressive illness is unknown. There are known factors which
seem to be of relevance. There are minor genetic vulnerability factors, and
psychological and physical stressors (see Box 8.2). That individuals become
clinically depressed in response to changeable life events is not scientifically
well established. The buffering effects of social support are difficult to prove.
Contrary to risk factors for depression in the general population, depression of
those with cancer may not be more prevalent in women and the aged. Depression
is three times more prevalent among North American cancer patients who
did not acknowledge their prognosis,25 but this could be a consequence of the
depression rather than a cause, for all would have been informed at some stage.
In an Indian study the reverse trend has been described.26 Particular diseases
and medications are known to enhance risk. Depression can be a direct conse-
quence of antineoplastic therapy. Among cancer patients the highest prevalence
rates are exhibited in those patients with pancreatic, oropharyngeal and (early)
breast cancers. Poorly controlled pain and increasing disease symptoms are
associated with more severe depressions. The factors lowering resilience to
depression cannot always be clinically identified. Depressive disorder is the final
common pathway of internal and/or external disruption to the nervous system.
Neurotransmitter derangements do occur, but may be ‘downstream’ effects. What
initiates this cascade of self-punitive biological events remains speculative. The
popular explanation that depression is a deficit of nerve chemicals is convenient
rather than convincing.
BOX 8.2 Risk factors for major depression
● Genetic (family history of affective disorder, alcoholism)

● Past personal history
● Advanced age
● Advanced disease
● Oropharyngeal/pancreatic/(early) breast cancer
● Physical immobility/dependency
● Poorly controlled pain
● Social isolation/few social supports
● Alcohol
● Concurrent severe medical illness
● Medications:
− corticosteroids
− anabolic steroids
− chemotherapy (vincristine, vinblastine, procabazine, interferons)
− beta-blockers (propranolol)
DEPRESSION 101
DIFFERENTIAL DIAGNOSIS
The overwhelming sadness of the predicament of many terminally ill, projected
onto the clinician, and the ill-informed carer’s viewpoint ‘that anyone in such
circumstances would be depressed’ may entice a relaxation of diagnostic rigour.
Grief reactions are associated with undulations of mood and depression with a
prostration of mood. Denial and manic defences, superficially protective to the
sufferer, may dissuade the interviewer of the intensity of underlying distress.
Adjustment disorder with depressed mood is a vague and impractical diagno-
sis. Chronic dysthymia, predating the cancer, may encourage the clinician to
formulate a depression diagnosis. Clinically differentiating ‘major’ and ‘minor’
depression is arbitrary at best. Uncharacteristic anxiety, particularly night-time
panic attacks, may represent depression rather than an anxiety disorder. ‘I can
often find no proper differences between the sadness and the anxiety of the
melancholic’, wrote Lewis in 1934.27 Major depressive disorder ‘without mood
symptoms’, or a masked depression, is a recognised, though not fashionable,
clinical state. Severe dysphoria tends not to be able to be hidden all the time, and
the relative’s history is often diagnostically pertinent. Differentiating mood and
fatigue in the physically frail is difficult. The will to achieve a task is retained in
the fatigued, though they don’t possess the energy to accomplish the goal. ‘I want
to, but I can’t’ is different from ‘I don’t want to, and I won’t’. ‘Vital exhaustion’ is
that state of extreme physical, and indeed mental, fatigue caused by actual or
impending physical ill health.28 Originally described as a precursor symptom to
myocardial infarction, terminal malignancy eventually creates a similar state.
Sedative medications can induce depressed and unresponsive affect.
Deteriorating renal and hepatic functioning may induce toxicity of these
and other previously tolerated medications. The psychomotor retardation of
drug-induced parkinsonism mimics depression. Hypoactive delirium is eas-
ily misdiagnosed for MDD. Torporosed patients appear affectively flat and
unreactive. The vague mentation consequent upon the cognitive inattention
of AIDS and paraneoplastic syndromes may seem affective, as may the gentle
cognitive withdrawal of the dying as interest in the present is sacrificed and
remaining energy focused on important interpersonal relationships. Nausea is
an occasional depressive symptom, particularly in the elderly, and despondency
associated with nausea is invariable.
The most challenging clinical dilemma is that of determining whether depres-
sive disease is influencing those who have made a decision to decline active
treatment when all medical hope is not lost. ‘Giving up’ in the face of insur-
mountable illness induces great concern, even anger, in relatives. It may be a
depressive symptom. Alternatively it may be a sensible and responsible decision
based on the reality of the clinical situation. If so it tends to be ‘affect neutral’
and neither patient nor family wears the gloom or doom of depressed persons.
A rational and analytical account of the decision-making is provided, and

rather than being hopeless, the patient has plans and expectations for the next
and terminal phase of their illness. The ‘giving up–given up’ concept,29 ‘learned
helplessness’, abulia and apathy are distinctly different from the constructive and
creative ‘giving up’. Resignation in advanced malignancy is not pathological if it
is based on a realistic appraisal of the future.
Demoralisation is a concept, recently championed by Kissane,30 of particu-
lar relevance to palliative care patients. Demoralisation is a form of existential
despair. The demoralised patient expresses non-specific dysphoria, such as
distress, irritability, guilt or regret, and a growing sense of disheartenment. Loss
of purpose and meaning can lead to helplessness, hopelessness, worthlessness
and an impatient desire to die or hasten death.30 Clinicians can perceive the
demoralised to be contemplating ‘rational’ suicide. Up to 8% experience severe
demoralisation, which interferes with competency to make informed and auton-
omous choice, and may coexist with or be a harbinger of clinical depression.
Change in morale spans a spectrum of mental attitudes from disheartenment
(mild loss of confidence), through despondency (starting to give up) and despair
(losing hope) to demoralisation (having given up). Historical terms such as
spiritual torpor, mopishness and acedia describe similar states of pointlessness
and a non-caring attitude to living. The philosopher Kierkegaard describing the
greatest despair of all stated that ‘when death is the greatest danger, we hope for
life; but when we learn to know even greater danger, we hope for death. When the
danger is so great that death becomes the hope, then despair is the hopelessness
of not even being able to die’.31 Clinically it is possible to differentiate demoralisa-
tion and depression.32 Demoralised patients, while feeling hopeless about their
future, feel immediately content with their present. The core features of depres-
sion are anhedonia, the loss of both anticipatory and consummatory pleasure,
and the loss of interest in life’s activities. The demoralised feel no anticipatory
pleasure, and are trapped and helpless. Still interactive with their environment,
they are unable to conceive an escape from their distress except by death.30
Whether demoralisation is a form of ‘subthreshold’ depression, an adjustment
disorder, a form of reactive dysthymia, or a separate diagnosis is uncertain.
Psychotherapeutic and social interventions of a supportive, empathic and
reality-focused style may be of benefit rediscovering a meaning for the remainder
of life.
DEPRESSION, SUICIDE AND DESIRE TO HASTEN DEATH

Depression is a factor in at least 50% of all suicides. More women than men
attempt suicide but because of choice of method, men are more likely to suc-
ceed. The peak incidences of completed suicide in the general population occur
during adolescence and, for males, elderly age. The frequency of suicide in the
DEPRESSION 103
cancer population is about twice that in the general population,33 with the high-
est risk in the months after diagnosis.34 Suicide is the cause of death in less than
1% of individuals with cancer.35 The risk decreases with survival time and is
very low in the terminal phase.36 Depression, uncontrolled pain, loss of control
(helplessness) and advanced disease (exhaustion) are considered indicators of
vulnerability to suicide in cancer patients.19,37 Examination of coroners’ files on
suicides in elderly males showed that 20% had cancer identified at autopsy or
had undergone treatment for cancer in the last year.38 Of particular pertinence
to the chronically physically ill, and not incorporated in suicide statistics, is
neglect of personal care, non-compliance and inattention to the necessary
care required by the disease. This carelessness may result in premature death.
Depression and hopelessness are independent risk factors for suicide. At high
levels of depression, the association with hopelessness is more dangerous, and
suicidality increases markedly.39 Depressive illness is potentially a fatal illness,
particularly if associated with hopelessness and existential anxieties. Hopes are
challenged by illnesses. Up to 45% of the dying struggle to maintain hope.40 It is
perhaps surprising in the presence of a poor prognosis, debilitating and fatal ill-
ness, fading hope and a depression prevalence of 5–15%, that completed suicide
is rare in cancer patients.
Suicidal thoughts occur in as many as 45% of terminally ill patients, though
these are usually fleeting and often associated with feelings of loss of control and
anxiety about the future.41 Such thoughts provide a fantasised escape, a finality,
from the current predicament. Contemplating a hypothetical exit plan of hasten-
ing death, the most common explanation for such thoughts, enhances the ability
to tolerate the present and provides an imagined sense of control and autonomy.35
The will to live fluctuates substantially over hours and days in the terminal phase
of life,42 often in unison with jags of distress or in conjunction with a realistic
sense of imminent death.35 Overall 17% of cancer patients in a palliative care unit
may have high desire for hastened death, this percentage being much lower in
community patients, suggesting that the intensity of these thoughts vary with the
trajectory, and the complications, of the disease.35 The desire for an early death
is reported in 1.4%, 8.5% and 23% of terminally ill patients.42–44 Depression was
diagnosed in 17.6%, 58% and 100% of these patients.42–44 In cancer patients with
major depression (12.8% of the cohort), 51.4% expressed suicidal ideation.45
Poor functional status and the severity of depression are significant risk factors
for suicidal ideation. Pain is not an influence.46 Depression and hopelessness
are the strongest predictors of desire for death.47 The existential state of mind
of the patient may reinforce the death-seeking ideation. The demoralisation
syndrome may progress to a desire to die or suicide.29,31 Treatment of depression
can diminish desire for death. A study of depressed geriatric patients’ preference
for life-sustaining therapy found that 25% showed an increased desire for such
therapy after treatment of their depression.48 This was particularly apparent in

several of the most severely depressed patients. The desire to hasten death, how-
ever, is not necessarily synonymous with a request to hasten death.
Requests by patients to hasten death are relatively rare in palliative care prac-
tice. They are possibly commoner in other areas of medicine such as neurology,
geriatrics and psychiatry. In the USA, 12% of physicians received one or more
explicit requests in the previous year, and in a terminal care setting 7% of patients
had asked.49,50 In view of the frequency of the desire and the numbers of patients
attended, it does appear that a sustained wish to die before nature determines is
rather uncommon, unless depressed. Requests by relatives, often spontaneously
and indirectly, are probably more frequent. The associations between depression
and suicide, and depression and euthanasia requests, are evident. One must ask
why so few patients commit suicide, and anecdotally they do not seem to be the
same cohort of patients as those who discuss euthanasia.51 Suicide is different
from asking to be killed. They are differing expressions of an individual’s control
over life and destiny.
MANAGEMENT
A correct diagnosis of major depression allows one of the most confident estima-
tions of response to treatment known to medicine. From the clinical perspective
a crucial decision is whether or not to introduce biological interventions. With
the emerging trend of the overprescription of antidepressant medication, for
these medications are tolerable and cheap (in comparison to psychotherapy),
the temptation is to diagnose positively in the ‘grey’ or marginal cases. However
medications have both physiological and psychological adverse effects and they
do not work in mild and reactive depressive syndromes.
The initial clinical task is to ensure the patient is safe, in a secure environ-
ment with careful ongoing monitoring. Suicidal ideation is an intensely personal
matter. Yet those harbouring such thoughts may be relieved that someone both-
ers to enquire about their intent, plan and access to means. Such questioning
is unlikely to prompt the patient to consider suicide, however it is advisable to
introduce the topic gently. For example, ‘have you thought you may be better off
dead?’ In the terminally ill, attending to associated uncomfortable symptoms of
their primary illness, such as pain, is critical. Adequate analgesia alone improves
well-being if not mood. Nausea is a most distressing symptom and creates
despair and desperation. For those previously physically active and energetic,
the fatigue of cancer may seem intolerable. Establishing a therapeutic alliance,
initiated by an empathic and sensitive assessment interview, encourages suffi-
cient trust to commence discussion about the required treatment modalities and
options. A psychological intervention is mandatory, whereas physical treatment
interventions should be reserved for moderate and severe depression. Initially
DEPRESSION 105
psycho-education about depressive disorders is necessary, and indeed this proc-

ess is really the introduction of psychotherapy.
Psychotherapy
Psychotherapeutic interventions need to be matched to the condition and to the
individual. In mild depression and reactive dysthymia, merely acquiring the his-
tory may be sufficient. The clarification of stressors, the offering of empathy and
understanding may allow the patient to forthwith regain coping and competency.
Information about the condition and its expected prognosis may be reassuring.
The anxiety of ‘going crazy’ and ‘out of control’ is a fundamental fear for eve-
ryone. Consultation–liaison psychiatrists spend much of their time diagnosing
‘sanity’ and ‘sadness’ in the physically ill.
Physical touch is soothing both for body and mind. Nursing staff can
easily capitalise on this and very rapidly establish a (psycho)therapeutic rela-
tionship. Relaxation therapies and many complementary treatments involve
distraction, physical loosening, and reinforcement of simple task competency.
‘Psychologising’ personal problems is very much a Western concept. Most peo-
ple of the world portray distress in a physical modality, and it responds well to
somatic interventions, albeit transiently. Psychotherapy has acquired a reputa-
tion as therapy provided only by specifically trained experts. For the physically
frail, such talking therapies are often neither feasible nor effective. Potentially
the most potent psychotherapist for the dying is the attending nurse, for she has
jurisdiction over the patient’s physicality. Her reassurances and esteem building
can prove the foundation upon which the depression lifts.
Patients in the ‘grey zone’, in whom some minor and variable physiological
symptoms of depression may be present, may require a more formalised psy-
chotherapeutic approach. Short-term supportive psychotherapy (perhaps 4–10
sessions), based on a crisis intervention model, should be provided. The aim
of therapy is to enhance morale and self-esteem while decreasing distress and
improving coping methods or strategies.52 Reinforcing self-worth by emphasis-
ing past strengths and previous successful ways of coping, correcting negative
misconceptions and cognitions, addressing current interpersonal conflicts and
supporting adjustment to the limitations imposed by the disorder are some of
the core tasks of therapy. Poor social supports, social disconnection and isolation
compound coping difficulties. Involving family is often advisable and certainly
they need information and support. Cognitive–behavioural therapy (CBT),
interpersonal therapy (IPT), analytic psychotherapy and a vast array of talking
therapies all have clinical advocates. Cognitive therapies involving reframing and
restructuring of negative thought patterns can help shift passive helplessness to
a more active coping style. The necessary basic ingredients of all such therapies
include empathy, interest and support over a time-limited period. Termination of
therapy is a component of the treatment, and this is as important in the dying as

it is for all. Cathartic psychotherapies are popular. They seem comprehensible to
many, for ‘getting things off one’s chest’ appeals, they don’t demand any internal
change or accommodation, therefore the distress soon recurs. Impending death
can serve as a powerful psychological tonic. Rapid and meaningful resolution of
personal and family dynamics can occur. There are studies suggesting that psy-
chosocial interventions result in longer survival, perhaps because of improved
adherence to medical care. However there is no literature on the effectiveness of
psychotherapy on depressive, rather than distressing, symptoms.5,53
Melancholic patients also require good supportive psychotherapy. The focus
needs to be pragmatic and educational about the disease ‘depression’, and com-
pliance with medication. Procrastination needs to be advocated, for ill persons
should delay in making major life-determining decisions, until well. Guidance
and distinct advice for these patients may be required in the interim until they
recover sufficiently to resume autonomous functioning. Medical paternalism can
be both benign and therapeutic.
Pharmacotherapy
The major clinical decisions with respect to choosing an antidepressant are those
of the symptom profile, adverse reactions and the required onset of action. There
is little if any efficacy difference across the range of available antidepressant
medications. There is a hint that TCAs, if tolerable, may be more effective in
treating depressions in the context of a life-threatening illness.54 Antidepressant
medications treat MDD successfully in 65% of cases.3 SSRI, TCA and MAOI
antidepressants all have a 60–70% response rate in the otherwise physically
well. However, the response rate in organic depressions is closer to 40%.55
Psychostimulant response rates are around 50%. Antidepressants are effective
for the treatment of depression in palliative care, their superiority over placebo
increasing with continuing use.54 The numbers needed to treat (NNT) decreased
from 9 at 6–8 weeks to 5 at 9–18 weeks, suggesting a useful clinical effect of
antidepressants in this population.54 Increasingly, it is recognised that the type
of affective symptom suggests the appropriate and effective medication. Parker’s
model of symptom profile determining antidepressant choice is useful.7 A sero-
tonergic medication should be used for anxious depression, a noradrenergic
antidepressant for retarded or melancholic depression, and if psychosis is a fea-
ture then an antipsychotic medication should be added.7 In those with previous
effective antidepressant use it is sensible to recommence this particular medicine.
The choice of medication in the terminally ill is influenced by comordid
conditions and adverse reaction profile. Antidepressant medication may have
analgesic actions (see Chapter 6), interact with analgesia (e.g. SSRI and codeine)
and assist sleep, and anticholinergic side effects may assist continence. They may
DEPRESSION 107
aggravate an already dry mouth, cause nausea and diarrhoea, blurred vision,
and induce bladder spasm, a serotonin syndrome or delirium. Physically ill
patients are particularly prone to, and troubled by, medication adverse reac-
tions. The adverse effects of medications are not only physiological. Introducing
psychotropic medication, particularly if the diagnosis is uncertain, tends to psy-
chologically undermine already strained coping strategies. The implicit message
of prescribing is ‘you can’t recover with your own resources, you need chemi-
cal help’. Actually, this is incorrect for most affective disorders. Antidepressant
medications merely enhance the rate of recovery, for eventually, at indeterminate
time (from 6 months to decades), depressions tend to spontaneously remit.
Many patients perceive the introduction of antidepressants as a personal failure.
Adding to the burden of dis-ease associated with their primary disorder, medica-
tion adverse reactions are likely to dissuade compliance. Drug–drug interactions
may occur as therapies change. Tamoxifen-associated reduction of TCA levels
in blood has been reported, as has SSRIs decreasing the anti-cancer effective of
tamoxifen.56
There are undoubted barriers to the prescribing of antidepressant medications
in palliative care settings. These include underrecognition of depression, lack of
clinical knowledge and prescriber confidence, the stigma of psychiatric illness,
the focus on other symptoms, the fear of compounding the patient’s distress, and
a sense of therapeutic nihilism in the dying.41 Only one-third of 150 clinically
depressed cancer patients actually were prescribed antidepressant medications in
a recent Scottish study,57 and 32% (mostly an SSRI) in another.44 A 30% increase
in psychotropic prescribing over a 10-year period has been documented.58 While
these figures are an improvement on earlier studies they still suggest undertreat-
ment. Educating oncologists to prescribe antidepressants (fluoxetine) utilising
a brief assessment tool and a simple treatment algorithm was shown to result in
uniform improvement in a group of their patients.59 Educating non-psychiatrist
colleagues is obviously the most likely successful strategy to improve the rec-
ognition and appropriate treatment of depression. Clinicians should have a low
threshold for initiating treatment.41 Because of the enhanced propensity of the
medically ill to experience adverse reactions of psychotropic medications, and a
tendency for response to occur at lower doses, antidepressants should be ‘started
low and go slow’.
The duration of expected life in the terminally ill is a very relevant influence
upon antidepressant choice. The rate of therapeutic onset of antidepressant
medications has long been of clinical concern and dubious industry claims. It
is generally accepted that there is a lag between the necessary therapeutic dose
and clinical response of 1–2 weeks, and for some patients 4–6 weeks irrespec-
tive of the particular compound. Indeed in the palliative care population this
may be even longer.54 Yet response can occur within days for some.60 Prior
to improvement of mood in medication-responsive patients, a transient and

potentially dangerous jag of enhanced anxiety may occur. This is probably a
mild serotonin syndrome induced by the medication. It settles over 24–48 hours,
and its intensity is relieved by benzodiazepines. Florid serotonin syndromes may
rarely occur with medications and combinations that enhance serotonin activity.
Within hours the patient may develop agitation, a hyperaroused state, myo-
clonus, hyperreflexia, diaphoresis and disturbance of consciousness. Normality
returns usually within 72 hours, with cessation of the medication and supportive
care. Conventional clinical opinion is that a therapeutic trial generally takes
4–6 weeks. For the terminally ill this lag may preclude the use of conventional
antidepressants, hence the role for psychostimulants.
The effectiveness of combined psychological–pharmacological therapy in
physically well adults is impressive, in the vicinity of 70–80%. Effectiveness of
antidepressants has been shown in depressed cancer patients.54 There is insuf-
ficient evidence-based information in hospice and terminally ill patients to
confirm such good response rates. However, it would be surprising in view of
the knowledge that organic depressions are less responsive to treatment and
most terminally ill patients have relevant organic aetiological influences upon
their mood. TCAs in a cohort of medically ill patients (some of whom had
cancer) resulted in only a 40% response rate.55 Once initiated, antidepressants
in the terminally ill generally should be continued indefinitely. The exception to
this may be psychostimulants. A short 2–3-week pulse of this treatment can be
sufficient to lift a depression and initiate neurotransmitter recovery. However,
dose may require adjustment with the emergence of organ failure. Prophylactic
antidepressant introduced prior to high-dose interferon-alpha therapy has been
shown to prevent depression.61
Selective serotonin reuptake inhibitors (SSRIs)

Fluoxetine, available since the late 1980s, revolutionalised antidepressant
prescribing. It is remarkably tolerable and safe. The gastrointestional adverse
reactions (nausea, anorexia, diarrhoea) occur in less than 10%, and insomnia,
headache and drowsiness even less frequently. Nausea tends to emerge early and
abate quickly, though if this does not happen after several days (and anti-emetics
rarely help), cessation needs to be considered. Initial anxiety enhancement is to
be anticipated and in the forewarned patient is rarely problematic. The concerns
regarding an increase of suicidality have been overemphasised. All effective anti-
depressants lift mood and enhance energy and purpose, and suicidal risk can be
anticipated to also increase transiently. Comparing this minute risk to the rate of
suicide in untreated depression (about 50% attempt suicide) needs to be incor-
porated into the risk–benefit decision-making of the clinician. The serotonergic
syndrome is rare, unless combined with another serotonin-acting compound
DEPRESSION 109
(including St John’s wort). The sexual adverse reactions are of concern, even in
a terminally ill population, as is the risk of inappropriate antidiuretic hormone
secretion. SSRIs are as effective as TCAs. Fluoxetine is available in tablet and cap-
sule forms. The contents of the capsules can be dissolved in water and aliquots of
smaller doses can be measured out, if the liquid preparation is unavailable. This
may be very helpful in those having difficulties swallowing. An advantage as well
as a disadvantage of fluoxetine and its active metabolite is the long half-life of 7–9
days (though metabolites may last in the system for weeks). This allows infre-
quent dosing regimes (and better compliance), but if intolerable it creates lengthy
adverse effects. Drug interactions are problematic with fluoxetine. All so-called
antidepressants are effective anxiolytic medications, perhaps more effective than
they are antidepressants. More recently developed SSRIs, particularly citalopram,
escitalopram and sertraline, are preferable for use in the physically ill as they are
slightly better tolerated and virtually free of drug interactions.
Tricyclic antidepressants (TCAs)

The most commonly used TCAs are the tertiary amines (amitriptyline, doxepin)
and the secondary amines (nortriptyline, desipramine). Seemingly because
of its use in the management of neuropathic pain, amitriptyline is a frequent
choice. It is viciously toxic in the medically frail. The adverse reactions include
anticholinergic effects (dry mouth, constipation, tachycardia, postural hypoten-
sion, blurred vision, urinary retention and delirium), arrhythmias, orthostatic
hypotension and sedation. It increases the risks of falls threefold. In medically
ill patients (including some cancer patients), 32% had to withdraw from the
medication because of adverse reactions (delirium 16%, urinary retention 4%).55
Amitriptyline’s active ingredient is nortriptyline, which is a very much better
tolerated medicine. Nortriptyline should be commenced at 5–10 mg nocte and
slowly titrated upwards until a reasonable sleep is achieved, without daytime
sedation. This is usually about the therapeutic dose. In physically healthy adults
the therapeutic dose is 75–125 mg nocte. Particularly in debilitated patients,
low dosage regimes tend to be effective. Serum levels of nortriptyline, unlike
the other tricyclics, are an accurate indicator of therapeutic and toxic ranges.
Drug–drug interactions, particularly with antihypertensive regimes and seda-
tives, should be monitored. TCAs can be administered as rectal suppositories if
the oral route is not possible. Parenteral forms have been used but are not easily
available.
Psychostimulants
Psychostimulant medication has a distinct role in palliative care. Used in North
America to counteract the sedation associated with high-dose opioid analgesia
and augment opioid analgesic regimes,62 they also have an important place in the
management of depression associated with advanced physical illness. Anxiety

can also be improved by psychostimulants, a phenomenon (with smoking)
known as Nesbitt’s paradox. Clinical responses to stimulant medications are
devious. In normal subjects initial drowsiness occurred in 50–65%,63 and this
is also recognised with caffeine. A beneficial and alerting response to caffeine,
which occurs in about one-third of users (as does sedation), can be a clinical clue
that a response to a stimulant may eventuate.64 Six cups of coffee (600 mg caf-
feine) is roughly equivalent to 5 mg amphetamine.65 Alertness to stimulants only
occurs in 33–50%. The effectiveness of stimulants is greatest when the subject is
sleepy (or perhaps physically frail). The onset of action of psychostimulants is
rapid, usually within 24–48 hours. Obviously this is of tremendous advantage in
the terminally ill. There appear to be no established differing clinical effects of
dexamphetamine and methylphenidate. Pemoline has been withdrawn for safety
reasons (cardiac malformation risks). Modafinil is emerging as the psychostimu-
lant of choice. There are no robust clinical trials to support the effectiveness of
psychostimulants in depressive disorders, but anecdotally it seems as if it may be
in the vicinity of about 50%, significantly less than with conventional antidepres-
sants. However, in the physically ill psychostimulants may be at least as effective
as conventional antidepressants, if not more so. In cancer patients, 83–96%
showed some improvement within 48 hours of commencement, and only
10–11% discontinued due to adverse reactions.66,67 Doses of methylphenidate up
to 20–30 mg/day are usually adequate. For psychiatric indications such as atten-
tion deficit hyperactivity disorder (ADHD), methylphenidate 1 mg/kg may be
used; however, this appears not to be necessary when used as an antidepressant.
They are generally well tolerated in advanced cancer patients.67 Headache, agita-
tion and restlessness may occur and delirium is a documented risk (particularly
in demented individuals), though such medications have been advocated for
hypoactive deliria. Cardiac arrhythmia is a relative contraindication, as resting
pulse rate is slightly increased, though psychostimulants are safer than tricyclics
for the heart. Only with chronic use (at >50 mg amphetamine/day), very high
dosage (100–300 mg amphetamine/day) and in schizophrenic patients is there
a risk of paranoid psychosis. Doctors tend to overestimate the adverse-effects of
psychostimulants, probably because of limited prescribing experience. Because
of their activating action, psychostimulants should be administered early in the
morning. They may additionally improve energy and appetite.68 In contrast to
their use as an appetite suppressant in the young diet-conscious female, in the
physically ill they tend to motivate appetite. While diversion needs to be consid-
ered, the risks of dependence and addiction in the physically ill are negligible.
The duration of use needs to be determined by trial and error. Many organic
depressions respond with a pulse of 2–3 weeks of psychostimulant, some require
an ongoing regime. Dose escalation/tolerance appears not to be a problem,
DEPRESSION 111
except in those with substance abuse histories. In persons with expected lon-
gevity, commencing a conventional SSRI concurrently is safe, and when the
antidepressant therapeutic activity kicks in, the stimulant can be ceased. There
are suggestions that efficacy of psychostimulants may fade in the last days of
life,69 as the dopamine and noradrenaline levels are too depleted to be able to be
released. Modafinil may assume the mantle as the preferred psychostimulant for
it appears to have no reported abuse potential.
Other antidepressant medications

MAOIs tend not to be used because of interaction risks. Moclobemide, particu-
larly if effective in a prior depressive episode, may be used, for interactions are
unlikely. Trazodone is a useful hypnotic but has unpredictable antidepressant
efficacy. Venlafaxine is a serotonin–noradrenaline reuptake inhibitor (SNRI).
At doses less than 225 mg/day it is a conventional SSRI, at higher doses it is
dual acting. It may have a particular role in neuropathic pain. Mirtazapine is a
noradrenaline and specific serotonin antagonist (NaSSA). It is fast acting, virtu-
ally devoid of anticholinergic adverse reactions, improves sleep disturbance, is an
appetite stimulant, and an anti-emetic. It is used increasingly as a co-analgesic in
chronic pain, and may assume a role as an alternative to the TCAs in this setting.
For the above reasons mirtazapine is increasingly widely used in palliative medi-
cine.54 There is a promising literature, particularly relevant to palliative medicine,
supporting the rapid treatment of depressive symptoms with ketamine.70 The
response may not be lasting but it may be a safe and effective option.70
Other treatments
Electroconvulsive therapy (ECT)
The safest and most effective of the antidepressant therapies, ECT, is rarely a
possibility for the severely medically ill. The major risks of ECT are those of the
general anaesthetic. However, the treatment option should not be dismissed for
it can be a magical intervention for severe suicidal and psychotic depressions.
Repetitive transcranial magnetic stimulation (rTMS)

This treatment method delivers magnetic pulses to the cortex, which induces
an electric current in the underlying tissue. It is non-invasive, it is possible to
stimulate relatively small brain volumes, and it is regarded as being safe and
without enduring adverse effects.71 Headache is the commonest complaint after
rTMS. As yet there is mixed efficacy data for the treatment of depression, but
sufficient for it to be approved in the USA. It is being researched for use in anxi-
ety states, PTSD, tinnitus, migraine and acute pain. Repetitive TMS may emerge
as a tolerable and effective treatment of depression in advanced cancer patients.
Seizures are the primary safety concern. At higher doses therapeutic seizures
can be induced (Magnetic Seizure Therapy, MST), potentially providing a safer

form of ECT.71
Phototherapy
Established as an effective treatment of seasonal affective disorder, the efficacy of
bright light therapy for non-seasonal depression is less established. It has been
shown to be a useful adjunctive treatment to antidepressant medications. It is
inexpensive, the ‘light’ box can be set up in the home, and adverse effects are
unusual.72 Three terminally ill patients, without seasonal affective disorder, were
reported to respond within days to exposure to bright wide-spectrum light.72
Complementary and alternative medicines (CAM)

Approximately 40% of US adults use CAM therapies and perhaps half of those
who use these therapies are doing so for mental health indications, most com-
monly depression.73 The majority are also receiving conventional healthcare, yet
only a small minority reveal this to their mental health provider. Rarely are these
therapies used as monotherapy, and good methodological studies are lacking.
S-adenosyl-L-methionine has the most promising support as an antidepressant,
omega-3 fatty acids and folate may be reasonable low-risk augmentation strat-
egies, and St John’s wort (hypericum) may be effective in mild depressions.73
Adverse effects are minimal; however, St John’s wort induces the cytochrome
P450 3A4 system thus potentially reducing the therapeutic effect of immunosup-
pressant, antiretrovirals, anticoagulants and antineoplastic agents, and inducing
serotonin toxicity. Labelled as ‘natural’ and perceived as being devoid of stigma,
these therapies, however, can be expensive and an inadequate response may
result in delaying other efficacious treatment of a condition with possible lethal
symptoms.
Proving consistent effectiveness of acupuncture for depression has been dif-
ficult. Exercise certainly enhances general mental well-being, but at the modest
levels possible for terminally ill persons, though it may assist fatigue, the avail-
able ‘dose’ may be inadequate. Alternative forms of psychotherapy, not currently
considered conventional practice, such as mindfulness-based cognitive therapy,
problem-solving therapy and well-being therapy may be promising in mild
mood dysfunction but have yet to be adequately studied.73
The use and effectiveness of traditional herbal medicines in many countries
has not been ascertained scientifically. They have powerful culturally supported
placebo action and some may well have additional antidepressant efficacy. It is
unwise to dismiss their possible biological potency. In developed countries the
popularity of CAMs for mental health is increasing in parallel with their appeal
in cancer care. When mood adversely affects quality of life it is clinically prudent
to enquire as to their possible use – information only rarely volunteered.
DEPRESSION 113
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Psychiatry. 2010; 71: 669–81.
CHAPTER 9
Delirium
When body is ill, soul goes awry often: it raves and utters foolishness, and
sometimes lethargy weighs it down to deep and endless sleep.
Lucretius (c. 99–c. 55 BC)1
Delirium is a common, if not inevitable, syndrome occurring during the final

24–48 hours of life. Prevalence figures in the dying of up to 88% are quoted.2
Delirium is a harbinger of death. It is underrecognised, undertreated and fre-
quently mistreated.3 To suffer delirium is frightening and distressing to both
patient and staff.4 The symptoms of delirium may be ameliorated and palliated
even though its occurrence may be indicative of irreversible organ failure.
CONCEPTUALISING DELIRIUM
The term ‘consciousness’ in the DSM and ICD-10 diagnostic criteria for delirium
(see Box 9.1) raises conceptual complexities, for it has differing medical and
philosophical meanings.5 The terms awareness, alertness, attention, arousal and
awakeness have been used to clarify the meaning of ‘consciousness’, though they
BOX 9.1 DSM-IV criteria for the diagnosis of delirium5
● Disturbance of consciousness (reduced clarity of environmental

awareness) with impaired ability to focus or shift attention.
● Change in cognition (memory impairment, disorientation, language
disturbances, perceptual disturbances).
● Disturbance evolves over a short period of time (hours/days) and
fluctuates during the course of the day.
● Evidence of a general medical condition judged to be aetiologically related
to the disturbance.
117
all remain difficult to independently define.6 Consciousness is an amalgam of

these separate but interconnected cerebral functions.
Impairment of consciousness is the primary and universal clinical change
occurring in acute brain disease. Delirium lies on the continuum between full
consciousness and deep coma. Consciousness is that state of an organism that
enables cognitive processes to occur.7 Delirium is best considered as primarily a
disorder of alertness. Alertness refers to a state of enhanced readiness to receive
and process information, and to respond.8 When alert, stimuli are processed
efficiently and responses initiated rapidly. To use a radio analogy, alertness
represents ‘volume’. To be alert, the brainstem needs to be functional. The
predominant neurotransmitter involved is acetylcholine. Alertness is the ‘key’
that activates awareness. Awareness is the content of consciousness, it is higher
mental functioning, and is dependent upon an intact cerebral cortex.9 In radio
terminology it is being ‘in tune’. Arousal, or physiological readiness, is a more
general term than alertness. It refers to an activated peripheral physiological state
as well as to forebrain cortical activation.7 High physiological arousal may or may
not be associated with high levels of alertness, whereas low arousal tends to be
associated with poor alertness. There is an obvious association between sleep and
delirium. One needs to be awake to be conscious, yet the vegetative patient is
‘awake but not aware’. The electroencephalogram (EEG) findings in delirium of
generalised slowing are dissimilar to sleep. Delirium is but one of the disorders
of consciousness. Dreaming, hypnosis, minimal conscious states and vegetative
states are caused by differing impairments of these functions. At the bedside
the level of alertness, or consciousness, can be crudely evaluated (see Box 9.2).
To the clinician the central concept is that of ‘attention’. Attention is ‘a control
process that enables the individual to select, from a number of alternatives, the
tasks he will perform or the stimulus he will process, and the cognitive strat-
egy he will adopt to carry out these operations’.10 Attention is the sentry gate
of consciousness.11 Alertness and awakeness are prerequisites for attention to
occur. The importance of attention is that it may be objectively measured at the
bedside. Inattention, distractability (the failure to select) and perseveration (the
inability to shift attention) are key, though secondary or indirect, indicators of
delirium. The pathological process of delirium is impaired alertness, and the
clinical barometer of alertness is attention.6
The fundamental function of the brain is inhibitory, not excitatory. Its func-
tion is to suppress and organise the vast array of internal and external sensory
stimuli (predominantly visual). If this processing and filtering is disrupted then
uncensored and chaotic cognitive, perceptual, affective and motor function-
ing result. Hughlings Jackson conceptualised nervous system functioning in
evolutionary terms.12 Upon damage to the CNS, dissolution of function occurs
and behaviour reverts to that of an earlier (and intact) stage of development.13
DELIRIUM 119
BOX 9.2 Bedside indicators of delirium
● Level of consciousness:
− full (alert, aware, attentive)
− hyperalert/vigilant
− hypoalert/drowsy
− stupor/unrousable
− coma.
● Impairment of attention, as clinically assessed by:
− disorientation in time (inaccuracy of greater than 1–2 hours)
− inability to recall examiner’s name after 2 minutes
− dysgraphic errors (‘please write your home address’): omitted,
reduplicated letters, misalignment, spelling, syntactical and dyslexic
errors, hesitancy to write
− inability to count down from 20 to 1
− multiples of 2 (2 × 2, 2 × 4, 2 × 8 . . . 2 × 128 = 256 is the usual normal
range)
− inability to recall three paired objects after 2 and 5 minutes.
A loss of structure in the nervous system results in a compensatory increase

of function of lower order structures. There is a reduction from the voluntary
to the automatic, and from the complex to the simple. Damage to the nervous
system ‘releases’ the inhibition over the remaining healthy tissue, and so-called
‘positive’ symptoms are expressed. Hence the diversity of symptoms. Damage
to evolutionarily early structures, such as the brainstem, leads to downstream
symptoms (impairment of awareness) and progressive biological withdrawal, a
shutting down of the system (delirium, coma).
THE SYNDROME
But for him it was his last afternoon as himself, an afternoon of nurses and
rumours; the provinces of his body revolted, the squares of his mind were
empty, silence invaded the suburbs, the current of his feelings failed; he
became his admirers.
WH Auden (1907–73)14
The acute onset of psychiatric symptoms in a person with compromised physi-

cal health is a necessary prerequisite for a diagnosis of delirium. There may be
subtle prodromal symptoms such as restlessness, anxiety, insomnia, nocturnal

muddledness and dreaming. The night nurse may the first to note these changes,
for by day normality returns. The symptoms of established delirium are protean.
Dysfunction of the brainstem results in consequential disorder in higher-level
structure and function. Though the primary impairment is that of alertness,
awareness is devastated because of this. All and every psychiatric and psycho-
logical symptom may occur. Thoughts and ideas lodged in memory are released,
perceptual clarity is lost, and emotions spill out. Anxiety and fear are prominent.
Impaired attention leads to disorientation (particularly to time). Retrieving
recent memories and registering new memories results in distortions of mem-
ory and confabulation in an attempt to make sense of the world and prevent
catastrophic reactions.7 Sophisticated language functions deteriorate. Writing,
a skill acquired relatively late in childhood and a symbolic representation of
symbols (of sounds or speech) is vulnerable to error. Incoherent mutterings
are common. Disorganised thinking, difficulties grasping one’s circumstances
and, literally, ‘confusion’ occur. Nominal aphasia is common, but not specific to
delirium. Frank persecutory delusions may arise. Reasoning is defective. Visual,
and less commonly olfactory, tactile and auditory illusions and hallucinations
are indicative of the difficulties with alerting. Visual hallucinations occur in
40–75%, particularly in drug withdrawal deliria. These are highly variable and
range from simple flashes of light to more discrete images. They tend to increase
in darkness or upon closure of the eyes.7 The majority of deliria are hypoactive
or mixed with respect to motoric function; hyperactive deliria are rarer, only 2%
of the cases in critical care units.15 Hypoactive deliria are more frequent in the
elderly and are associated with worse outcomes,15 suggesting motoric function
is an indicator of severity. The sleep–wake cycle may be disrupted, sometimes
reversed. Interpreting the content of psychotic symptoms in delirium is difficult.
As in dreaming, there tends to be a component of the ‘day’s residue’.
There is, at least in the early phases of delirium, a fluctuation of the presence
and intensity of symptoms. The clarity of the so-called lucid periods of delirium
has not been quantified. Sundowning refers to the propensity for the aggrava-
tion of delirious symptoms as darkness falls, related partially to the loss of visual
reminders but also to bodily temperature change.16 Variations (of alertness) may
be created by the inherent gamma or ‘40 Hz’ rhythm of the brain. These episodic
bursts of energy link the various regions of the brain in order to foster functional
integration and to format information.17 Alertness has a diurnal pattern, peak-
ing in the morning. In Jacksonian terms the damage inflicted by the delirious
insult results in regressive behaviour and primitive attempts to repair or heal. If,
however, the toxic insult persists then there is no prospect of regeneration. With
progression toward coma, fluctuations of mental status become less frequent
and briefer.
DELIRIUM 121
CLINICAL ASSESSMENT
The history of a recent change in mental status may be volunteered by the patient.
Relatives and carers may provide compelling information and often describe a
nocturnal onset of these changes.
At the bedside the key task is to evaluate alertness (see Box 9.2). Attention
serves as an indirect barometer of alertness and awakeness. Inattention can be
measured. An inability to direct, focus and sustain attention is usually apparent
in the process of acquiring a history. Many bedside tests of attention, such as
serial sevens, are not only excruciatingly difficult to explain to delirious persons,
but are genuinely difficult tasks for most. Tests of cognition need to be simple
and to extrapolate steeply in difficulty. Multiples of two is such a test involving an
assessment of attention, concentration, recall and arithmetic dexterity. Reversal
of the spelling of one’s name, or a five-lettered word, and counting down from 20
to 1 are alternatives, the latter being the simplest. Traditionally, disorientation has
been considered a relevant clinical sign of delirium. However orientation to time
of day is the only valid test of orientation: day, date, month and year are of little
relevance for watches or cell phones supply this information, supermarkets are
open every day of the week, and sport is played most days of the year. It is surpris-
ing how often patients muddle mornings and afternoons. Misidentification of
other people (usually mistaking the unfamiliar for the familiar) is a consequence
of poor attention to detail or compromised registration. Paramnesia, the distor-
tion rather than the loss of memory, is more typical than a global impairment
of recent memory.18 Many struggle to recall the examiner’s name, let alone three
paired objects after 2 minutes. Dysgraphia, while not specific for delirium, is
not only a reasonably sensitive diagnostic aid, it is an easy serial assessment of
clinical progress.19 Bedside testing of constructional abilities such as the clock-
face test, if impaired does not distinguish delirium and dementia. However, if
normal, it is reasonable to conclude that the patient is not delirious. Testing
cognitive functioning is invariably distressing for the patient.20 It is bewildering
to expose the deficits and may precipitate anxious and catastrophic reactions.
Tests of cognition are best if brief and benign, and really serve only to support
the clinician’s clinical impression. Alone they are not diagnostically specific
of delirium.
The lack of clarity in thinking, literally confusion, is difficult to quantify
and is not exclusive to delirium. The ‘content’ of consciousness, the symptoms
of the ‘final common neural pathway’, are broad and non-specific to delirium,
occurring in other psychotic, affective and anxiety states. Illusions, visual hallu-
cinations, delusions, fear and moodiness are ‘downstream’ symptoms, and while
deserving of management don’t need to be quantified. Psychomotor behaviour is
a gauge of the depth of consciousness impairment. The route to coma is that of
initial hyperactivity (particularly if the cause is drug related), then hypoactivity
(particularly if hepatic or metabolic in aetiology) and coma. Myoclonus can be

considered a subtle motor sign of delirium, as is carphology (purposeless over-
activity, picking at the bedclothes, groping movements). Brief and aggressive
episodes of catatonic excitement, while unusual and unfortunately unpredict-
able, are dangerous. The sickest lose the capacity to arouse with behavioural
activity as delirium deepens.
Diagnosing delirium is essentially that of a bedside clinical judgement.
Criteria for uniformity, predominantly for research purposes, may be useful
additions to clinical practice as screening and confirmatory tools. There is a
multiplicity of such scales, all with attractions and limitations. The MMSE (Mini
Mental State Examination) quantifies the impairments but doesn’t distinguish
delirium from dementia. The most useful tool is the Confusion Assessment
Method (CAM, see Box 9.3),21 though the Delirium Rating Scale and the
Memorial Delirium Assessment Scale have advocates. However, the utility of
such aids to diagnosis in the daily practice of palliative medicine are limited.
BOX 9.3 The Confusion Assessment Method (CAM)21
● Feature 1: acute onset and fluctuating course. This feature is usually

obtained from a family member or nurse and is shown by a positive
response to the following questions: Is there evidence of an acute change
in mental state from the patient’s baseline? Did the (abnormal) behaviour
fluctuate during the day – that is, tend to come and go, or increase or
decrease in severity?
● Feature 2: inattention. This feature is shown by a positive response to the
following question: Did the patient have difficulty focusing attention, for
example, being easily distractible, or having difficulty keeping track of what
was being said?
● Feature 3: disorganised thinking. This feature is shown by a positive
response to the following question: Was the patient’s thinking disorganised
or coherent, such as rambling or irrelevant conversation, with unclear or
illogical flow of ideas, or unpredictable switching from subject to subject?
● Feature 4: altered level of consciousness. This feature is shown by any
answer other than ‘alert’ to the following question: Overall, how could
you rate this patient’s level of consciousness? (Alert [normal], vigilant
[hyperalert], lethargic [drowsy, easily aroused], stupor [difficulty to arouse],
or coma [unrousable].)
The diagnosis of delirium by CAM requires the presence of Features 1 and 2

and either 3 or 4.
DELIRIUM 123
Many patients have insufficient energy or interest to comply. The Single Question
in Delirium (SQiD), which merely consists of asking a friend or family member,
‘do you think [name of patient] has been more confused lately?’, demonstrated
in a palliative care population acceptable sensitivity and specificity as well as
obvious ease of administration in this frail population.22
The physical signs of delirium vary to some extent upon aetiology. The pres-
ence of tachycardia, hypotension, flushing, sweating, diarrhoea, tremulousness,
myoclonus and asterixis may hint at causes. In the frail elderly a febrile response
to infection does not always occur. Reduced tissue turgor and mucosal dryness
suggest dehydration. Pupillary size and examination of the optic fundi (if clini-
cally possible) are unreliable signs in the dying patient. Primitive reflexes, focal
neurology and meningism are suggestive of cerebral involvement. Myoclonus is
a common generalised sign of nervous system toxicity.
DIFFERENTIAL DIAGNOSIS
Testy delirium or dull decrepitude.
WB Yeats (1865–1939)23
All and every mental status aberration is possible in delirium. In the physically
ill, delirium should be excluded as a diagnosis prior to formulating an alterna-
tive psychiatric diagnosis. Credence should be given to the clinical dictum to
‘assume delirium until proven otherwise’. Disturbance to consciousness does
not occur in dementia, depression or schizophrenia. The diurnal fluctuations of
mood in depressive disorders are of a consistent pattern rather than the rapidly
changing, incontinent mood of delirium. Hypoactive delirium is liable to be
mistaken for depression. Most persons with delirium also met the diagnostic
criteria for major depressive illness,24 the affective disruption being secondary
to the cerebral disorganisation and loss of control. The history of dementia is of
gradual onset, and the impairments of longer-term memory, abstract thinking
and higher cortical functions (aphasia, apraxia) are different. Demented patients
are alert. Delirium is 2–3 times more common in the demented, the symptoms
of delirium overshadowing those of dementia if these disorders coexist. Fluent
aphasic patients present a diagnostic challenge. They are more likely to produce
neologisms and paraphasias in speech, and do not have attentional difficulties.
The hallucinations of delirium are most commonly visual rather than the typical
auditory hallucinations of schizophrenia. The delusions of delirium, most often
paranoid in nature, tend to be more fragmented, less organised and more fleeting
than those of schizophrenia.
AETIOLOGY
In the terminally ill delirium is generally multidetermined (see Box 9.4). Intensive
investigation provides specific causes in only 50%.25 The absolute strength and
activity of the noxious agent(s) and the host’s vulnerability to such insult are the
critical influences.7 A ‘delirium cascade’ can be initiated in the vulnerable by a
minuscule toxic event. The interrelationship of precipitating and predisposing
factors determines the clinical state (see Table 9.1). If vulnerability at baseline is
low, patients may be resistant to delirium despite exposure to significant precipi-
tating stressors, but if vulnerability at baseline is high, delirium is likely to occur
with exposure to only minor precipitating factors.26 Environmental influences
may moderate these risks by muting the impact of the toxin and/or by strength-
ening the host. Individual differences in susceptibility to reacting with delirium
to any given cause have been demonstrated.7 Conceptualising delirium in terms
of a ‘threshold’ model, a well-established model for epilepsy, is useful in under-
standing the various risk factors. The ‘deliriant threshold’ for each individual is
unique.6 The risk factors are multiplicative rather than additive. Limited ‘brain
reserve’, as in the dementing or immature infant brain, enhances risks, as does
the severity of the physiological insult. The physiological insult that eventually
tips the patient into delirium may be in itself minor. Previous delirium increases
the risk more significantly than does age and pre-existing cognitive impairment,
suggesting a kindling effect.27 Delirium is a syndrome of universal susceptibility.
TABLE 9.1 Risk factors in delirium
Predisposing factors Precipitating factors

Older age, very young age Severe acute illness
Presence and severity of dementia Infection
Previous delirium Hyponatraemia
Functional dependence Hypercalcaemia
Immobility Hypoglycaemia
Dehydration Hypoxia
Alcoholism Renal failure
Severity of physical illness Hepatic failure
Genetics ? Medication (opioids, tricyclics)
Pain
Anaemia
Cerebrovascular disease
Cerebral trauma
Alcohol withdrawal
Raised intracranial pressure
Post-ictal state
DELIRIUM 125
BOX 9.4 Causes of delirium in advanced cancer
Direct CNS involvement

● Primary tumour
● Brain metastases
● Post-ictal/seizures (including non-convulsive status epilepticus)
● CNS infection.
Systemic
● Organ failure:
− hepatic encephalopathy
− renal failure/uraemia
− respiratory failure (pulmonary embolus, lymphangitis carcinomatosis,
pulmonary oedema)
− cardiac failure.
● Electrolyte imbalance:
− hypercalcaemia
− hyponatraemia (rapidly occurring).
● Treatment-induced:
− anticholinergic medications
− opioids
− corticosteroids
− chemotherapy
− radiotherapy
− antiviral medication
− anti-emetic medications.
● Haematological:
− anaemia
− disseminated intravascular coagulopathy.
● Infection.
● Nutritional:
− vitamin deficiency (Wernicke’s encephalopathy).
● Paraneoplastic syndromes (limbic encephalopathy).
Specific organic diseases don’t give rise to specific delirium symptomatology.

Iatrogenic causes are potentially reversible. Medications with anticholinergic
effects in excess of 0.83 ng/mL of atropine-equivalent, are implicated in 20–40%
of all deliria.28 Opioids such as codeine (0.11 ng/mL atropine-equivalents),
prednisolone (0.55 ng/mL atropine-equivalents) and, of course, antidepressants
(particularly tricyclics) may lower the deliriant threshold.28 The relationship of
delirium and opioids remains uncertain. Anecdotally, there does appear to be a

chronological association on occasions. In a prospective study of postoperative
patients, however, delirium was nine times commoner in those deemed to have
undertreated pain than those complying with opioids.29 Nicotine withdrawal is
usually countered if the patient is taking opioids. The not insignificant mortality
of delirium tremens (DT) should persuade the clinician to treat on suspicion.
Emergency treatment of DT with alcohol needs to be occasionally considered.
Even at a late stage, reversal may be possible in up to 50%, particularly if opioids
and dehydration are implicated.2
PREVALENCE
Delirium is age related, though the symptoms are not age specific. Prevalence
and incidence rates in cancer units have been reported as 45% and 42% respec-
tively.2 The incidence increases toward the approach of death. On admission to
a palliative care unit 28–42% were experiencing delirium, a rate which increased
to 88% before death.2 If the road to coma is steep, then delirium may be passed
through very rapidly. For most of those dying from cancer, the path to coma
and death visits delirium. The prevalence of subsyndromal delirium may be
substantial. One-third to two-thirds of deliria may be non-detected.30 Nursing
staff have been reported to have better detection rates than doctors, no doubt a
feature of the length of direct patient contact involved in nursing as compared
to the relative brevity of medical assessment.31
INVESTIGATIONS
Each medical investigation is associated with discomfort and/or risks. The
only definitive diagnostic investigation for delirium is the EEG, which is not
likely to be contemplated in the dying. A simple blood screen for blood count,
electrolytes, glucose and calcium may provide clinically useful information. If
infection is a possibility, urinalysis is warranted. The enthusiasm for investiga-
tion should be influenced by the stage of illness and the prospect of establishing
a potentially reversible cause. Minimising iatrogenic discomforts such as that
created by investigations requires sound clinical decision-making. The confine-
ment and the noise associated with MRI scanning, for example, may exclude this
as an investigation option for the acutely delirious patient. Delirious symptoms
can be amplified by such stressors. Clinical judgement, rather than laboratory
tests, should determine treatment decisions. There is in palliative medicine no
justification to investigate for medical curiosity alone.
DELIRIUM 127
MANAGEMENT
Christ, may I die at night with the semblance of my senses, like the full
moon that fails.
Robert Lowell (1917–77)32
The cardinal rules of management were formulated by medical writers of antiq-

uity and these remain applicable today.7 Diagnosis and management occur
concurrently. Delirium requires therapeutic intervention beyond the identifica-
tion of the syndrome and amelioration of the underlying cause. Box 9.5 lists the
tasks of management in sequential and concurrent order.
BOX 9.5 Principles of management
1 Prevention and prophylaxis

2 Creation of a safe environment
3 Treatment of the cause(s)
4 Palliation of medical symptoms
5 Environmental strategies
6 Psychological interventions
7 Pharmacological interventions
Prevention and prophylaxis

Education of staff to ensure prompt recognition of delirium and multicomponent
intervention strategies are effective measures reducing the duration and dimin-
ishing the severity.33,34 Whether these strategies are truly preventative or prevent
symptom escalation of subsyndromal delirium is uncertain.
The role of cytokines in delirium or, more particularly, the possibility that
somatostatin and insulin-like growth factor-I (IGF-I) may prevent their rise, has
resulted in them being postulated as potential neuroprotective agents against
delirium.35 Physical exercise is known to increase IGF-I uptake by the brain, thus
supporting the purported protective role of exercise in delirium and suggesting
an adaptive purpose of the hyperactivity of delirium.36
Prophylactic antipsychotic medication in patients at high risk, at least anec-
dotally, appears beneficial. Prophylactic haloperidol, given preoperatively and
continued postoperatively, has been shown to shorten the severity and duration
of delirium, but not its incidence.37 The administration of 10mg of olanzapine
preoperatively in elderly joint-replacement patients significantly reduces the
incidence of postoperative delirium.38 The preventative use of cholinesterase
inhibitors similarly has appeal.
Creation of a safe environment

Delirium is a medical emergency. The initial priority is to minimise the risk of
injury and harm to the patient, relatives, other patients and staff.39 The symp-
toms are most easily containable within the familiarity of the home. The force
of delusional ideation associated with delirium can provoke extraordinary
physical strength, even in the elderly. The delusions of delirium tend to be poorly
organised, transient, and readily influenced by environmental stimuli,7 and coun-
terprojective dialogue, while important, does not have the value it does in the
more systematised and sustained delusions of schizophrenia. Counterprojective
dialogue refers to the assumption of a neutral attitude, by neither agreeing nor
disagreeing with the patient’s ideation, yet empathising with the distress these
thoughts must be causing them. Two-thirds of delirious patients were reported to
have tried to, or had run away from hallucinatory images.40 Perceptual release of
visual imagery may be terrifying and dangerous. Organic psychoses are notori-
ously unpredictable, and the dangers may easily be underestimated.
Informed consent for urgent interventions is often not attainable, unless a
convenient lucid period presents. Emergency and life-saving interventions are
governed by common law doctrine. Treatment may be given without informed
consent if the treatment is such that medical colleagues would generally consider
it appropriate, and a reasonable person would want it.39 If the risk of injury to self
and others is recurrent and persistent, and/or medical investigations and pro-
cedures are necessary, then utilising compulsory committal law is advisable, at
least until the acute symptoms settle. Transferring such patients to a psychiatric
ward is not appropriate, and may be dangerous because of the primary medical
condition.39
Physical restraint, which requires at least five able-bodied staff members,
should only be used if unavoidable, and only for very brief periods. The physi-
cal restraint of a delirious patient tends to increase agitation and paranoia,39 and
has been shown to increase the risk of deep vein thromboses, pulmonary emboli
and cardiac arrhythmias.41 The use of bed rails should be avoided as they merely
increase the height of the potential fall without reducing the risk of the fall.
Placing the patient’s mattress on the floor is a safe, but admittedly undignified,
option to increase the level of physical safety. The removal of dangerous objects
and possible weapons (such as cutlery) is a necessary precaution.
Diffusing and calming techniques should be practised. A wandering patient
may be managed by collusion; that is, walking with the patient and generally
redirecting them. Confrontation, the invasion of the patient’s personal space and
‘eyeballing’ are best avoided, as they are provocative. The effects of calming prac-
tices are not easily quantified, but anecdote and opinion suggest they certainly
reduce behavioural escalation and violence in delirious persons.
DELIRIUM 129
Treatment of the cause(s)

Overall reversibility rates of delirium are determined predominantly on whether
or not the causes are amenable to medical intervention. After correction of the
cause, resolution of the mental state may take several days. Toward the last few
days of life, reversal is less likely, for disease burden is considerable. However,
some interventions even at a late stage may be very effective. Antibiotic treatment
of a minor infection, opioid rotation, and adequate analgesia are such examples.
Medication regimes with marked anticholinergic activity may be reversed by
procholinergic agents such as physostigmine and cholinesterase inhibitors.
Palliation of medical symptoms

Antipyretic medications and cooling are of effect in reducing fever, oxygen may
be helpful in hypoxic patients, and analgesia may ease discomfort. Even when the
aetiology cannot be reversed, interventions that partially ameliorate the causes
should decrease the intensity of the delirium, e.g. managing anaemia with blood
transfusions or erythropoietin, raised intracranial pressure with corticosteroids
and hypercalcaemia with bisphosphonates. In the short term, fluid intake is more
important than nutrition (though solid food is an efficient provider of hydra-
tion). A subcutaneous infusion of 1–2 L of fluid overnight may be an option to
hydrate, although lines may be extracted by the muddled patient. Nasogastric
feeding is not recommended as it is unpleasant and patients frequently wrench
such tubes out. Urinary retention may require urinary catheterisation, and
attending to constipation is an important consideration.
Environmental strategies
Therapeutic manipulations of the environment are underutilised interventions
and free from adverse effects.42 Noisy, unfamiliar and unwelcome perceptual
stimuli further compound the existing impairment of sensory filtering in the
reticular activating system (RAS) of delirious patients, thus amplifying deliri-
ous symptoms. A failing brain, like an ailing heart, benefits from the reduction
of its workload, hence the desirability to restrict, but possibly not deprive, the
sensory input. A moderate sensory balance and an unambiguous environment
are preferable to sensory overstimulation.39,42 Defective perceptual discrimina-
tion facilitates the occurrence of distortions and misinterpretations of sensory
stimuli in busy environments.7 Light is the preferable environment for delirium,
and certainly in those in whom visual misperceptions are common the room
should be well lit.20
The noise level should be below 45 dB during the day and less than 20 dB at
night.36 Limiting staff interactions with the patient, minimising staff changes
and restricting visitors are important. Constancy of staff may be difficult to
achieve, and the theoretical advantages of nursing patients in quiet side rooms
must be weighed against the risk of nursing neglect.42 The presence of personal
artefacts and objects may reduce the unfamiliarity of a hospice environment. A
later acrophase of high core body temperature is implicated in the sundowner
effect in Alzheimer’s patients.16 The room temperature should be kept between
21.1˚C and 23.8˚C.36 A bland and simple environment reduces the perceptual
load on the brain.
Psychological interventions
Psychological interventions are underutilised, yet are easy and anecdotally
effective.43 Nursing staff and supportive relatives are best placed to use such
strategies as simple and firm communication, taking advantage of any lucid
moments, and repetition of any information provided. Continual reassurance,
orientation, explanation and clarification result in some relief of fear and bewil-
derment, albeit transiently. Holding the patient’s hand is an effective means of
focusing their attention and providing reassurance.42 The inherent fear of the
loss of sanity is difficult to check, for delirium is indeed insanity. That this state
is nearly always temporary and interspersed with episodes of sanity should be
emphasised. The use of the patient’s name can be an important point of reference
for the confused patient. Speaking slowly and using careful and distinct diction
may help.42 Fostering the individual’s sense of control and competency, where
possible, is important.36 The simple opportunity to clean one’s own teeth helps
retain and regain a semblance of dignity and autonomy. The attendance and the
assistance of close relatives, while ideal, can be countertherapeutic if the relative
is anxious or frightened.36
Delirium, by its very nature, virtually precludes the conducting of counsel-
ling and psychotherapy, and it hinders the patient’s ability to participate and to
be involved in therapeutic decision-making. It destroys any meaningful com-
munication for much of the time. Abreactive and explorative techniques are
contraindicated.
Pharmacological interventions
Non-pharmacological treatments should not be abandoned with the introduc-
tion of medication, indeed they should be practised with renewed vigour, for
the patient is likely to be increasingly responsive. The decision to administer
drugs should not be influenced by the relative’s wishes, time constraints or com-
munication difficulties between medical and nursing staff, but by the patient’s
condition.36 The benefits and the risks of adding medication to an already
medically sick patient need to be considered carefully. Medications are more
likely to be prescribed for frenetic, hyperactive delirium patients, because the
disruption caused to others around them tends to demand intervention,40 and
non-pharmacological interventions may be impossible to practise because of
DELIRIUM 131
the patient’s gross inability to attend. The administered antipsychotic dose in the
management of delirium in patients with advanced cancer has been shown to be
influenced more by healthcare professional distress than by delirium symptom
frequency.44
The intent of pharmacological intervention should be to alleviate the deliri-
ous symptoms (by tranquillisation), and if this is unsuccessful, to achieve a
reasonable clinical outcome of minimising problem behaviour (by sedation).36
Antipsychotic medications (also termed neuroleptic or major tranquilliser)
calm, pacify, tranquillise or sooth by enhancing inhibition of sensory input. The
‘workload’ of the RAS is thus reduced, and the ensuing clinical consequence
is the containment of the symptoms of delirium including agitated behaviour,
psychosis and cognitive dysfunction, sometimes with the total amelioration
of symptoms.36 Antipsychotic medications are effective in both hyperactive
and hypoactive deliria.45 They generally improve cognition in both subtypes of
delirious patients.46 Sedative (or hypnotic) medications immobilise and induce
(deep) sleep by depressing the level of consciousness. They carry a risk of wors-
ening delirious symptoms at subhypnotic doses. Tranquillisation may need to
be complemented with sedation, or on rare occasions a person may need to be
chemically restrained by anaesthesia. Pharmacological antidotes may have a role
if the aetiology is that of excess anticholinergic activity.
Antipsychotic medication
The medication of first choice for delirium is an antipsychotic. The mechanism
of action of these medications in delirium is uncertain.47 Maximal dopaminer-
gic blockade occurs at relatively low doses and the rapidity of therapeutic onset
of these agents (within hours) would suggest that this is not the mechanism of
their action in delirium. Rebalancing the dopamine : acetylcholine ratio is a
more compelling mechanism of action. A solitary randomised medication trial
supports their use.48
There are particular forms of delirium in which antipsychotic medication
is not the treatment of first choice. The use of benzodiazepines and/or a brief
anticonvulsant regime is the treatment of choice for delirium tremens. Hepatic
encephalopathy may be aggravated by the introduction of medications metabo-
lised by the liver. AIDS and Lewy body dementia patients tend to be exquisitely
sensitive to the neurological adverse effects of antipsychotic medications, thus
benzodiazepines and cholinesterase inhibitors are the management options of
choice. Animal studies indicate that antipsychotic medications may slow recov-
ery after traumatic brain injury, which is commonly complicated by delirium.
The possibility of dangerous elongation of the QTc interval and the induction
of torsades de pointes with antipsychotic medications needs to be considered in
the benefit–risk equation.
Although chlorpromazine and haloperidol have similar efficacy, haloperidol

is favoured for its preferable adverse effect profile and versatility of adminis-
tration.48 Haloperidol has few or no anticholinergic adverse effects, minimal
cardiovascular effects, and its neurological adverse effects can be minimised
by choosing the parenteral route of administration, such as the subcutaneous
route.49,50 Originally marketed as a ‘stimulant antipsychotic’, haloperidol is not
sedating.47 The efficacy, tolerability and safety have been demonstrated even at
very high dose (see Box 9.6).49 The neurological adverse effects of haloperidol
peak at mid-range oral doses (5–20 mg). Administration of low dosage or high
dosage (preferably parenterally) over a period of less than one month avoids
the build up of the neurotoxic metabolite ‘reduced haloperidol’.49 In usual clini-
cal practice the required dosage is only a few milligrams though doses of up
to several hundred milligrams (intravenously) have been used with effect and
safety. In the UK most intensive care consultants use initial doses of 2.5–5 mg
intravenously.51 Doses of haloperidol are variable and hard to predict.51 In the
treatment of hyperactive deliria in cancer patients low daily doses of haloperidol
(mean 2.5 mg) were used in 61% of patients, intermediate dose (mean 15 mg) in
32% and high dose (mean 30 mg) in 7%.52 Haloperidol has suffered a mistaken
reputation as a sedative and neurotoxic drug. However, in experienced hands
it remains the antipsychotic of first choice. Droperidol is no longer considered
safe because of its propensity to prolongate the QTc interval more than many
other antipsychotics. Chlorpromazine is painful when injected, and the risk of
hypotension is significant. Levomepromazine, a potent phenothiazine, is used
particularly if its major adverse effect, sedation, is desired to settle the agitated
and restless patient.
The hypothesis that agitated, hyperactive deliria is a high dopamine state
(like schizophrenia), and hypoactive/mixed deliria are states with low/normal
dopamine with marked dopamine/cholinergic imbalance, is based on the dif-
ferential response to types of antipsychotic medications but is purely theoretical
and inferential.53 Haloperidol, which narrowly targets the D2 receptor, is sug-
gested for the former, whereas atypical antipsychotics, with a broader receptor
coverage, may be preferable in hypoactive deliria. Risperidone may be the most
frequently used atypical antipsychotic in delirium.54 There are also clinical trial
reports on the use of olanzapine, aripiprazole and quetiapine.55,56 Effectiveness in
delirium is comparable to haloperidol (70–80% response rate), however sedation
was a notable adverse effect, though extrapyramidal complications were less.
There are reports of these medications aggravating or precipitating delirium.57
This may be explained by the possibility of atypical antipsychotics selectively
increasing dopamine in the medial prefrontal cortex because of 5HT2A activ-
ity.53 Usefulness of these medications in the acute setting has been limited by
the unavailability of short-acting parenteral options. The consensus appears to
DELIRIUM 133
be that the efficacies of haloperidol and atypical antipsychotics are equivalent,

but that there may be fewer adverse effects with the latter.58 Clinical reports
suggest good response to the atypical antipsychotics, but ‘a solid evidence base
in palliative care is lacking’.59 The risk of cerebrovascular complications of these
medicines in this population is uncertain and questionable.60
BOX 9.6 Intravenous haloperidol regime for acute delirium (adapted from
Massachusetts General Hospital Guidelines)
● Initial dosage:
− mild symptoms: 1 mg
− moderate symptoms: 5 mg
− very severe symptoms: 10 mg.
● Repeat and double dosage in 20–40 minutes if no control.
● Repeat and double dosage each 20–40 minutes until clinical control
achieved.
● Await reappearance of symptoms and repeat last dosage.
● Introduce oral dosing.
● Phase out progressively as delirium clears.
Note:
● 80% require <2 mg/24 hours.
● Most settle within 1 hour.
● Maximum single dose: 20 mg.
● Maximum daily dose: 100 mg.
Sedative medication
Opium has been used since antiquity for its sedating effects, though tolerance to
this adverse effect develops rapidly. Benzodiazepines are now the sedative drug
of choice.7 The induction of sleep in delirium may be crucial for the exhausted
hyperactive patient in order to secure rest and safety. Benzodiazepines may
reduce agitation in delirium, but they may also worsen cognitive impairment
for they further lower consciousness and thereby aggravate delirium. To sedate,
the required dose must be rapidly reached. Because of its very short half-life
and speed of onset, midazolam is the benzodiazepine of choice. It is unlikely
that there are distinct sedative efficacy differences between the benzodiazepines,
and pharmacokinetic parameters should determine the choice. Their most clini-
cally useful role is to safely augment antipsychotic medication and induce sleep
and rest if required. The risk of a paradoxical behavioural response is small
and predominantly related to pre-illness characteristics.61 The failure to induce
disinhibited behaviour even in a high-risk population suggests this concern

is overstated.62 Respiratory depression and arrest may occur with intravenous
administration of benzodiazepines and needs to be considered as a risk. The
safety of benzodiazepines in the medically ill is remarkable, and the availability of
an antidote, flumazenil, is reassuring to the clinician, but rarely if ever necessary.
Anaesthesia
Deep sedation with respiratory support may rarely be required to control severe
hyperactive deliria. Propofol at low dosage (10–50 μg/kg/min) has been used to
anaesthetise these patients to enable treatment of the life threatening cause (such
as acute viral encephalitis). Dexmedetomidine, a selective alpha2-adrenergic
receptor agonist, a novel anaesthetic agent, has also been trialled in postoperative
delirium.63 Dexmedetomidine has the potential to allow a state of tranquillity and
analgesia, without sedation.
Antidote medication
Dopamine–acetylcholine imbalance is postulated to be the central lesion
in delirium. Acetylcholine decreases with age and is reduced in dementia.
Many medications have significant anticholinergic activity.33 Physostigmine
(0.5–2.0 mg IV) rapidly reverses symptoms of anticholinergic delirium. The use
of cholinesterase inhibitors in delirium in Lewy body dementia might also be
considered an antidote intervention.64
Other pharmacological interventions

Psychostimulants such as methylphenidate have been used in hypoactive
delirium to arouse and stimulate consciousness.65,66 The 5HT2 antagonist antide-
pressants mianserin and trazodone have been shown in open studies to rapidly
reduce non-cognitive symptoms of delirium at low dose, this being independent
of the mood-altering actions.67 The cholinesterase inhibitor, rivastigmine, has
been shown to aggravate the symptoms and outcome of delirium in a critical
care population.68 Other studies have been supportive.69
Outcome
Rapid and full recovery is the desired outcome. A delay of up to several weeks
in the ‘high risk’ persons, but a few days for most, is to be expected between
abolishing the cause and the recovery of senses. In frail cancer patients, 68%
were reported to have improved despite a 30-day mortality of 31%,25 and rates
of reversal of nearly 50% have been reported in such patients.2 The outcome will
depend upon the nature of the offending physiological stressor, the biological
vulnerabilities of the patient and moderating environmental factors. The belief
that full recovery generally occurred after delirium has been shown to be unlikely
DELIRIUM 135
to be correct, especially in an elderly population. Enduring cognitive deficits,

a subsequently lowered ‘deliriant threshold’ (hence the probability of future
episodes), psychiatric morbidity and death may result. Complete symptom
resolution was seen in only 52% of elderly hospitalised patients 12 months after
delirium, and prolonged memory impairment was common in these patients.70
Recollection of delirious episodes tends to be patchy (as would be expected with
fluctuating cognitive and memory symptoms). These memories are distressing
in 50%,4 and the delirium experience has been reported to induce PTSD. The
prevalence of accidental injury and suicide in delirium are not known. Mortality
rates in the delirious hospitalised elderly range from 22% to 76%, and over 80%
of those with terminal malignancy die delirious.2 Historically, delirium has
been considered the harbinger of death.7 In the palliative care patient popula-
tion it should not be assumed that full recovery will occur even if the causes are
reversible.
It is uncertain how effective interventions for delirium are. Clinically, there is
little doubt that significant palliation of symptoms is possible. In those cases in
terminal care where the causes can’t be reversed, and the symptoms are unable
to be contained with multicomponent interventions (including pharmacologi-
cal tranquillisation), deep sedation may be indicated (see Chapter 10). Dying
is difficult, dying crazy is more difficult. Such ‘bad’ deaths may be preventable.
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delirium. J Gerontol. 1993; 48: 162–6.
CHAPTER 10
Sleep, sedation and coma
When youth is wakeful and old age drowsy, death is nigh.
Ambroise Paré (1517–90)1
DISTURBANCES OF SLEEP
Sleep is a state of ‘suspended consciousness’, a temporary interruption of senso-
rimotor interaction with the environment. Clinically, the distinguishing feature
of sleep, in contrast to coma, is the ease with which the sleeping subject can be
roused to awareness of the external world. Normal sleep consists of two distinct
phases. Normal sleep architecture is a continuous cycle, lasting approximately
90 minutes, of non-rapid eye movement (NREM) sleep and rapid eye movement
(REM) sleep. The functions of sleep include rest and restoration, both physically
and mentally. Stages 3 and 4 of NREM sleep (slow wave sleep, SWS) reorganise,
update and repair the brain’s synthetic processing or programming. An increase
of immune activity also occurs during sleep.2
Total sleep time and time spent in SWS gradually decrease with age, and
fragmentation of the pattern becomes more pronounced. Sleep efficiency is not
proportional to the duration of sleep, and many elderly spend increased time in
bed for lesser reward. The very elderly, and the profoundly ill, rest and sleep for
longer periods, though the sleep doesn’t refresh. Frequent daytime micronaps
and a shorter night sleep are typical features. Clinically determining a patient’s
actual sleep is difficult. Lack of sleep tends to be overestimated by most (pseudo-
insomnia). A sleep diary and an interview with the bed partner and/or carer are
the necessary sleep assessment tools. Polysomnography is seldom indicated, nor
is it feasible. Affective disorder and chronic pain adversely affect sleep. Poor sleep
is a contributing factor lowering the pain threshold, thus in palliative medicine
sleep disorders merit serious attention.2 Acute pain interrupts stage 2, NREM
sleep, though how more chronic pain disrupts is less certain.3 Sleep efficiency
139
is reduced in chronic pain because of delayed sleep onset, frequent awakenings

and alpha-delta intrusions into NREM.4
Insomnia
Insomnia is a common complaint of the terminally ill. In the general population
difficulty getting off to sleep is reported by 10% of males and 18% of females
aged 65 years or older, interrupted sleep in 23% and 28% respectively, and early
morning wakening in 14%.4 The prevalence in chronic pain and cancer patients
(and their family caregivers) is 40–50%.4,5 Though obtaining a ‘normal’ duration
of sleep objective measures indicate good sleep efficiency but high levels of sleep
fragmentation and movement.5 Sleep is not perceived as being of good quality.
Sleep deprivation has considerable effect on functioning. Mood, cognition and
motor performances are adversely affected, and coping strategies are seriously
undermined. The onset and maintenance of sleep are not passive processes. A
combination of cerebral competency and good habits are required. Sleep distur-
bance in critically ill patients is due to the noisy and intrusive environment, the
medications used (see Table 10.1) and the disease (particularly if respiratory).6
The pattern of the insomnia indicates possible aetiology. Initial insomnia, the
inability to fall asleep when desired in the evening, is the most common form
of insomnia. Sleep hygiene habits such as a regular bedtime, avoidance of caf-
feine and fluids over early evening, using bed for sleep and intimacy only (and
not TV or reading), mild exercise, and a warm milk drink on retiring may all
be upset by the inconveniences of illness. Opportunities to sleep during the day
induced by fatigue and boredom also unsettle habitual rhythms. An unfamiliar
(hospice) bed, differing temperature, noise and lighting levels all may contribute
negatively (or beneficially). Unrelieved symptoms of illness such as pain, dys-
pnoea, vomiting, itch and diarrhoea are liable to interfere with sleep initiation.
Corticosteroid, diuretic, psychostimulant and sympathomimetic medications,
and alcohol or benzodiazepine withdrawal states, can disrupt the onset of sleep.
Very short-acting hypnotics can result in rebound prior to morning. Akathisia,
induced by anti-emetics or antipsychotics, can escalate nocturnally. Hiccups
tend to disappear at sleep onset (though they can disrupt its onset) and do not
influence established sleep.7 Prolonged bed rest can have a sinister effect on sleep.
Lying flat unleashes thoughts (hence the analyst’s couch). Psychological issues
often declare themselves in the quiet of night, when visitors have gone home and
tiredness encourages reflection and regression. Anxieties and fears during the
night, however, present a psychotherapeutic opportunity for the ‘night nurse’.
The fear, sometimes the hope, of dying in sleep is prevalent, as is the concern
that awakening won’t happen the following morning. These concerns are real
for those experiencing dyspnoea. Physiologically, respiration slows with sleep,
as the central drive in response to carbon dioxide stimulation is muted, further
TABLE 10.1 Medications and sleep
REM SWS NREM Total sleep Sleep Dreaming Nightmares/ Fragmented Insomnia Hypnotic
stage 2 time latency parasomnia sleep effect
Opioids ↓ ↓ ↓ ↑ ↓ + + +
Benzodiazepine ↓ ↓ ↑ ↓ + +
Non-benzodiazepine ↓ ↑ ↑ ↓ +
hypnotic
Tricyclics ↓ ↓ ↑ ↑ ↓ ± + +
SSRIs ↓ ↓ ± + +
Antipsychotics ↓ ↑ ↓ + +
Anticonvulsants ↓ ↑ ↑ ↑ ↓ + +
L-dopa ↓ ↓ + + + +
Psychostimulant ↓ ↓ ↓ ↑ + +
Alcohol ↓ ↑ ↓ ↑ + +
Corticosteroid ↓ ↓ ↑ ↑ + + +
NSAIDs ↓ ↓ ↑ + +
Beta-blockers ↓ + + +
±: dreaming occurs at subtherapeutic doses.
SLEEP, SEDATION AND COMA
141
compromising oxygenation. Total sleep deprivation is less disturbing than par-

tial deprivation, and actually enhances mood. As an antidepressant therapy it is
very difficult to enforce for more than a few nights. Sleep rebound consecutive
to sleep deprivation produces an analgesic effect similar to that of paracetamol
or a NSAID.2
Fitful sleep occurs in the anxious. The restless legs syndrome (RLS) may
affect 10% of those over 65 years. Precipitated by rest, and relieved by activity,
the discomfort is often described as a crawling and tingling sensation in the calf
or thigh. The most severe symptoms tend to occur between midnight and 1 am.
‘Jumpy’ legs responds well to dopaminergic agents; however, both opioids and
benzodiazepines may help. In palliative care RLS is often serendipitously treated.
The periodic limb movement syndrome (PLMS), a rapid stereotypic flexing of the
legs associated with repeated awakenings from stage 2 sleep, may be associated
with uraemia, neurological diseases, tricyclic antidepressants and stimulants.
REM-sleep behaviour disorders (RSB) may occur in neurodegenerative disor-
ders. Pontine damage results in a failure of skeletal muscle inhibition during
sleep, so dreams are able to be enacted. The primary treatment is clonazepam,
sometimes a medication regime already established. Palliative care patients are
at risk of sleep-disordered breathing conditions. Obstructive sleep apnoea occurs
more frequently with age and obesity (induced by corticosteroids). Snoring
may be noted by others, daytime drowsiness is often the presenting symptom.
Central-acting medications, including opioids,8 are likely to enhance the propen-
sity of apnoea. Awaking hundreds of times during the night severely destroys the
recuperative functions of sleep. Early morning awakening (terminal insomnia)
may be habitual. It can also be a symptom of a major depressive episode.
The management of insomnia is directed by the aetiology. Improved sleep
hygiene, relaxation, symptom relief, supportive psychotherapy, short-term hyp-
notics and antidepressant medication are some of the possible interventions.
Cheerfulness is discordant with usual feelings of bedtime, and negative thoughts
may actually promote the initiation of sleep. Long-term hypnotics cause reduc-
tions in stage 3 and 4, the most restful period of sleep, so much sleep is spent in
stage 2. Tolerance occurs within weeks, thus efficacy tends to be lost (except for
parasomnic symptoms). Methylphenidate, which reduces daytime naps, may
improve nocturnal sleep.9 Melatonin (0.5–6 mg nocte) has both phase-shifting
and sleep-promoting properties. It is difficult to anticipate response or determine
at what time melatonin should be administered. After ingestion of melatonin
the patient needs to lie flat in a darkened room awaiting sleep. Thalidomide
was initially marketed as a hypnotic, and this effect can be a bonus when used
as chemotherapy. Alternative medicines such as valerian, kava and chamomile
may be effective.
SLEEP, SEDATION AND COMA 143
Hypersomnia (drowsiness)
There is a normal circadian propensity to feel sleepy in the early to mid after-
noon. In the general population, 11% of women and 6.7% of men reported
daytime sleepiness most days.10 Drowsiness, mental blunting or torpidity (a mild
reduction in alertness) may be disease related, symptomatic of early delirium,
or a consequence of medicinal oversedation. Dissociative type disorders of con-
sciousness are not usually encountered in palliative care practice. Disease burden
and fatigue cause excessive daytime sleep. Cerebral injury and degenerative
disorders usually cause hypersomnia (and REM behavioural disorders) rather
than insomnia. The fatigue associated with CNS damage is profound, account-
ing for excessive sleep. Returning to infantile sleeping patterns can occur in the
twilight of life. Hypersomnia is a symptom of atypical (hibernatory) depres-
sion. Sedative adverse effects of medications are potentially correctable, and
should be considered in all such clinical situations. Tricyclic antidepressants,
anti-emetics (cyclizine, metoclopramide), antipsychotics (levomepromazine),
benzodiazepines and opioids can all have residual daytime effects. SSRIs occa-
sionally are associated with daytime sleepiness, perhaps in part because of
insufficient sleep. A few escape the worries of life by sleeping (and requesting
sedation) and withdrawing (often an indication of depression). Excess sleep,
more than 10 hours in normal persons, can be associated with the ‘blah’ syn-
drome, which consists of tiredness, lethargy and difficulties in thinking and
getting going in the morning.11 Oversleeping does not refresh.
Phase disturbance
Deep sleep by day and interrupted sleep by night is a pattern frequently encoun-
tered with involvement of the CNS in the disease. Brainstem sequelae of cerebral
haemorrhage and trauma can result in states of prolonged wakefulness. Acute
mania needs to be excluded in these patients. Delayed sleep phase syndrome
(DSPS), a circadian rhythm disorder, has a familial propensity, is typical of ado-
lescence and is occasionally seen in palliative care settings. Delirium, cerebral
metastases and advanced dementia may be associated with a reversal of the
sleep–wake cycle. This syndrome is particularly disruptive to institutional liv-
ing and notoriously difficult to correct. Bright light modulates the synthesis and
release of melatonin, and depending on the time of exposure, light can either
phase advance or delay circadian sleep rhythms. Melatonin is most active at the
nadir of temperature (about 4 am). With light therapy and melatonin, response
rates are about 50%.12 Attempting to phase shift in a palliative care setting is
unrealistic. Sedating medications tend to fade after only a few nights of response
as the biological cycle reasserts dominance.
Parasomnia
Parasomnias are not uncommon in palliative care, particularly in those with
early CNS disease involvement. Medications increasing stage 3–4 of sleep,
such as antipsychotics, can increase the frequency of parasomnia in susceptible
persons. Sleep paralysis may occur when falling off to sleep and awakening.
There is a dissonance between the level of alertness and muscle atonia. It may
be associated with hypnagogic (at sleep onset) and hypnopompic hallucinations
(on awaking). Sleep paralysis, if not previously experienced can be terrifying.
Sleep walking (somnambulism) can rarely cause accidental injury. Sleeptalking
(somniloquy) occurs in stage 1, and despite the fears of the patient, it is gener-
ally difficult to comprehend and very seldom, or never, are important aspects of
emotional life revealed. Night terrors (pavor incubus) tend to occur early into
the night during stage 4 non-REM sleep, and result in waking frightened and
aroused with some recall of the content of the dreaming. Benzodiazepines block
stages 3–4, are very effective treatments for night terrors, and do not therapeuti-
cally fade. Reactivation of PTSD symptoms, particularly night terrors, may occur
during severe and life-threatening illness. Hypnic jerks or startled movements
falling asleep are common and harmless.
Dreaming
Dreaming occurs mostly during REM sleep. If woken during this phase, recall
of the dream is easier. Rehearsal of the dream content immediately upon waking
can prevent mentation rapidly slipping from the memory. Dreaming rehearses
and reworks events of the day and the entire life in an attempt to find solutions to
concerns or predicaments encountered. It allows ‘cerebral practising’ of actions
prior to executing the particular action. Nightmares (or frightening dreams)
occur more frequently towards the end of the night, and may provoke waken-
ing. Many psychotropic medications suppress REM sleep (see Table 10.1), which
probably does not assist psychological adaptation and adjustment. Suppression
of REM sleep causes nightmares, possibly due to increased REM intensity over
shorter periods.6 Nightmares are particularly associated with drug withdrawal
states (and REM rebound).
TWILIGHT STATES
Stupor and persistent vegetative state (PVS)
Between alertness and coma are a variety of altered states of consciousness.
Stupor is a state of unresponsiveness from which the patient may be aroused
by vigorous and repeated stimuli. In palliative medicine it is usually a condi-
tion which progresses to coma. The moments of lightened awareness lessen,
and responsiveness fades. PVS after severe brain injury consists of wakefulness
without awareness. The eyes open spontaneously in response to verbal stimuli,
the sleep–wake cycle exists and autonomic functions are maintained. No motor
or comprehensible verbal output is possible. The minimal conscious state refers
to a similar clinical state in which some semblance of response occurs. Slow
visual tracking gives the appearance of communicating, though this is not able
to be sustained. In the locked-in syndrome, consciousness is preserved but there
is an almost complete inability to respond, only eye movements and blinking
being preserved.
Family distress is profound. Visits and care are incredibly arduous. The
relatives are relieved that the patient has survived, uncertain how impaired the
comprehension and communication really is, and dismayed by the existence of
their loved one. Most family members overestimate the retained communica-
tion abilities. Intuitive forms of communication occur between family members,
but the misinterpretation of reflexive movements as communication is likely.
Isolated case descriptions of severely brain impaired persons portraying some
meaningful communication have further reinforced the anxieties and appre-
hensions of both relatives and staff.13 There is often a significant discordance
between staff and family about the quality of retained communication. This may
have implications for care and its continuance. PVS tends to clinically plateau at
about 6 months, but indications of the extent of permanent impairments are not
usually offered until after 12 months have elapsed. Until this time the optimism
of the family is understandable. Over time (several years often), families visit
less frequently and for briefer periods, as reality bites and lives proceed. This
is not generally because of fading affections, but rather the necessities of their
lives. Issues concerning guardianship, advance directives and site of ongoing
care need to be gradually addressed within a supportive family therapy model.
With good nursing and medical care these patients may survive years, even
decades.
Lightening before death
We have all observed the mind clear in an extraordinary manner in the

last hours of life . . . we have seen it become capable of exercising a subtle
judgement.
Halford wrote in 1842 this clinical description of ‘lightening up before death’.14

This phenomenon is occasionally noted in palliative care units (particularly by
nursing staff ). However, this may be less frequent in modern practice because of
the increased use of sedatives. It is often associated with delirium, it is a mortal
sign and its occurrence seems impossible to predict. Reduced need for analgesic
medications and the short burst of increased vitality immediately before death
has been reported, and probably refers to the same clinical event.15 Hughlings
Jackson’s theoretical understanding of CNS functioning may account for this

phenomenon (see Chapter 9).16 When it does occur it is a wonderful occasion.
Near-death experiences
The literature on near-death experiences (NDE) is generally outside, rather than
within, medical publications. Described since antiquity, there are some consist-
ent and universal features. Apparently when dying, or near to death, enhanced
perception to light and cognitive powers occur. There are varying reports of
types and intensity of lights. Enhanced speed and clarity of thought and memory,
positive emotions and a belief in having left the body and seeing it from above
are the typical symptom clusters in NDEs.17 The theories proposed to account
for this phenomenon are transcendental, psychological and physiological (and
combinations of these). Hypoxia must be a component of the cause. Hughlings
Jackson’s concept of hierarchical dissolution of the damaged nervous system and
compensatory positive symptoms would appear consistent with the experiences
detailed. Psychological reactions following surviving the near-fatal event must
influence how the experience is recalled and processed.18 Mystical and religious
interpretations are likely to be also relevant. The mortality associated with pallia-
tive medicine would limit the frequency of such a phenomenon occurring. The
relationship of NDE and ‘lightening before death’ may be that they are variants
of the same process.
Last words
It is reported that 30% of patients are alert until moments before death.19 The
very high incidence rates of terminal delirium, coma and medicinal sedation
preceding death may suggest this figure is generous.20 A more recent observation
reported only 8% awake just prior to death.21 Notable actual deathbed speeches
are probably rare. ‘Kiss me Hardy’-type exclamations may be, more commonly
than not, mythological. A quoted medical informant in 1961 claimed to have
attended 500 deaths without having heard a single memorable utterance.22 In the
ancient world, before death had been medicalised, such events were described
and documented. Some Buddhist traditions hope for full lucidity and awareness
at the moment of death as an important component of a satisfactory reincarna-
tion.23 The Roman Catholic last rite provides a final opportunity to be forgiven
for sins committed, and presumes clarity and presence of mind. In its endeavour
to relieve the suffering of dying, palliative care may also be altering some of
nature’s kind tricks.
TERMINAL RESTLESSNESS
‘Terminal restlessness’ is a term commonly used to refer to unsettled behav-
iours during the last few days of life. Consistent clinical descriptions and valid
diagnostic criteria are lacking. Terminal anguish, terminal agitation, terminal

delirium, agitated delirium and predeath restlessness are other descriptors of this
state. The symptoms include irritability, anxiety, worry, unease, anguish, inatten-
tion, hallucinations and paranoia.19,24–26 The physical signs include restlessness,
fidgeting, purposeless yet coordinated movements, tossing and turning, trying to
get out of bed, moaning, crying out, grimacing, jerking, myoclonus, confusion,
picking at the sheets, cognitive impairment and aggression.24,25,27 The essential
features are motor restlessness, emotional distress and delirium.28 Attempts to
develop an objective observer-rated instrument to measure terminal restlessness
have not been successful.26 The prevalence rate during the last 48 hours of life is
reported to be 42%.29
Terminal restlessness is a pseudo-diagnostic term, used predominantly by
nursing staff, referring to several conditions causing this array of symptoms
and signs. The primary differential diagnoses include poorly controlled pain or
discomfort, delirium, medication-induced akathisia, and psychological distress.
The reported foci of the psychological distress are the fear of (impending) death,
anguish about the life lived, and spiritual issues.30 Fears of losing control, letting
go and the actual process of death are reported themes, as are such issues as
‘unfinished business’, guilt and ‘skeletons in the cupboard’.19 The initial clinical
task is to establish the primary diagnosis. Delirium management differs from
managing the fears of dying. In practice, anxiolytic and sedative medication may
be resorted to rather too promptly.
PALLIATIVE SEDATION
Death and his brother Sleep.
Percy Bysshe Shelley (1792–1822)31
Death from malignant disease is not always the calm, dignified process so often
portrayed on stage and screen.32 The last 48 hours of life may be difficult for 36%,
and death ‘non-peaceful’ for 8.5%.29 Victorian physicians recorded the invariably
peaceful deaths of patients,33 perhaps in part due to the liberal use of opioids at
that time. It may be that modern oncological practice, which has the ability to
prolong the life of some cancer patients, is elongating and complicating dying.
Sustained and aggressive treatment of the primary malignancy increases the
prospects of eventual multi-organ complications. Most patients with cancer do
die with comfort and dignity due to the combination of natural processes and
medicinal palliation. A minority suffer grave symptoms that defy the skills of
multidisciplinary palliative care interventions. Some patients develop intolerable
suffering despite excellent care.34 Intractable symptomatic distress may require
deep sedation in order to achieve relief. This practice is referred to as palliative

sedation, therapeutic sedation, terminal sedation or sedation of intractable dis-
tress of the dying (SIDD). Critics use the terms ‘slow euthanasia’ and ‘backdoor
euthanasia’.
Palliative sedation refers to the intentional clinical practice of suppressing
consciousness to control refractory symptoms during the last days or hours of
life, in a manner that is ethically acceptable to the patient, family and healthcare
providers.35,36 The intractable symptoms, which have proven non-responsive to
all other interventions, are contained by the induction and the continuance of
deep sedation. When there is no other medical means of relieving an unendur-
able symptom, sedation may be the humane clinical option. Intolerable suffering
is a medical emergency. It is morally reprehensible to leave a dying patient to
suffer intolerably, if there remains a medical option that may ease the suffering.
Injudicious use of palliative sedation, or the withholding of it, are unacceptable
practices.36 It is crucial to ensure that the symptom is relieved by the sedation,
rather than sedating the patient merely to the depth that they are unable to report
or communicate their distress. Deep sedation may need to be maintained until
death; the duration is usually in the range of 1–6 days.32
The intent of sedation is to ‘kill’ the symptom, and not the patient. Palliative
sedation is not ‘past cure, past care’ (Michael Drayton 1563–1631).37 The popu-
lar presumption is that sedation hastens the end of life. A WHO definition of
palliative care incorporates the phrase ‘neither hastening nor postponing death’.
Deep sedation does not result in a quicker death.36,38,39 Deep sedation for ter-
minally ill cancer patients prolongs life, perhaps for up to a few days.36,40–42 The
small risks of the procedure such as encouraging a DVT, inducing aspiration
and respiratory distress, or haemodynamic compromise need to be considered
for these could hasten death.36 The dose of opioid and its rate of increase do not
influence survival.40 The relief of symptoms afforded by the sedation presumably
allows greater physiological and psychological comfort while awaiting nature’s
determination of the time of death. Good nursing care to prevent decubitus
ulceration and aspiration is essential. Other life-prolonging interventions have
generally at this stage been withdrawn. Palliative sedation may place additional
stress on the tired and grieving relatives, by now accepting of the inevitability of
the impending death. It also allows an opportunity for the attending family to
pause and regroup before the actuality of the death.
Palliative sedation is not physician-assisted euthanasia (PAE). The intent of
PAE is to kill the patient (and by this process the intractable symptom). The
method is to choose a lethal dose of a medication, rather than a dose that needs
to be titrated depending on response. PAE is not a medical intervention.43 Legal
decisions in both the UK and the USA precisely differentiate palliative seda-
tion and PAE on these grounds.34 The Doctrine of Double Effect discriminates
terminal sedation and PAE in terms of the intention to kill. This venerable Roman
Catholic principle, originally attributable to Thomas Aquinas, a thirteenth-
century Dominican theologian, and formulated in relation to self-defence,44 is
internationally accepted as a sound ethical basis for this clinical predicament.
According to this doctrine (see Box 10.1), if the intent is to achieve a good effect,
though the possibility of a bad effect is foreseen, the practice is ethically reason-
able.43 This principle is a doctor-centred concept, with no reference to the patient’s
world view. The doctor alone decides intent. Occasionally this scenario can be
discussed with patients early in the course of disease, but in reality, and in an
emergency, the doctor’s interpretation tends to prevail. The Doctrine of Double
Effect, however, may not be essential for justification to palliatively sedate, as
opioids and sedatives have not been shown to abbreviate the last hours of life.40,42
BOX 10.1 The Doctrine of Double Effect43
An action with two or more possible effects, including at least one possible good
effect and others that are bad, is morally permissible if four provisos are met:
● The action must not be immoral in itself.
● The action must be undertaken with the intention of achieving only the
good effect. Possible bad effect may be foreseen but must not be intended.
● The action must not achieve the good effect by means of the bad effect.
● The action must be undertaken for a proportionally grave reason (Rule of
Proportionality).
A growing world literature over the last decade reveals that, in palliative care set-
tings, palliative sedation is practised with about 25% of dying patients.45–47 This
does not include the use of medications, usually low-dosage benzodiazepines,
to relieve anxiety and/or induce a night’s sleep. The first published estimate of
the prevalence of the clinical need to palliatively sedate, 52.5%, was in a home
care programme.48 Some of the variability of incidence may be related to the
type of palliative care facility,39 though cultural and individual practitioner
characteristics also influence. The commonest indication is that of irrevers-
ible delirium, a most distressing syndrome for patient, family and staff alike.
Profound dyspnoea, uncontrolled nausea and vomiting, acute haemorrhage
and intractable pain are other indications (see Box 10.2). Opioids are not always
available in many countries, and it may be that in these circumstances palliative
sedation is more freely practised. Sophisticated analgesic interventions such as
nerve blocks, intrathecal delivery systems and surgical procedures, if available,
provide alternatives to sedation. Occasionally, these techniques also prove inef-
fective. Surveys, particularly those from Southern Europe and Asia, indicate
that psychological distress or anguish is considered an indication for terminal

sedation.42 The determination of refractory existential distress is complex and
deserving of consideration if appropriate and intensive psychosocial interven-
tions have been tried and have failed.49,50,51
BOX 10.2 Palliative sedation: indications
● Irreversible delirium
● Profound dyspnoea
● Intractable pain
● Refractory nausea/vomiting
● Acute haemorrhage
● Emotional/existential anguish?
If the possibility of intractable symptoms emerging is discussed with the patient

prior to the deterioration of their health status, the clinical decision-making is
made more straightforward. This is desirable but unlikely. Reassurances of the
effectiveness of analgesia are more commonly professed by health professions in
the earlier stages of disease. Palliative medicine advertises itself positively. The
sufferer of the disease trusts and hopes that reasonable clinical control will be
maintained. Anticipating a clinical course is fraught with error. It would be bur-
densome and inappropriate to discuss these last-resort options.34 Some patients
request that if deterioration causes distress then they would prefer sedation.
Anecdotally, those persons whom have resorted to ‘sedating’ the crises in their
lives by the use of alcohol, illicit drugs or fierce denial are less prepared to live
through dying, and may request sedation. The desire to live fluctuates wildly dur-
ing a terminal illness, and requests for pharmacological oblivion probably do the
same. A request for sleep and sedation may not be accompanied by a wish to die,
but merely a desire to have some ‘time out’ from the intolerable suffering. As the
medical crisis is developing, there is often an opportunity to discuss desperate
interventions. Consent can often be obtained. The viewpoint of the relatives and
proxy are very much more difficult to interpret, and likely to be what they would
prefer if they were in that medical predicament.52 Observing as a bystander is
rather different from playing the game. The considerable emotive pressure some
relatives place upon medical staff should always be dismissed. If the patient’s
symptoms can’t be controlled by other means, sedation may be considered. A
collegial second opinion is a luxury, if available and if time permits. The family
needs to be well informed and involved in the decision-making. However, CNS
involvement of disease may lead to the patient’s perception of quality of life being
dissimilar to that of carers and others (see Chapter 12).
The method of terminal sedation demands pharmacological knowledge and

skill. The primary intention is to sedate (to settle, immobilise, induce sleep),
rather than to tranquillise or anaesthetise. Benzodiazepines are the medica-
tion of choice. They are effective sedatives at higher dose, well tolerated, safe,
and versatile with regard to form and route of administration. An antidote
(flumazenil) is available. Midazolam is preferred as it is short acting, easy to
titrate and compatible with most medications (oral and parenteral) used at the
end of life. Concerns regarding anterograde amnestic action are not relevant
in this situation. The half-life is extended in the elderly and in those in chronic
renal failure. Benzodiazepines can induce confusion at subsedative doses. Solid
and adequate dosing is necessary. Trial releases of deep sedation can be orches-
trated, if required, by withholding the dose or administering flumazenil. The
dosage necessary to induce deep sedation is variable. Subcutaneous midazolam
30–60 mg/24 hours SC is the usual range. In those with a history of alcohol or
substance use (medicinally or illicitly), the required dose may be considerably
greater. Theoretically, adding itraconazole or ketoconazole would prolong the
half-life, but often at this stage oral compliance is no longer possible. Clinical
anecdote suggests that at about 150–200 mg/24 hours SC the GABA receptors
are fully occupied, or tolerance has occurred, and alternative sedatives need to
be considered.53,54 ‘Benzodiazepine resistance’ signals the need to change the
sedative agent. Age, sex, liver disease and the genetic influences on metabolism
account for an up to 10-fold variability in dosing of benzodiazepines. Opioids
alone are ineffective sedatives, but should be continued, possibly with dose adjust-
ment, unless adverse effects or signs of overdose are observed.36 Phenothiazine
medications, such as levomepromazine, can augment the benzodiazepine with
its sedating adverse effect. Barbiturates have a narrow safety range and cause
centrally induced cardiac and respiratory depression. Chlormethiazole and
choral hydrate are difficult to obtain. Dexmedetomidine may allow ‘conscious
sedation’, a state allowing communication and cooperation, with the additional
advantages of opioid-sparing and anti-delirium effects. To date there are only
case reports of its use in palliative medicine.55 Propofol, the anaesthetic agent,
has been used to induce terminal sedation, but requires considerable skill and
anaesthetist expertise.
Good documentation and clinical transparency are necessary (see Box 10.3).
This aspect of practice remains controversial.
COMA
Physical care of the skin and preventing aspiration are essential during this phase.
The major focus of psychosocial care shifts from the patient to the relatives.
Concerns about whether or not presence or conversations can be appreciated or
BOX 10.3 Clinical questions: sedation and intractable symptoms at the end of life
● Is this a medical emergency?

● What does patient (and family) wish for/consent to?
● What is the quality of (remaining) life of patient (and relatives)?
● What are the risks and benefits of intervention?
● What are the ethical and legal considerations?
● Are there other options/opinions we have not considered?
● Is the symptom intractable or are the carers ‘stumped’?
comprehended are much to the fore. Explanation that Cheyne–Stokes respiration

is not distressing for the patient, despite the awful auditory discomfort it creates
for the relatives, is helpful. Waiting for the inevitable death, sometimes with
apprehension, sometimes with impatience, is a vigil for the family. The duration
is difficult to estimate. The disease characteristics, including the involvement of
the CNS in the disease, and the previous level of cardiorespiratory fitness of the
patient may influence longevity at this stage.
The therapeutic intent at this stage should be to assist the relatives cope,
relieve their helplessness, and foster good family time. Teaching willing family
members to assist with, or assume, some of the nursing duties is very beneficial.
It fosters physical expressions of affection, and aborts the sense of passive wait-
ing. It serves as pragmatic family psychotherapy. However, some individuals and
families find such physical chores abhorrent and too difficult. A not uncommon
reason for a terminal admission to a hospice is this. Each family has different
attributes and skills in such crises, and these should be identified and therapeuti-
cally exploited.
DIAGNOSING DYING
In modern medicine technically disguised dying is commonplace.56 Doctors
and the general public commonly share this illusion, particularly in acute care
settings. Futile interventions may be pursued with little expectation of success.
Partly this is self-protective for the patient, relatives and doctors. It allows for
procrastination and avoidance of contemplating and discussing impending
death. Patients often have a sense of impending doom. They know their physi-
ology best. There is no validated, consistently accurate and generally accepted
clinical model for predicting life expectancy in cancer and life-threatening
illnesses.56 The medical propensity is to overestimate survival time.57 Clinical
experience and brief clinical association with the patient (but not a single assess-
ment) improves prognostic accuracy.57 Clinical judgement plays a significant
part, as do various physiological and functional parameters. Ancient Greek

physicians considered offering prognoses a crucial component of the profession.
While acknowledging their task was easier, as they only had the natural history
to consider, the general public demands that modern medicine should be able
to do better. The sicker the patient, the more confident can be the prognosis.
The history over the preceding hours and days is a guide. The ‘road to death’
can lead slowly through delirium to coma, or precipitously descend. The ‘death
rattle’, cyanosis, mottling and coolness of the skin and periphery, a cold or white
nose, lower limb oedema, a weak pulse, anuria (or sudden polyuria), restlessness
and delirium (and coma) indicate that death is likely within hours.21 Intrusive
physical examination is neither appropriate nor instructive. Clinical observa-
tion, visually and with olfaction, is usually sufficient. Hippocrates described the
characteristic death facies and observed that partial ptosis during sleep or coma
was a mortal sign.58 Eyelid closure prompts sleep (by ensuring darkness), but
depends on coordinated activity of the brainstem and cranial nerves.59 A failing
brain fails in this task, and bilateral partial ptosis indicates this. Pupillary signs
are unreliable in the dying. Opioids cause miosis, but this is an all-or-nothing
sign. An ipsilateral Babinski sign is more accurate than pupillary or fundal signs
of raised intracranial pressure. Clinicians should be able to discuss frankly the
predicament with the patient and attending family if they so wish; adding the
proviso that the precise timing of death is not within medicine’s jurisdiction
allows for the unexpected.
Witnessing dying can be a profoundly disturbing event for some relatives,
and a privilege for others. The death of the patient in palliative care signals the
commencement of bereavement care. The diagnosis of dying not only ensures
sensitive and sensible clinical practice, it introduces this second clinical task of
palliative care.
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pp. 46–51.
CHAPTER 11
Neoplasms
[Brain tumours begin with an] imperceptible decline in delicate intellectual

processes and a loss of inner emotions.
Hughlings Jackson (1835–1911)1
The common tumours within the nervous system, gliomas and cerebral metas-
tases, are rarely curable.2 The most common primary brain tumour is glioblastoma
multiforme. Most high-grade (III or IV) gliomas are terminal within 1–2 years.
Brain tumours account for about 3% of cancer deaths. Though relatively unusual,
because of their typically long course, brain tumour cases are familiar in pal-
liative care settings. Nervous system metastases are 10 times more commonly
seen. Cerebral metastases occur in up to 25% of patients with cancer, two-thirds
whom are symptomatic.3 Small-cell lung tumours, melanomas and breast can-
cers commonly metastasise to the brain, but any cancer may. The prevalence
of cerebral metastases is increasing as a result of overall improved survival in
cancer patients and improved diagnostic methods.3,4 Metastatic involvement
of cancer tends to be a late complication, the exceptions being lung cancer and
melanoma. The majority of metastases occur within the cerebral hemispheres
(mainly parietal), and on detection are likely to be multiple (see Box 11.1). They
can involve the leptomeninges, the spinal cord, the brachial and lumbosacral
plexus and the peripheral nerves. Even small lesions can have disastrous effects
on quality of life. The natural history of untreated cerebral metastases is pro-
gressive neurological deterioration with a median life expectancy of 1 month.5
Older age, poor performance status and the presence of extracranial metastases
are poor prognostic factors.5 With treatment the prognosis may be 2–7 months.3
Post-mortem studies suggest up to 30% of cancer patients die with such disease
spread, of whom only 50% were symptomatic during life.6 Sixty per cent of those
with small-cell lung cancer, and 75% with metastatic melanoma have demon-
strable metastases at autopsy.3
157
BOX 11.1 Characteristics of brain metastases (adapted from reference 4)
Peak incidence
● 55–65 years
Most common tumour types (adults)

● Lung (small cell): 35–45%
● Melanoma: 10%
● Breast: 10–20%
● Colorectal: 5–10%
● Renal cell: 5–10%
Site
● Cerebral hemisphere: 80%
● Cerebellum: 15% (renal, colon)
● Leptomeninges: 8% (breast, lung)
● Brainstem: 5%
Distribution
● Multiple: 70% (melanoma, lung)
● Single: 30% (colon, breast, renal)
Presentation
● Headache: 53%
● Focal weakness: 40%
● Mental/behavioural disturbance: 31%
● Seizure: 15% (melanoma)
● Ataxia: 20%
● Aphasia: 10%
● Asymptomatic: 30%
The terminal management of malignant tumours affecting the nervous system

is challenging. The journey from acute presentation to death can be agonising.
Evaluating the benefit–risk ratio in the management of neoplasms is critically
important. The benefits of debulking surgery, radiotherapy and chemotherapy
require balancing against the adverse effects of these relatively crude interven-
tions. The introduction of a tolerable oral alkylating agent, temozolomide, when
combined with radiotherapy, has prolonged survival in malignant gliomas of
at least several months. However, the quality of remaining life also deserves
consideration. Avoiding useless ‘overtreatment’ should be the governing idea.7
NEOPLASMS 159
SYMPTOMS OF BRAIN TUMOURS

Headache
Headache occurs at presentation in 36–50% of brain tumours, and during the
course of illness in 60% (but in only 40% of those with single metastases). The
‘classic’ early-morning headache associated with brain tumours only occurs in a
minority.2 Presumably, the headache is caused by traction on pain-sensitive brain
structures such as the meninges and blood vessels.2 Early in the course of illness
the headache may clinically be indistinguishable from tension or vascular head-
ache. Assuming it is psychogenic is usually incorrect in these patients. Though
these patients are encountering multiple psychosocial stressors, the headaches
are likely to be predominantly ‘organic’. If the patient is unable to communicate
their symptoms, as may occur in the later stages, observable behavioural signs
of pain such as rubbing their head, wincing, shifting restlessly, moaning and
groaning suggest the need for improved analgesia. The facial expressions of
pain, originally studied by Charles Darwin, include brow lowering (frowning),
tightened eyelids, upper lip raising and nose wrinkling.8 Relatives are often aware
of the patient’s idiosyncratic or habitual expressions of discomfort, and this can
be most helpful to the clinician. If clinical doubt persists, erring on the side of
ensuring adequate analgesia is preferable. Severe headache is a most unpleasant
pain. A severe headache on awakening (aggravated by coughing or straining),
nausea and vomiting, transient loss of vision with papilloedema, sixth nerve
lateral rectus palsy, ipsilateral pyramidal limb signs and a deteriorating level of
consciousness are suggestive of ‘coning’ and impending death. Papilloedema is
present in only 25% of brain metastases and may be absent even when intracra-
nial pressure (ICP) is very high.
Seizures
Only about 50% of cerebral tumour patients have seizures during the course
of their illness.2 As a presenting symptom, seizures occur in 20–40%. Seizures
occur in up to 25% of patients with brain metastases.3 Seizure prophylaxis is not
necessary in those who have never had a seizure, and postoperatively, anticon-
vulsants may be withdrawn after a week. Prophylactic anticonvulsants are not
effective in preventing first-onset seizures in patients with cerebral metastases.
Not only do anticonvulsants have cognitive side effects, they may cause drow-
siness, ataxia and hepatotoxicity. There appears to be an increased incidence
of severe allergic skin reactions, such as Stevens–Johnson syndrome, in those
patients who have received cranial irradiation and are on anticonvulsants.9
However, the risk of seizures is ever-present and a further source of anxiety
for patient and caregivers. In the terminal phase, though a seizure is a rare
cause of death, the risks increase as tumour bulk increases. In dying primary
brain tumour patients, seizures were a symptomatic concern in only 10%.10
Non-convulsive status epilepticus, a rare cause of major mental status alterations

in such patients, is important to consider as it is potentially reversible.11 Oral
compliance may not be possible. Benzodiazepines are not particularly effective
anticonvulsants in the presence of structural lesions; however, they have the
advantage of route versatility and do provide a semblance of anticonvulsant
cover. Buccal midazolam is the route of choice for status epilepticus in the com-
munity. In the hospice, parenteral midazolam would be the likely first choice.
There is no demonstrable difference in anticonvulsant efficacy of the various
benzodiazepines.
Cognitive dysfunction
Language, visuospatial, memory, and executive dysfunctions may present,
depending upon the site and size of the tumour. Radiotherapy, chemotherapy,
medications (anticonvulsant, corticosteroid, opioids), post-ictal delirium and
depression may all contribute to cognitive deficits. Some may be transient though
the already impaired brain becomes increasingly sensitive to insult and less able
to recover. Cognitive dysfunction is an important determinant of health-related
quality of life and deserves rigorous assessment and, if possible, intervention.
Formal psychometric evaluation is time-consuming and expensive, and is rarely
justified in the terminal phase. Bedside assessment is usually adequate to deter-
mine the presence of cognitive impairment and monitor progression over time.
The decline of cognitive functioning in brain tumour patients is usually insidi-
ous and subtle. The early cognitive deficits may be focal. Rapid change suggests
an acute event such as haemorrhage into the tumour or medication toxicity.
Competency issues may emerge as clinical concerns.
Management is dependent on the cause of the decline. Adjusting anticonvul-
sant dosages, altering the corticosteroid regime or treating depression can result
in improvement. A trial of methylphenidate has been shown to be of benefit.12
But inevitably, there is a predictable deteriorating course as the mind of the
patient is robbed by the neoplasm.
Personality and behavioural change

Subtle coarsening of personality accompanies progressive organic disease of the
brain. The personality changes are mostly minor, sometimes only detectable to
close family. Social graces are lost, the usual consideration of others is forgot-
ten, focus becomes more egocentric, and uncharacteristic irritability becomes
apparent. Relatives comment that it is as if the patient is very tired after a hard
day or late night. The little niceties of the patient’s character are lost. There is
generally an enhancement of premorbid personality traits. The acquired and
practised refinements of adapting to the rigours and reality of life wilt under the
burden of organic pathology. The ‘organism’ reverts to basic self-preservation
NEOPLASMS 161
behaviours. The nervous system regresses to a simpler level of functioning in

order to persevere with existence.
Management is to accept these changes, and to manipulate the repertoire
if possible. Commonly, staff interpret the alterations in behaviour as attention
seeking, demanding or manipulation. Forceful, sometimes punitive, reaction
and appeals to the patient prove unhelpful. If confronted with interpersonal and
cognitive demands beyond their ability to now cope with, catastrophic reactions
can be induced. This ‘organic motor panic’ reaction consists of a transient freez-
ing of motor function and an associated state of anxious perplexity. This extreme
response to being cognitively overwhelmed is less common than the hesitant,
slowed and measured attempts to respond, which are hopefully recognised by
others as indicative of an inability to manage the challenge. By limiting new
demands and by encouraging routine these challenges are reduced and behav-
iours mellow. The same daily routine of ablutions, feeding, resting, accepting
visitors, and so forth, is preferable. Patience, persistence and gentle guidance by
staff and relatives should result in the task being eventually achieved. Attending
these patients is one of the most demanding of any nursing tasks. The need to
correctly pace the patient, intuitively coerce them at times, massage their esteem
and sometimes ginger them along are caring skills rarely found, and unfortu-
nately not well appreciated. Obviously, to find these attributes in the relatives is
chance indeed. Respite care breaks for relatives, who are simultaneously grieving
the losses they observe and feel, are essential. Many families cope remarkably
well despite the exhausting job. Institutional care, if it is available, is occasionally
the most humane option.
Medications have little role. Low-dose benzodiazepine may settle the patient.
The use of antipsychotic medication to ameliorate temper outbursts and reduce
aggressive behaviour is occasionally of benefit, though there is no evidence
to support its use, and the possible neurological side effects are of concern.
Quetiapine has the least potential to cause neurological adverse reactions. The
evidence is lacking for anticonvulsant medications for irritable aggression.
Buspirone, a novel anxiolytic agent, can rarely and unpredictably be beneficial
in these patients. Generally, psychotropic medication for organic personality
and behaviour problems is disappointing, and adverse effects are liable to be
problematic because of enhanced sensitivity.
Anxiety and mood changes

The propensity to develop sustained and troublesome anxiety, often precipi-
tated by situations, is enhanced in those with brain tumours. The situation with
depression is similar, the risk being enhanced by the multiple losses accumulated
during the illness. Anxious irritability, rather than overt misery of mood, is not
unusual in organic conditions. Both anxiety and depression are more likely early
in the course of illness when insight and judgement is retained and the devastat-
ing impact on life is able to be acknowledged. Sustained elation of mood is rare.
Assertive multimodal interventions are indicated: individual and family sup-
portive psychotherapy, support groups and medications if appropriate. Being
aware of enhanced sensitivity to the adverse reactions of medication should
encourage commencing low dosages and gradually titrating to a therapeutic dos-
age. Response rates are not particularly impressive, perhaps 40–50% in organic
mood disorders. The rate of depression in carers is increased, and their welfare
should not be neglected.
Vascular disorders
Cerebral infarction is occasionally the first manifestation of cancer though
more often embolic cerebral infarcts or haemorrhages occur in patients with
established cancer.3 Bleeding into cerebral metastases may be an explanation for
catastrophic neurological deteriorations which can occur in advanced cancer.
Hallucinations
Hallucinations may occur. They are usually visual and a part of an epileptic
disturbance.13
Fatigue
Injury or damage to the nervous system causes profound fatigue. Because the
brain has to function at increased capacity to compensate, it tires easily. Within
hours of awaking many patients feel physically and emotionally exhausted.
Frequent periods of rest need to be programmed, and do help to some extent.
When tired, emotions easily become negative and irritable. Fatigue is easily
misdiagnosed as depression. Psychostimulants warrant a trial. It is important to
withdraw any potentially sedating medications or medications prone to enhance
fatigue.
Immobility
Eventually mobility is lost for most brain tumour patients. Specific lesion sites
will cause particular losses (e.g. hemiplegia). Steroid-induced proximal myopa-
thy exacerbates mobility problems. Dependency on others is the consequence,
and for most losing physical independence is a bitter loss. Immobility heralds
the procession of disabling and life-threatening complications including decu-
bitus ulcers, venous thromboembolism, painful contractures and infection.
Physiotherapy to maintain and optimise retained function is warranted both
from a physical and a psychological perspective.14 Physiotherapists are reluctant,
but very effective, supportive psychotherapists.
NEOPLASMS 163
LEPTOMENINGEAL METASTASES
Metastasis to the leptomeninges, also termed neoplastic meningitis, is diagnosed
in about 5% of those with solid tumours and in up to 15% of haematological
malignancies. Lung, breast, melanoma and lymphomas are the most likely
associated malignancies. These metastases occur late in the course of disease.2
A diffuse, sheet-like covering of the surface of the brain eventuates, and the
symptoms may mimic meningitis. Autopsy studies indicate that in cancer
patients with neurological symptoms and signs 19% have evidence of meningeal
involvement.15 They are frequently missed in the late and terminal stage of ill-
ness, and difficult to detect even on MRI scanning. Malignant cells in the CSF
is the most useful investigation, but this is rarely appropriate toward the end of
life, for the median survival is only 4–6 weeks.15 Multiple neurological losses
such as cranial palsies, peripheral nerve lesions, cauda equina lesions, seizures
and focal neurological deficits are the typical clinical features.2 Headache is the
commonest symptom but signs on examination generally exceed symptoms.15 It
may account for a delirium or cause communicating hydrocephalus.2 Treatment
is generally not contemplated during the terminal phase of illness, other than
analgesia if pain is a feature. Corticosteroids have limited effect, but prophylactic
anticonvulsants are advisable.
SPINAL CORD METASTASES

There are few palliative care emergencies. Spinal cord compression is one. This
devastating complication is not preventable, but paraplegia may be by prompt
intervention. Corticosteroids acutely and immediate radiotherapy are the
mainstays of treatment. Very high-dosage dexamethasone, 16 mg to 100 mg IV,
can however also result in acute psychiatric side effects. Delirium, agitation,
insomnia, mania and depression can be precipitated and compound treatment
cooperation and compliance. The psychological impact of quadriplegia or para-
plegia is profound, and the care needs of the patient escalate.
NEUROPSYCHIATRIC PARANEOPLASTIC SYNDROMES

These rare encephalomyelitic syndromes are infrequently recognised by cli-
nicians. They occur in 1% of all cancers and 3% of lung cancers. They may
present before the primary tumour. The typical presentation is a subacute onset
of amnesia (mainly short-term), seizures and psychiatric symptoms.16 Limbic
encephalitis is important in palliative medicine, as delirium is the major dif-
ferential diagnosis. These include anxiety, mood lability, confusion, personality
change, hallucinations and paranoid delusions. Invariably, denial of the deficits
and confabulation cloud the presentation. Most develop progressive general-
ised neurological signs and dementia. Small-cell lung cancer is the malignancy
most often associated. It is a presumed auto-immune response. The course is
unpredictable, but generally it stabilises. Treatment of the primary tumour rarely

encourages any remission if the CNS is involved. High-dose corticosteroids are
advised, but tend to be unrewarding. Psychotropic medications may be helpful.16
Residual significant neuropsychiatric disability is the usual outcome. Brainstem
encephalitis, cerebellar degeneration, peripheral neuropathy and myopathy may
be paraneoplastic.
PSYCHIATRIC SYMPTOMS AND CEREBRAL TUMOUR LOCATION

Not only do symptoms change during the evolution of the tumours, the rela-
tionship between anatomy and clinical symptoms is relatively imprecise. The
compensatory mechanisms of the CNS to adjust to focal lesions are extraor-
dinary. Frontal lobe tumours are typically associated with marked executive
dysfunction and personality change, disinhibition or apathy in 90%.17 Temporal
lobe lesions are associated with seizures, often psychomotor in character, and
depression. Schizophrenia-like symptoms may be convulsive in origin in these
patients. Non-dominant temporal tumours may cause affective syndromes.
Parietal tumours rarely produce psychological changes though the dysphasic,
dyspraxic symptoms can be mistaken for conversion syndromes or dementia.
Occipital tumours are very rarely correlated with mental changes. Corpus cal-
losal tumours are highly correlated with cognitive difficulties. Diencephalic
tumours can present with amnestic difficulties including an inability to fixate
current events and confabulation, with retained remote memory and other
cognitive functions.13
THE EFFECT ON THE FAMILY

The often long and gradual decline in health and apparent quality of life is stress-
ful for all. ‘Social death’ occurring months or years before biological death robs
the family of the person ‘they know’.18 The loss of ‘personhood’, competency,
appearance and vitality are cruel. Changes in family roles occur as communica-
tion is impaired, marital and parental relationships dissolve, finances evaporate
and the sheer physical burden of care becomes tiring. The emotional impact
upon the family is immense. Faiths and beliefs are challenged by the tragedy.
There is, as expected, a wide range of opinion among relatives regarding the
trade-off between length of life (and active treatments) and quality of life.19
Minimal suffering and distress, lack of psychological and cognitive changes,
and time spent free of disability, are the outcomes appreciated by relatives, but
difficult for the clinician to predict.19 Support is deserved. Most helpful is infor-
mation about the disease and treatment, advising the need and right of respite
or institutional care, and guiding what is a complex anticipatory grief process.
The reality of the predicament is often overwhelming. At the deathbed, family
coping difficulties were reported in 85% of families.10
NEOPLASMS 165
TREATMENT COMPLICATIONS
Corticosteroids
The therapeutic benefits of corticosteroids in cancer care are important and at
times dramatic. Corticosteroids will produce clinical improvement in 60–70%
of those with cerebral metastases, usually within 6–24 hours following the initial
dose, with maximal effect in 3–6 days.3,4 Those with symptoms reflecting general-
ised cerebral dysfunction and raised intracranial pressure from oedema respond
more frequently than those with focal neurological symptoms. Corticosteroids
double median survival of these patients to 2 months. The unwanted side effects
can be unpleasant, disfiguring, and disabling. In neoplastic disease longer-term
use is generally required and dose and adverse effect profile become major
management issues. The appropriate dose of corticosteroid to reduce oedema
surrounding tumours is uncertain. A solitary controlled trial concluded that
4 mg, 8 mg and 16 mg of dexamethasone were equivalent over a 4-week period,
though obviously adverse reactions increased with a higher dosage.20 It is clini-
cal convention to attack with a large dosage, often 16 mg, and then tail the dose
slowly towards the lowest possible therapeutic dose. Dose and duration of
therapy are important influences upon the adverse effect burden. Psychiatric
detrimental effects of steroids occur in 25% and are severe in 5.7%.21,22
Psychiatric side effects

Endogenous and exogenous corticosteroids may affect mood, though ‘steroid
psychosis’ is a misnomer. The rate of depression in Cushing’s syndrome is
reported to be 50–81%, and mania 27–31%.23,24 Mood normalises after the corti-
sol returns to normal. ‘Stress’ induces glucocorticoid release. In major depressive
disorder, hypersecretion of cortisol occurs. The effects on the brain of cortisol
vary. In acute and dangerous situations, it prepares the body and mind for ‘fight
or flight’. If sustained, high cortisol has negative effects on functional activity of
the brain, specifically a loss of control of mood (from an evolutionary perspec-
tive, a resignation).23 The mechanisms of acute and chronic steroid side effects are
likely to be different. The acute effects are from a direct upregulation action on
the glucocorticoid receptors of noradrenergic and serotonergic neurotransmit-
ters, and/or a normalisation of the hypothalamic–pituitary–adrenal (HPA) axis
(by negative feedback).23 The chronic effects may be due to neurotoxic actions of
the glucocorticoids on the hippocampus, reducing glucocortisol receptor plastic-
ity and causing ‘steroid resistance’.23–25 Steroids are poorly absorbed by the brain.
High dosage and several weeks of use may be required to induce these changes.
Of patients with psychiatric reactions, 77% are on doses greater than 40 mg pred-
nisone.26 The literature on ‘steroid psychosis’, from the initial paper in 1952 until
currently, consistently describes two syndromes induced by corticosteroids.27
These are a rapid-onset mild enhancement of mood and well-being, tending to
fade over a few weeks, and a slower-evolving fluctuating mood disorder, often
associated with psychotic symptoms.26 These problems are commoner in women,
at least in the non-cancer literature. However, diseases requiring steroid therapy
are more prevalent in women and these diseases themselves are prone to psychi-
atric complications (e.g. systemic lupus erythematosus [SLE]).
Corticosteroid euphoria
This is frequently observed in palliative medicine. Terminally ill patients are pre-
scribed steroids for many non-specific symptoms such as fatigue, anorexia and
‘low mood’. The indication to boost/improve mood with steroids was applied to
22% and 12% of hospice patients.28,29 Improvement of mood in similar patients
occurred in 40%, 59% and 71%, though it tended to fade over several weeks.29–31
The early studies proposed that the euphoria was secondary to improved physical
well-being.27 However, in asthmatic patients, mood elevations, but not mania,
occurred before the improvement of respiratory function (within a week) in
response to approximately 40 mg of prednisone, and settled promptly with dis-
continuation.32 There is a suggestion that depressed patients are more likely to
get such a response.32 A modest dose (3–4 mg/day dexamethasone) for 4 days
has been shown to improve mood and augment antidepressant action in patients
with major depression.33,34 Response rates of 37% and 60% respectively were
noted. Dose does not appear to be relevant in the initiation of this reaction.26
Insomnia and anxiety induced by steroids may merely be an effect of the physi-
cal and mental stimulation of steroids. Corticosteroid euphoria may be induced
rapidly in physically compromised ‘low-spirited’ patients. The benefits seem
to fade over several weeks and subsequently the risks of harmful effects of this
therapy would seem to increase.
Steroid-induced bipolarity
Mania is the best known, or most memorable, psychiatric adverse effect of ster-
oids. Of the serious psychiatric effects 75% involved mood disorder.26 Actually
depression may be commoner.21 Mania is reported to occur in 10%, 22% and
40%.21,35,36 Depression has been reported in 32%.21 The predominant features of
the mood disturbances associated with steroids are rapid fluctuations, mixed
mood states and bipolarity.24 Suicides have been reported.22 The onset of severe
effects appears to take at least a week to emerge, if not longer.24,36 The clini-
cal similarities of these cases to bipolar disorder are ‘striking’,24 as they are to
postpartum mood disorder. Psychotic symptoms, described in 11%, occurred
as a feature of mania in 40%.21,36 The descriptions of steroid-induced delirium
occurring in 8–25% may be accounted for by this, or by the reality that most
of these patients also have severe other medical illnesses.21,26 Mood disruption
is unpredictable, with a possibility of multiple episodes lowering the threshold
NEOPLASMS 167
for future episodes.26 There is no clear indication that a past psychiatric history
increases the risk.21,26 A report of tricyclic antidepressants aggravating the condi-
tion suggests the possibility of an induction of rapid cycling mood fluctuations
by steroids.37
Steroid dementia
Cognitive deficits have been reported, specifically reversible memory impair-
ment of declarative (verbal) type, suggesting hippocampal involvement.21,38 There
is a case report of six cases of slow resolving ‘dementia’ on long-term steroids,39
and another of a single patient.22
Steroid dependence
There is a reluctance to cease steroids in palliative medicine practice.30 There
are case reports of psychological dependence, referring to depressive symptoms
surfacing on withdrawal.21,26,40 This may be secondary to the release of the sup-
pression of the HPA axis.21 Physiological dependence is of course a prominent
clinical issue. Abrupt cessation after more than a week of therapy can result in
adrenal insufficiency, hypotension and death. In palliative care, discontinuation
can be mistakenly implicated as the cause of terminal deterioration,28 and it has
been suggested that this increases terminal restlessness.29 Fatigue, malaise, ano-
rexia, pyrexia, discouragement, myalgia and arthralgia (pseudo-rheumatism) are
anecdotally reported following reduction and withdrawal of steroids.
Body image
Moon facies and weight gain induced by steroids are psychologically disappoint-
ing for all patients.
Management of corticosteroid-induced psychiatric complications

Tapering the dose and the administration of psychotropic medications for symp-
tom relief are the two major options. The combination is more effective than
these treatments individually.22 Response within a few days and full recovery is
usually expected.22,24,37 Mania takes longer to settle than depression and delirium,
as is to be expected.26 Drug interactions with anticonvulsants and ketoconazole
need to be recognised. TCAs may induce hypomania. SSRIs are probably less
likely to do so, but antidepressants should only be used cautiously. Haloperidol
is the most commonly used antipsychotic. There are reports of olanzapine and
risperidone being used.26 Lithium carbonate prophylaxis is useful in preventing
psychiatric effects of pulse steroids in multiple sclerosis, but has no role in pal-
liative care.
RADIATION THERAPY
The longer survival of cancer patients is demonstrating that the longer-term
neuropsychiatric complications of nervous system irradiation, especially whole-
brain radiotherapy, can be most disabling. Cranial irradiation increases survival
of those with cerebral metastases from 1 month to 4–6 months.41 Response rate
in terms of neurological improvement in cerebral metastases is approximately
50%, and even better relief with other symptoms (headache, nausea) is achieved.4
Clinically differentiating the effects of radiotherapy from those of the primary
illness and other treatments can be difficult.
Radiotherapy to the nervous system results in initial amplification of symp-
toms because of secondary local oedema. Drowsiness, headache, nausea and a
worsening of pre-existing focal symptoms result.42 Brain herniation is an acute
risk. Corticosteroids can minimise these. The beneficial effect may take at least
10 days following the completion of radiotherapy to declare itself. Subacute
encephalopathy typically presents 1–6 months following completion of radio-
therapy. Headache, somnolence, fatigue and deterioration of pre-existing deficits
occur secondary to diffuse demyelination.42 This is spontaneously reversible
over several months. Late delayed consequences may appear after 6 months,
and these are irreversible and often progressive.42 Damage to white matter
causes symptoms ranging from mild lassitude and minor cognitive slowing to
a severe dementia. The prevalence of these complications is uncertain, perhaps
a few per cent. Changing technology and methods make it difficult to interpret
retrospective studies.43 Dose and dose scheduling, concurrent chemotherapy
and older age are risk factors for these complications. The risks with focal and
stereotactic radiation are negligible.
Management options are very limited. Corticosteroids, anticoagulation (to
improve microvascular circulation), psychostimulants and occasional surgical
excision of a necrosed area are a few potential management options. The tragedy
of iatrogenic complications is obvious, and in these cases a very high cost of the
prolongation of life.
CHEMOTHERAPY
Chemotherapy has an underestimated role in treating patients with brain metas-
tases. Death for half of these patients is caused by the systemic disease, and this
treatment may influence survival.3 The blood–brain barrier is largely destroyed
by brain metastases, and drug efficacy is related to tumour sensitivity rather than
ability of a drug to cross the barrier. It has been considered that the usually used
chemotherapeutic agents do not cause ‘chemo-fog’. More careful neurocognitive
testing is indicating minor cognitive deficits.44 Often a good pretreatment cogni-
tive baseline is contaminated by the effects of anxiety, and differentiating disease
and treatment consequences is difficult. ‘Chemobrain’, a decline of executive
NEOPLASMS 169
function and short-term memory after chemotherapy, has been particularly

considered in women with breast cancer.3 It has been shown that there is little
correlation between the patient’s perception of their cognitive functioning and
neuropsychological performance,45 though neuropsychological assessment may
not be able to identify such subtle cognitive deficits. Some of these deficits may be
pre-treatment paraneoplastic changes or stress related. Lung cancer patients have
pretreatment impairments of memory and executive function.46 Unfortunately,
there is growing evidence that ‘chemo-fog’ is a genuine complication, that it
may be common, enduring, and adversely affecting the quality of life of cancer
survivors.47 Pharmacological management strategies including neuroprotective
agents, psychostimulants and cholinesterase inhibitors, have yet to show con-
vincing preventative or treatment effects. Cognitive retraining and rehabilitation
strategies may be more promising.47 Many chemotherapy agents have major
acute neurological side effects including painful peripheral neuropathy (vinca
alkaloids), cerebellar ataxia (fluorouracil) and leukoencephalopathy (meth-
otrexate). The advent of temozolomide is allowing tolerable chemotherapeutic
adjuncts to surgery and radiotherapy.
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18 Sweeting H, Gilhooly M. Dementia and the phenomenon of social death. Sociol Health
Illn. 1997; 19: 93–117.
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therapy for malignant cerebral glioma. J Neurol Neurosurg Psychiatry. 2005; 76: 555–61.
20 Vecht CJ, Hovestadt A, Verbiest HBC, et al. Dose–effect relationship of dexamethasone
on Karnofsky performance in matestatic brain tumours. Neurology. 1994; 44: 675–80.
21 Ismail K, Wessely S. Psychiatric complications of corticosteroid therapy. Br J Hosp Med.
1995; 53: 495–9.
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NEOPLASMS 171
34 Dinan TG, Lavelle E, Cooney J, et al. Dexamethasone augmentation in treatment-

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CHAPTER 12
Cognitive dysfunction and dementia
A crust of indifference is slowly creeping around me, a fact I state without

complaining. It is a natural development, a way of beginning to grow inor-
ganic – the detachment of old age I think it is called.
Sigmund Freud (1856–1939)1
The rapidly rising rates of dementia worldwide, a reflection of ageing populations

and lifestyle, signal an emerging crisis. ‘Too few cradles, too many graves’ will be
an issue for future generations. Palliative medicine does not attend to patients
with dementia. There are a few exceptions,2 and recent increased interest in sup-
portive and palliative care for persons with dementia.3 A palliative approach to
dementia care and partnership, rather than specialist palliative care, may offer
the best benefit to the burgeoning services for the elderly. As yet there is a pau-
city of good-quality evidence to support a palliative approach to dementia care,
though positive indications of efficacy.4 Patients suffering cancer also may be
experiencing age-related cognitive dysfunctions and treatment-related cognitive
deficits (see Chapter 11). Cognitive failure impacts upon coping with the dying
process, sometimes aiding it, mostly not.
COGNITION AND PAIN

Older persons tend to be more stoical about pain. Pain is expected and tolerated
with advanced age. They complain less; sometimes using words such as ‘aching’,
‘soreness’, and ‘discomfort’ provokes acknowledgement. The prevalence of pain in
nursing home residents, though difficult to accurately ascertain, may be as high
as 50%. Patients with cognitive impairments are less likely to receive analgesia,
and the risk of undertreatment increases with the severity of dementia.5,6 In
patients with dementia expressions of pain may be different and difficult to inter-
pret. Analgesics may be overused or underused as a consequence. If the patient
is able to communicate, self-report rating scales (e.g. visual analogue scales)
173
are used. These target sensory-discriminative aspects of pain, its presence and
intensity. If non-communicative, observatory scales are used and these provide
information about motivational-affective aspects of pain. Facial expressions are
reliable indicators. Pain can affect any behaviour, so it is useful to have a baseline
of eating, sleeping and exercising patterns. A change in a behavioural pattern may
indicate pain (and certainly distress, of which pain may be a cause). However,
no change may not reflect the absence of pain.5 There is not a specific behaviour
that solely indicates pain. Atypical responses such as frowning, combativeness,
withdrawal and agitation may signal pain. Guarding, bracing, moaning, fidget-
ing and muscular tenseness are less indicative of pain and may be symptoms
of extrapyramidal dysfunction or other distress. Autonomic responses such as
changes in blood pressure and heart rate are not particularly sensitive indica-
tors.5 Though pain thresholds are not different in Alzheimer’s dementia (AD),
pain tolerance may be significantly increased.7 The pain stimulus is received
but its processing is impaired. The neurological basis for motivational-affective
processing is severely affected in AD, whereas the primary sensory areas are not.
In Alzheimer’s dementia the medial, rather than the lateral, pain systems may be
impaired. Pain is felt but experienced with less (different) distress. In vascular
dementia white matter lesions may disrupt cortical and sub-cortical connec-
tions and increase pain experienced (central post-stroke pain). Observation
is more relevant than self-report rating scales in more severely demented
patients. Basic medical and nursing procedures are surprisingly uncomfortable
(see Table 12.1).8
TABLE 12.1 Common procedures and pain (10-point numeric rating scale)8
Procedure/experience Mean pain rating

Nasogastric tube 6.9
Phlebotomy 4.6
Indwelling urethral catheter 4.3
Intramuscular injection 3.9
Mechanical restraints 2.4
Movement (chair to bed) 2.0
Chest radiograph 1.4
Vital signs taken 1.3
Waiting for a procedure 1.1
DEMENTIA
Dementia is a chronic and progressive clinical syndrome characterised by an
acquired impairment of three domains of function: neuropsychological (amne-
sia, aphasia, apraxia, agnosia, executive dysfunction), behavioural/psychological
COGNITIVE DYSFUNCTION AND DEMENTIA 175
(or more correctly psychiatric) symptoms (BPSD), and deficits in activities of

daily living (ADL) (sufficient to interfere with occupational performance and
social interactions). Dementia is distinguished from mental retardation by its
acquired nature. Demented persons are at high risk of delirium because of a low
deliriant threshold (see Chapter 9). Amnestic syndromes and aphasia are more
focal impairments. Depressive pseudodementia can mimic dementia, but the
history usually provides differentiation. These patients, unlike those with demen-
tia, complain of poor memory and provide ‘don’t know’ (can’t be bothered)
answers to routine questions. A normal shedding of interest in current world
events as terminal illness enters its final phase can be mistaken for the apathy
and disinterest of dementia. In benign senile forgetfulness (or mild cognitive
impairment), the deficits are predominantly slowing of performance, and are
non-progressive. Reversible causes of dementia are rare. The commonest type
of dementia is AD (60%) followed by vascular dementia (VD) (20%). Dementia
with Lewy bodies (DLB) accounts for 15%, and frontotemporal dementia (FTD)
5% (see Table 12.2).
The disease trajectory is slowly progressive. The rate and the pattern of this
deterioration depend upon the pathological process. Late-stage dementias are
similar, irrespective of the type of disease. Every disease is person specific, and
clinically there is huge variability. The final stage of AD may last a year or so,
and for many this is spent in institutional care. This is not usually hospice care.
In nursing home care, advanced dementia patients are not perceived as having a
terminal condition, and most do not receive optimal palliative care.13 In a tertiary
hospital, 63% of dying demented patients were assessed as having high levels of
suffering, 30% intermediate and only 7% had low levels. The majority died ‘rest-
less’.14 While there are no disease-modifying treatments available, deterioration
may be delayed by medications such as the cholinesterase inhibitors. Dementia
shortens life expectancy; the median survival time from initial diagnosis is 4
years in men and 6 years in women, and less if the age on onset is young.15 The
actual cause of death in these patients is dementia, though the event is commonly
‘pneumonia’. Precise predicting of death in advanced dementia is difficult. Non-
ambulatory patients who have lost meaningful communication, are dependent
on others for activities of daily living, are cachectic, have a fractured hip or
pneumonia, and need artificial feeding are obvious predictors,4 without being
indicative of whether it is weeks or months. Antibiotic treatment of chest infec-
tions neither relieves discomfort nor prolongs survival in advanced dementia,16
though they perhaps relieve some distress.17
Clinical assessment of advanced dementia

In palliative care settings a diagnosis is generally established prior to referral.
Cortical dementia (e.g. AD) presents with prominent memory, language and
176
TABLE 12.2 The salient features of the dementias
History Mental status Neurology Comments

Alzheimer’s disease Gradual onset Anterograde amnesia Subtle if present Commonest
(AD)
Memory and behavioural Visuospatial deficits A diagnosis of exclusion
presentation
Apraxia, agnosia,
anosognosia
Vascular dementia Abrupt onset Dependent on regions Focal deficits Differentiating AD and VD is arbitrary,
(VD) affected there is considerable overlap9
History of stroke Psychiatric symptoms
early
Stepwise progression
THE PSYCHIATRY OF PALLIATIVE MEDICINE
Dementia with Lewy Cognitive fluctuations Attention Extrapyramidal signs Identical to the dementia of Parkinson’s
bodies (DLB) disease
Visual hallucinations Visuospatial deficits Most responsive to cholinesterase
inhibitors (greater cholinergic loss)
Parkinsonism Preserved memory
Antipsychotic sensitivity
Frontotemporal Insidious onset Executive (frontal lobe) Motor weakness May evolve bulbar signs and motor
dementia (FTD) signs neurone disease (MND)10
Loss of personal/social Memory often normal Fasciculations MND may evolve into FTD
awareness
Disinhibition/impulsivity Inability to infer mental Semantic and progressive aphasia not
state of others associated with MND
Loss of judgement
History Mental status Neurology Comments
Creutzfeldt–Jakob Rapidly progressive Perplexed, apathetic Dysphagia Sporadic
disease (CJD) (a mental state
prion disease)
Mood lability Lability of mood Incontinence Acquired in 5% (diet, iatrogenic)
Myoclonus/seizures Gross global cognitive Sensory Mood lability, apathy precede neurological
deficits hypersensitivity symptoms by several months11
Cerebellar/visual Rigidity Distressing for relatives and staff12
dysfunction
Dystonia Fatal within months
Stupor
AIDS dementia Social withdrawal Inattention Ataxia Symptoms and course influenced by highly
complex (ADC) active antiretroviral therapy (HAART)
Apathy Slowed thinking Tremor
Irritability Abnormal reflexes
Huntington’s disease Dysmentia rather than a Slowing of cognitions Chorea, athetoid Psychiatric symptoms precede chorea and
dementia movements dementia
Personality change Depressed mood Rigidity
Depression Psychosis Dystonia
Psychosis
COGNITIVE DYSFUNCTION AND DEMENTIA
177
visuospatial deficits. Subcortical dementia (e.g. AIDS dementia complex [ADC],

DLB, Huntington’s disease) characteristically have impairments of speed of
cognition, executive and mood features, with less prominent amnesia. Easy con-
firmation of significant organic deficits is by using the Executive Clock Drawing
Test (CLOX) which assesses the visuospatial and visuoconstruction abilities and
the executive skills required to set a clock.18 However, it does not differentiate
dementia, delirium and opioid intoxication.19 Neither does the MMSE. A test of
category fluency (‘name as many animals as possible in one minute’, expecting
15 at least in normal individuals) is also a convenient one-minute confirmatory
test of advanced dementia.20
Management of neuropsychological impairments

Adjustment issues
Individual psychotherapeutic support, because it is difficult and unrewarding,
tends not to be persevered with. Acceptance is not mentioned in the eight-stage
process individuals are assumed to use to interpret their illness: slipping, sus-
pecting, covering up, revealing, confirming, surviving, disorganisation, decline
and death.21 Encouraging a process of narrative review, of recording life stories,
can be affirming and rewarding. Kitwood’s notion of person-centred care for
dementia, emphasising the essential humanity of the person rather than the dis-
ease and its deficits, is crucial to the maintenance of dignity and ‘personhood’.22
The loss of ‘personhood’ and ‘social death’ predate death. Caregivers considered
that over one-third of demented dependents were socially (‘as good as’) dead
prior to biological death.23
Amnesia
Memory can be unlocked by emotions, particularly negative ones.24 Anger or
sadness may unleash memories of trauma. Such memories are more forcefully
laid down originally and are more difficult to forget. These memories in turn
may unlock surrounding memories, the ‘flashbulb’ effect. Continuing to chal-
lenge cognitive functions preserves them. Education and ‘exercising the brain’ are
protective and lessen the rate of decline.9 Cholinesterase inhibitors may improve
memory in 25% and delay deterioration. Repetition, reassurance, and redirection
are necessary, and frustrating, tasks for carers.
Communication
Communication difficulties become increasingly problematic. Receptive
impairments (attention, comprehension, agnosia), expressive troubles (apraxia,
aphasia, dysarthria) and interpersonal stressors (disinterest, apathy, depression)
compound management. Language is eroded, health workers increasingly com-
municate with the carer and not the patient, and the focus of emotional support
shifts towards the caregivers. Providing functional spectacles and hearing aids,
and proper dental care should not be neglected.
Advance directives
Living wills or advance directives are infrequently executed and often lacking in
specific detail with respect to management of a particular illness, particularly if
that disease is dementia. They need to include such issues as safety to live alone
or drive, wandering, medication options for agitation, and the management of
feeding difficulties. When written, the nature of the terminal disease and the
natural history were probably not known. In emergency situations medical staff
are likely to proceed as they deem necessary to save life. Medical circumstances
are in a state of continual flux. Living wills are static documents and are gener-
ally unable to accommodate the dynamic changes of disease and the emotional
responses to it. Over time, and with advancing age (and organicity), there is a
tendency to moderate the aggressiveness of stated care wishes, which empha-
sises the requirement for frequent reviews and revisions.25 A feature of disease
to the nervous system is organic denial. As degeneration of the CNS proceeds,
the will to live, or the reluctance to appreciate the deterioration of quality of
life, strengthens. The patient may come to contest their own advance directive,
made when more competent. The major attribute of advance directives is that the
process involves communication and discussion of the medical issues between
patient, family and health professionals. These negotiations need to occur early
in the course of a dementing illness before competency is threatened. They are
based on the concept of respect for autonomy and on the patient’s right to self-
determination. These egocentric views of individual rights have been challenged
in non-Western cultures in which family and community interests may prevail.
The potential advantages of advance care planning, the avoiding of both under-
treatment and overtreatment, both for patient and doctor, are worthy. Creating
a robust and flexible document is, however, difficult.
Competence
Competent adults, capable of making decisions, have legally protected rights to
self-determination and having their choices about health respected. All adults
can be presumed to have capacity. Dementia challenges capacity. Capacity
refers to the making of a particular decision, such as the treatment refusal (see
Box 12.1).26 Capacity does not necessarily imply rationality; it can fluctuate but
at a point of time it is either present or absent, and it may differ in respect to
differing decisions needing to be made. The precise legal frameworks around
capacity or competence vary among countries and jurisdictions. If a person does
not possess capacity, decisions must be taken in that person’s best interests and
in the least restrictive manner possible. Medicolegal advice is often advisable.
At some stage during the course of dementia, competency to make personal

decisions about possible treatment options, to make an advance directive, or to
hold testamentary capacity is lost. Whether or not the proposed intervention
is in the person’s best interests is required to be made by another. The right of
informed consent is transferred to a legally authorised surrogate decision-maker
to exercise, on the patient’s behalf, healthcare decisions. The legal criteria con-
cerning Enduring Power of Attorney vary across jurisdictions. The surrogate,
preferably a close relation, is required to follow the explicit and implicit prefer-
ences of the patient. Organising this person early, and discussing with them
possible disease and decision scenarios, is very helpful. Surrogacy can be a lonely
task.27 Intrafamily relationships are invariably complex. Empirical studies sug-
gest that substituted judgements are erroneous in approximately one-third of
attempts.28 Particularly when making decisions about end of life, the surrogate
tends to be conservative and choose life, rather than being the ‘executioner’.
Authorising life-prolonging treatments for a parent or relative is generally the
easier option. Yet it is usually tinged with ambivalence for the necessary tests
and treatments are often unpleasant or even painful for the uncomprehending
older person.
BOX 12.1 Requirements to have capacity (Mental Capacity Act 2005, s 3)26
1 Understand information relevant to a decision, including reasonable

foreseeable consequences of a particular decision or of failing to make a
decision.
2 Retain the information, even for only a short time.
3 Use or weigh that information as part of the decision-making process.
4 Communicate the decision by any means.
Management of behavioural/psychiatric symptoms of dementia

BPSDs are responsible for many of the management problems relating to the
care of dementia patients, increased caregiver stress and increased rates of insti-
tutionalisation. They occur in up to 80% of patients, usually in the mid to late
stages of disease (see Table 12.3).
Agitation
Agitation is common. Anxiety is often expressed as agitation. Agitation refers to
inappropriate verbal, vocal or motor activity that is not judged by an outsider to
result directly from the needs or confusion of the patient. It may be a behavioural
response to pain, irritation, frustration, oversedation, boredom, loneliness, sen-
sory overstimulation, or invasion of personal space and privacy (particularly in
TABLE 12.3 Behavioural and psychiatric symptoms of dementia
Psychiatric symptoms Behavioural symptoms

Depression (up to 80%) Personality changes (up to 90%)
Delusions (20–73%) Agitation, restlessness (60%)
Misidentification (23–50%) Aggression (20–50%)
Anxiety (12–50%) Catastrophic reactions
Hallucinations (15–49%) Wandering, shadowing
Mania (3–15%) Screaming
Hoarding
Culturally inappropriate behaviours
Cursing
the apathetic patient). Attending to the source relieves the clinical sign. Sensory
interventions (such as aromatherapy, thermal bath, calming music, hand mas-
sage) have been shown to be the most effective non-pharmacological intervention
for agitation.29 Social contact, activities, environmental modification, caregiver
training and behavioural interventions appear less effective.29 Pharmacological
interventions are commonly, probably too frequently, trialled, with 20–30% of
residents in long-term care being prescribed antipsychotics or benzodiazepines,
10–30% antidepressants and 30% receiving cholinesterase inhibitors.30 There is
little convincing evidence of effectiveness of typical antipsychotics. Haloperidol
(0.5–6 mg daily) may reduce aggression but not agitation.31 Neurological effects,
falls and a possible acceleration of cognitive decline are adverse reactions of these
drugs. Atypical neuroleptics (risperidone, olanzapine) have a good evidence base
for effectiveness in behavioural symptoms,32 but the threefold increased cardio-
vascular risk may preclude their use, or at least this needs to be incorporated
into the risk–benefit equation.33 The efficacy of anticonvulsants is suggestive
but not conclusive. Cholinesterase inhibitors are possibly helpful.34 Memantine,
a NMDA-receptor antagonist, shows promise. Antidepressants are indicated if
affective symptoms contribute. High-dose vitamin E and oestrogens may be of
value. Benzodiazepine studies from the 1960s showed benefit, but concerns of
disinhibition limit their use (see Chapter 2). Placebo responses of 30% suggest
that the staff attention shown, and the associated interactions, are modestly
therapeutic. Training and support of staff in non-drug management strategies
reduces antipsychotic use by 20%.35
Wandering
Aimless walking, attempts to leave the environment (to go home), and shadow-
ing of caregivers are examples of this troublesome and potentially dangerous
symptom. Prevalence rates of 50% are reported, usually during the middle stages
of the disease. It is often as if the patient stays as physically active as their body
allows for they have a sense that soon this ability will be lost forever. This is a
major problem in Huntington’s disease patients in whom ataxia and falling are
additional significant risks. Structured recreational walks can reduce agitation in
wanderers.36 Collusion then redirection is the only management strategy likely
to contain this activity. Mild sedation can aggravate wandering.
Catastrophic reactions
Rage reactions, or brief periods of paralysing indecision and perplexity occur if
and when cognitive abilities are overwhelmed by external challenges. They may
be verbal and/or physical and associated with anxiety and panic. Limiting and
pacing cognitive demands reduces the frequency, and anxiolytic medication may
diminish the anxious response.
Depression
Depression occurs in at least 40% at some stage. This is often early in the course
and may not last even if untreated.37 Affective symptoms are common, though
severe depression is not, and suicidal ideation is reported in only 4%.38 Mood
symptoms tend to peak early in the course of dementia, whereas motivational
symptoms (avolition, social and emotional withdrawal) increase with the sever-
ity of dementia. There are surprisingly few treatment studies. TCAs are usually
not tolerable and SSRIs are preferred. Psychostimulants and cholinesterase
inhibitors warrant consideration, and ECT should not be easily dismissed as a
treatment option. Response rates, particular in VD, are often only modest.
Anxiety
Anxiety presents as agitation rather than psychic worry. It tends to fade as insight
diminishes. Anxiety contaminates psychometric testing. Caregiver anxieties
often increase as dementia advances.
Delusions
Misidentification, misplacement and forgetfulness provoke paranoia. Persecutory
and paranoid delusions are persistent in 20%. Antipsychotics do improve
20–30% of those experiencing delusions.
Hallucinations
Visual hallucinations are common in DLB and delirium, complicating dementia.
Sleep disorder
Insomnia, hypersomnia, delayed sleep phase syndrome and REM behavioural
sleep disorders are associated with dementing disorders (see Chapter 8). Bright
light therapy, similar to the treatment used in seasonal affective disorder, has
been shown to improve sleep in demented patients.39
Apathy and disinhibition

Frontal lobe dysfunction initially results in loss of behavioural control and aggres-
sion. With progression of disease, apathy increasingly dominates. Management
with behavioural and antipsychotic medications may mute the impulsive
responses. Psychostimulants deserve a trial in apathetic patients but there comes
a time when the dopamine receptors no longer have the capacity to respond.
Management of deficits of activities of daily living

Occupational difficulties created by the gradual onset of dementia are invariably
difficult and distressing for all concerned. Handling money, driving, using the
telephone, dressing, feeding and eventually toileting difficulties are the typical
array of daily living tasks that become problematic. Safety concerns become
relevant – access to smoking materials, medicines and poisons, electrical appli-
ances, dangerous stairs and roads all necessitate supervision and monitoring.
Generally, there is a long period of disabling symptoms and marginal self-care.
The management decisions that are required to be made during the course of
dementia are symptomatic of the crisis of modern medicine. That is, because an
intervention is technically possible, it must be offered. Nature’s decision-making
ultimately can’t be defied by modern medicine, though the journey can be made
tortuous by it.
Nutrition
In the final stages of dementia weight loss and loss of muscle and muscle
strength becomes apparent.4 This may be caused by cachexia, starvation and/
or the increasing difficulties of feeding. Eating difficulties develop as dementia
progresses. Apraxia complicates the mechanical task of eating, coexistent depres-
sion destroys appetite, bulbar involvement impairs swallowing, olfaction and
taste changes dissuade appetite, and hunger may not be able to be perceived.
Hand feeding, antidepressant medication and a fluid diet respectively may assist.
There is no evidence that long-term feeding tubes are beneficial in individu-
als with advanced dementia.40 They increase the risk of aspiration and they do
(partially) deprive the patient of the pleasure of eating and the companionship
of sharing food.
Hydration
It is claimed dying of dehydration is not unpleasant and that good mouth
care and sips of fluid provide adequate symptom control.41,42 Severe dehydra-
tion may contribute to delirium and this is the most persuasive indication for
hypodermoclysis.
Resuscitation
Cardiopulmonary resuscitation (CPR) in demented persons is medically futile.
While it may be the default position unless clearly documented to the contrary,
the success rate is similar to that found in persons with metastatic cancer.4 CPR
may be harmful and is undignified. Only 1% of demented residents in a nursing
home suffering cardiac arrest can be expected to be discharged alive from hospi-
tal.2 The dilemma for the clinician is that of discussing ‘do not resuscitate’ orders.
At what stage in the course of dementia does CPR become a futile intervention?
Place of care
New unfamiliar and frightening environments, such as hospitals, and the medi-
cal risks of interventions need to be considered and weighed against the potential
benefits. Emergency departments and hospitals expose the demented to serious
risk.2 Enhanced palliative expertise provided to residential care facilities may in
the future allow these persons to continue to live and die in their ‘homes’.
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13 Mitchell SL, Kiely DK, Hamel MB. Dying with dementia in the nursing home. Arch
Intern Med. 2004; 164: 321–6.
14 Aminoff BZ, Adunsky A. Dying dementia patients: too much suffering, too little pal-
liation. Am J Alzheimers Dis Other Demen. 2004; 19: 243–7.
15 Larson EB, Shadlen MF, Wang L, et al. Survival after initial diagnosis of Alzheimer’s
disease. Ann Intern Med. 2004; 140: 501–9.
16 Hurley AC, Volicer B, Mahony MA, et al. Palliative fever management in Alzheimer
patients: quality plus fiscal responsibility. Adv Nurs Sci. 1993; 16: 21–32.
17 van der Steen JT, Ooms ME, van der Wal G, et al. Pneumonia: the demented patient’s
best friend? Discomfort after starting or withholding antibiotic treatment. J Am Geriatr
Soc. 2002; 50: 1681–8.
18 Sutherland T, Hill JL, Mellow BA, et al. Clock drawing in Alzheimer’s disease: a novel
measure of dementia severity. J Am Geriatr Soc. 1989; 37: 719–25.
19 Manos PJ. The utility of the ten-point clock test as a screen for cognitive impairment
in general hospital patients. Gen Hosp Psychiatry. 1997; 19: 439–44.
20 Duff Canning SJ, Leach L, Stuss D, et al. Diagnostic utility of abbreviated fluency meas-
ures in Alzheimer’s disease and vascular dementia. Neurology. 2004; 62: 556–62.
21 Keady J, Nolan M. Younger onset dementia: developing a longitudinal model as a basis
for a research agenda and as a guide to interventions with sufferers and carers. J Adv
Nurs. 1994; 19: 659–69.
22 Kitwood T. The dialectics of dementia: with particular reference to Alzheimer’s disease.
Aging Soc. 1990; 10: 177–96.
23 Sweeting H, Gilhooly M. Dementia and the phenomenon of social death. Sociol Health
Illn. 1997; 19: 93–117.
24 Williams DDR, Garner J. People with dementia can remember. Br J Psychiatry. 1998;
172: 379–80.
25 Wittink M, Morales K, Meoni LA, et al. Stability of preferences for end-of-life treatment
after 3 years follow-up. Arch Int Med. 2008; 168: 2125–30.
26 General Medical Council. Good medical practice: duties of a doctor. London: GMC;
2006.
27 Bernat JL. Informed consent. In: Voltz R, Bernat JL, Borasio GD, et al., editors. Palliative
28 Sulmasy DP, Terry PB, Weisman CS, et al. The accuracy of substituted judgements in
patients with terminal diagnoses. Ann Intern Med. 1998; 128: 621–9.
29 Kong EH, Evans LK, Guevara JP. Nonpharmacological interventions for agitation in
dementia: a systematic review and meta-analysis. Aging Ment Health. 2009; 13: 512–20.
30 Conn DK, Seitz DP. Advances in the treatment of psychiatric disorders in long-term
care homes. Curr Opin Psychiatry. 2010; 23: 516–21.
31 Lonergan E. Haloperidol for agitation in dementia. Cochrane Database Syst Rev. 2001;
4: CD002852.
32 Curran S, Turner D, Musa S, et al. Psychotropic drug use in older people with mental
illness with particular reference to antipsychotics: a systematic study of tolerability and
use in different diagnostic groups. Int J Geriatr Psychiatry. 2005; 20: 1–6.
33 Keys MA, De Wald C. Clinical perspective on choice of atypical antipsychotics in eld-
erly patients with dementia, part II. Ann Long Term Care. 2005; 13: 30–8.
34 Wynn ZJ, Cummings JL. Cholinesterase inhibitor therapies and neuropsychiatric
manifestations of Alzheimer’s disease. Dement Geriatr Cogn Disord. 2004; 17: 100–8.
35 Fossey J, Ballard C, Juszczak E, et al. Effect of enhanced psychosocial care on antipsy-
chotic use in nursing home residents with severe dementia: cluster randomised trial.
BMJ. 2006; 332: 756–61.
36 Aronstein Z, Olsen R, Schulman E. The nursing assistants’ use of recreational inter-
ventions for behavioural management of residents with Alzheimer’s disease. Am J
Alzheimer’s Other Demen. 1996; 11: 26–31.
37 Brodarty H, Luscombe G. Studies on affective symptoms and disorders: depression in
persons with dementia. Int Psychogeriatr. 1996; 8: 609–22.
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patients: the role of depression. Age Aging. 1998; 27: 503–7.
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for managing behavioural problems (Editorial). BMJ. 2002; 325: 1312–13.
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dementia. Cochrane Database Syst Rev. 2009; 2: CD007209.
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end of life: legal and ethical considerations. Death Stud. 2000; 24: 233–54.
42 Twycross R, Lichter I. The terminal phase. In: Doyle D, Hanks GWC, MacDonald N,
editors. Oxford Textbook of Palliative Medicine. 2nd ed. Oxford: Oxford University
Press; 1998. p. 500.
CHAPTER 13
Terminal neurological disorders
I am not only a skeleton but a badly articulated one to boot. If to this is

coupled the fact of the creeping paralysis, you have the complete horror.
WNP Barbellion (1889–1919)1
The typical course of these illnesses may be at least one to two decades.
Determining the terminal phase can be uncertain. Death is sometimes even-
tually rather unexpected (and often in hospital).2 The shift from an acute
interventional medical model, necessary to preserve quality of life, to allowing
a terminal decline is often clinically a passive process. Robust discussions early
in the course of disease, prior to any loss of capacity, concerning management
options late in the illness may achieve decisions in the patient’s best interests.2 A
palliative approach, including advance care planning, should be introduced early
in those with neurodegenerative disorders. Often the terminal event is an acute
episode of sepsis. Respiratory, gut and skin problems are undoubted issues in the
final phases of these patients’ lives, but troublesome neuropsychiatric symptoms
present major management challenges. Dying is difficult, dying with an already
compromised nervous system is very difficult.
PARKINSON’S DISEASE
Since the discovery of levodopa in the 1960s the treatment of Parkinson’s disease
(PD) has been revolutionised.3 Approximately 10% of PD patients present before
the age of 50 years and can live well for 20–30 years with modern treatments.
The disease in older onset patients tends to have a less favourable course. Within
5–10 years, problems with drug unresponsiveness, dyskinesias, dementia and
depression compound management.2 Persons with Parkinson’s disease become
psychologically very attached to their medication and complex medication
regimes.2 Alterations require careful consideration, negotiation and a willingness
to reconsider. The terminal phase may last 1–2 years.2
187
Anxiety and depression

Movement is the fundamental nervous system function. For it to be slowed
(bradykinesia) and inefficienct is a primal wound to any organism. Anxiety
is a consequence. To be frozen in movement is an innate fear. A state of utter
helplessness ensues. This brief moment of ‘death’ may induce unease, panic and
even PTSD. In patients with on–off fluctuations, anxiety is more often related
to the off phase. Anxiety is higher if mobility is less.4 Depression may be pre-
cipitated during the latter phases of PD, particularly if other risk factors are
present. Differentiating psychomotor retardation and bradykinesia is difficult.
Depression, probably an integral part of the disease, occurs in more than 40%.4
Anxiety tends to be a prominent feature of this depression. Depression is com-
moner in those with more severe cognitive impairments and a past affective
history. Apathy and depression may coexist. Depression is a risk factor for PD,
and may be the presenting symptom.4 Suicide and alcoholism rates in PD are
low. SSRIs are the most tolerable antidepressant choice. Tricylics’ anticholinergic
properties potentiate the risk of delirium but may have a mild anti-parkinsonian
action. The response rates in ‘organic’ depressions are often disappointing. ECT
should not be discounted, and it has the added advantage of improving motor
symptoms as well as mood.5
Dementia
Dementia complicates at least 30% of PD, particularly in the elderly.4 In the
majority, Lewy bodies are present. Bradyphrenia, the slowing of cognitive proc-
esses, is a feature. With progression, apathy and abulia become increasingly
evident. Cholinerasterase inhibitors warrant a trial.
Psychosis and complications of dopaminergic therapy

Psychosis occurs in approximately 30% and is usually caused by levodopa
therapy in younger patients.4 In the elderly it may indicate the emergence of
dementia, which further lowers the threshold to tolerate dopamine agonist
therapy. Hallucinations and illusions are mainly visual, occasionally tactile
and olfactory. These sensory aberrations are often fleeting. Fluctuating per-
secutory and paranoid delusions often accompany them. Delirium needs to
be excluded and the dose of antiparkinsonian medication reduced if possible.
Meticulous drug fine-tuning does not invariably result in easing the adverse
effects. Antipsychotic medications risk aggravating the movement disorder. The
newer atypical neuroleptics are preferred. Low-dosage quetiapine or olanzapine
are usually tolerated with only minimal neurological adverse reactions. The most
effective and safest medication is clozapine, though sedation may be problematic.
The required doses are generally very low (15–50 mg/day), but there is a risk of
blood dyscrasia. Tremor may also be improved with clozapine. Ondansetron has
TERMINAL NEUROLOGICAL DISORDERS 189
been trialled for this indication, and in dementia cholinesterase inhibitors may
be an alternative to antipsychotic medication.3 Neurosurgery and deep brain
stimulation may be indicated, a reflection of the enormity of the distress these
medication adverse effects may create. Less distressing and equally embarrassing
are the array of motor fluctuations, dyskinesia, akathisia, hyperkinesia, dysto-
nia and chorea that may occur at various dosing intervals. These patients are
generally extremely reluctant to reduce their dopamine dose even fractionally,
appearing to be addicted to them.3 Hypersexuality is occasionally a problem.
Partners are very unlikely to volunteer this information without prompting.
Erectile failure is a more common symptom in PD. Excessive gambling and
punding (repetitive, purposeless, stereotyped behaviours) are possible risks of
dopaminergic medications.
Pain
Stiffness and rigidity caused by PD can be uncomfortable.3 Pain is common,
reported by nearly half of patients with PD.5 Pain types include musculoskeletal
(44%), pain secondary to dystonia and dyskinesia (19%), central pain (13%),
and neuropathic pain (11%).6 Antispasmodic medications, local botulinum
toxin injections and adjustment of the dopaminergic regime may be indicated.
Intermittent apomorphine can be useful.7 Constipation is inevitably a problem
due to poor gut mobility. If opioids are introduced, a laxative regime is necessary.
If opioids induce nausea, domperidone is the anti-emetic of choice as it does not
cross the blood–brain barrier.
Sleep disturbance
Sleep is fragmented in PD. Dopaminergic medications induce vivid dreams,
often precursers to a psychosis. REM behavioural disorders are more frequent.
Restless legs at night can be disruptive and painful. Though it is usually treated
with dopamine agonists, clonazepam and opioids do often provide some respite.
Daytime sleepiness is a consequence of the night-time disruptions.
Terminal Parkinson’s disease

If there is bulbar involvement, chest infections may be the eventual cause of
death. Akinetic rigidity is the usual preterminal motor state. During the ter-
minal phase, oral compliance may be compromised. Apomorphine infusions
may be useful at this stage at doses of up to 50 mg/24 hours. Very low dosage
(8–10 mg/24 hours) may be sufficient.8 Pretreatment with rectal domperidone
is preferable as nausea is a major adverse effect of apomorphine.7,8 Nasogastric
dispersible co-beneldopa or the topical dopamine agonist rotigotine are pos-
sible options at this stage.2 Parenteral anticholineric agents severely aggravate
delirium, but are an option if the patient is sedated. Abulia, an impairment of
will, or an inability to initiate behaviour and actions (including speech, creating

akinetic mutism), is a possible complication of late-stage PD. The phasing out
of the dopamine agonists account for this, and apomorphine warrants a trial for
this distressing symptom.
MULTIPLE SCLEROSIS
In multiple sclerosis (MS), inflammatory focal demyelination of the nervous
system causes a myriad of sensory, motor and neuropsychiatric symptoms. The
natural course of the disease is extremely variable. The disease burden accumu-
lates for the majority, and after 2–3 decades a progressive deteriorating course is
assumed. Irreversible neurological deficits create physical dependency and psy-
chiatric morbidity.9 Overall life expectancy is 7 years less than normal. Mortality
increases with disability. Infection is the most common cause of death.10 There
is no cure for MS. Disease-modifying agents, such as interferons and glatiramer,
may influence the natural course. This for most is subtle, and may merely prolong
the duration rather than the quality of life.
Psychological adjustment is made most difficult, for symptoms wax and wane.
They are unpredictable, embarrassing and invisible. They erode physical and
psychological autonomy. The inevitable march of MS undermines individuals
and families.11 Fatigue is a core disabling feature, present in up to 74% and often
described as the most disabling symptom.12 Modafinil may be useful particularly
if the fatigue is associated with daytime sleepiness.13 The lifetime prevalence
of depression is 40–60% and is related to cerebral involvement of the disease,
though this is not clearly correlated with MRI scan lesion load.9 Disruption of
frontal-temporal circuits by plaques may be the critical organic risk factor for
depression, as well as for bipolar mood disorders which have a twofold increased
incidence. There are generally a host of psychosocial adversities further enhanc-
ing the risk of affective disorder. Suicide rates are elevated 7.5-fold, especially
in the young.10 Interferon medications can induce depression. Antidepressant
medications are of benefit in MS depression.12 SSRIs are likely to be the most
tolerable antidepressants. Persons with already compromised CNS functioning
detest any further loss in function such as that induced by psychotropic medica-
tion adverse effects.11
Eutonia, euphoria, pathological laughing/crying and lability of mood may
respond to cognitive and distracting strategies and low-dose antidepressants.14
They occur in 10–25% of MS patients, usually in those more severely affected.
Cognitive impairments occur in 40–60% and are severe in 21–33%.9 The
dementia is ‘subcortical’, the deficits being a slowing of cognitive processing,
impaired auditory attention, memory retrieval difficulties and executive function
impairments. Language and memory are not manifestly impaired. The demen-
tia of MS is easily missed at the bedside, yet hinders daily living significantly.
Superimposed depression may amplify these cognitive deficits.12 The impact on

employment, tasks of daily living and competency is considerable. Management
options are limited. Recognition allows the possibility of others assisting in com-
pensating for the deficits. Cognitive retraining and memory cues may help in
the early stages. If associated with a significant neurological relapse, high-dose
corticosteroids may warrant a short course. Cognitive enhancing medications
such as the cholinesterase inhibitors, and psychostimulants have been trialled
with uncertain success.12 Personality change, particularly apathy, irritability and
disinhibition, are subtle indicators of the slow organic disintegration of MS,
rather than being intentional ‘attention-seeking’ behaviours.
Pain is a frequent complication, and is often neuropathic in character.
Musculoskeletal pain from immobility and spasm may further erode quality of
life. Cannabinoids may have a modest effect of the pain from spasm and central
pain.12
By the time of death, the person who developed MS decades previously is,
sadly, hardly recognisable. Bedbound and cognitively a shadow of their prior self,
the patient in the frail terminal physical state may be best humanely, not actively,
treated. MS itself is rarely a direct cause of death.
STROKE
Stroke is a heterogeneous group of diseases which include brain infarction,
intracerebral bleeding, subarachnoid haemorrhage and rare entities such as
vasculitis and vessel dissections. About 20% die within one month of a stroke,
and 10% in the following year, so within 2 years one-third have died.15 Many
deaths are sudden, caused by acute progression of the strokes. Only one-quarter
fully recover, and 40–50% experience some form of disability.16 Stroke units,
thrombolysis and lifestyle education may improve prognosis and prevent stroke,
but the ageing population is likely to increase the rates over subsequent decades.
There is an enlarging population of severely disabled, dependent survivors who
have psychiatric and palliative needs. Additionally, 15% of cancer patients have
cerebrovascular lesions at autopsy, and 50% of these lesions might have been
symptomatic.17
Acute stroke results in ‘modified mental processing’.18 Difficulties with
remembering the event and anosognosia (and denial) influence judgement
and decision-making. Emotional incontinence, sadness, mild disinhibition,
catastrophic reactions and anxiety over the first few weeks suggest depression,
and may be eased by low-dosage antidepressants. These acute psychological
wounds tend to settle over time. Weeks to months later, post-stroke depression
may evolve in up to 40%, of which 25% is major depression.18 Guilt, hopeless-
ness and suicidal ideation tend not to be prominent depressive features. Mood
lability and rehabilitation inertia dominate. Coexistent depression amplifies
cognitive impairments. The location of the stroke is a minor risk factor for
depression compared with severity, functional outcome and cognitive damage.18
Assertive antidepressant trials are indicated. In addition to treating and prevent-
ing mood dysfunction, antidepressants improve cognitive and motor recovery
and reduce mortality.19,20 The earlier literature advocated nortriptyline, but the
critical influence to choice is tolerability. Most use SSRIs as first choice. Fatigue
(independent of depression) haunts rehabilitation. Psychostimulants can be
of benefit, though usually pacing activities and demands is more therapeuti-
cally enduring. Stroke patients with limited cerebral reserves are at high risk of
delirium. Communication difficulties, particularly with left-sided lesions, are a
crucial challenge of management. This is made especially difficult if there is also
cognitive impairment (which is highly likely). Memory, spatial awareness and
personality may all be affected. Post-stroke dementia occurs in 20–25%. Pain is
a prominent problem post-stroke, often within weeks. The ‘shoulder-hand syn-
drome’, headache and ‘central post-stroke pain’ are difficult conditions to treat.
Aphasic patients have been shown to receive less analgesia.21
The devastating consequences of stroke not only affect the patient. The bur-
den of care on others is immense. The rates of depression in carers are high.
Short respite admissions are valuable, and also provide an opportunity to review
changing care needs. Bereavement support can easily be instituted at this time,
and better prepares both patient and relatives for the uncertain future ahead.
AIDS
HIV-positive status has immense impact on relationships, family, occupation
and society. HIV is a potent neurotoxic agent and enters the CNS early in the
course of illness. HAART therapy, if available, has radically altered the neuropsy-
chiatric complications.
Adjustment issues are liable to be influenced not only by the personal circum-
stances of the patient but also by the characteristics of the society they live in. Drug
abuse, impoverished socioeconomic circumstances, lifestyle and social stigma
may be relevant influences. Fatigue is an invariable complaint. Neuropathic
pain may complicate in about 30–50%.22 Pain management in the drug-using
HIV-positive patient is challenging (see Chapter 14). Major depressive disorder
and the elevated risk of suicide deserve appropriate interventions. Suicide risk
may be enhanced by impulsive behaviour and emotional lability, though most
suicides occur early in the disease. Acute manic episodes may be indicative of
early dementia, as mania is usually associated with cognitive impairments. The
abrupt presentation of psychotic symptoms should be clinically considered to
be an infective delirium until this has been excluded. Psychosis tends to her-
ald dementia. Subtle personality and cognitive changes may occur early and
potentially influence adjustment processes, decision-making and compliance
with medications. Interruptions of medication compliance are liable not only to

risk progression and complications, but subsequent re-introduction may prove
ineffective. Cognitive impairment is present in 20–30% of those who are not on
HAART therapy. The advent of HAART and longer survival are factors actually
increasing the prevalence of cognitive impairment and AIDS dementia complex
(ADC), but perhaps reducing its severity. The prevalence of HIV dementia is
approximately 13%. The incidence of AIDS dementia has halved post-HAART
from 7% per year to 3% per year, but the prevalence has doubled because of the
increased survival.22,23 HAART provides only partial protection from the neu-
rotoxicity of HIV. HAART is changing the typical neuropsychological features
either directly or by delaying presentation to an older age group and thus add-
ing other risk factors for dementia. ADC is not an inevitable consequence of
HIV infection and nor is it always progressive.23 ADC is subcortical dementia
with cognitive, motor and behavioural symptoms (see Table 13.1). Insight can
be preserved until late.23 Differentiation from depression can be difficult, and
therapeutic trials of SSRIs and psychostimulants are not to be dismissed. ADC
is a clinical diagnosis and many decline formal neuropsychological evaluation,
for this merely highlights the deficits and provides no therapeutic advantage.
Deficits able to be recognised by the self, such as memory impairment and
psychomotor coordination, increase the desire for death, whereas executive
dysfunction and abstract reasoning difficulties do not.24
TABLE 13.1 Clinical features of AIDS dementia complex (ADC)23
Early Late
Cognitive Inattention Global dementia
Poor concentration
Forgetfulness
Slowed thinking
Motor Ataxia Paraparesis
Impaired handwriting Incontinence
Tremor
Urinary urgency/hesitancy
Impaired rapid alternating
movements
Abnormal reflexes
Leg weakness
Behavioural Social withdrawal Mutism
Apathy
Irritability/mania
The profound neurological sensitivity to antipsychotic medications limits use.

Clozapine, the most effective of the antipsychotic medications also has the
fewest neurological side effects. Benzodiazepines are well tolerated but sedative
at higher dose. Antiretroviral medications, particularly those that penetrate the
CNS and are used in combination, may cause insomnia and depression in less
than 10%. Antiretroviral agents may interact with psychotropic medications.
Neuroprotective agents such as memantine and selegiline may have a role.
The clinical course of AIDS is erratic and difficult to predict, even with
good medication compliance. A major clinical dilemma in the terminal phase
is whether or not antiviral and prophylactic antibiotic medications are con-
tinued or not. Risking terminal opportunist infection is not necessarily wise,
as uncontrolled symptoms such as diarrhoea may cause a very prolonged and
uncomfortable death.25 Very assertive medical care is generally required to pro-
tect quality of life, and withdrawing this towards the expected end of life can be
problematic. Orchestrating a ‘good death’ in AIDS patients may not be possible.
Early in the course of the epidemic, palliative care institutions were sometimes
available for these patients. In countries with access to newer therapies the ill-
ness has been transformed into a manageable chronic illness, and the supportive
phase may last decades.25 The mean time from diagnosis to death has increased
from 6 months to over 48 months.23 If accumulated neurocognitive deficits
enforce institutional care for the long-term survivors, then palliative medicine’s
role is likely to be required again. Death in AIDS is often stigmatised.26 It may
be embarrassing to the family and secretive; customary bereavement rituals may
not be performed. The burden of shame complicates grieving.
AMYOTROPIC LATERAL SCLEROSIS/MOTOR NEURONE DISEASE (ALS/

MND)
No cure is known for ALS/MND. It most commonly presents in the sixth decade
and has a prognosis of 3–4 years for most, though rarely it may be longer.27 Most
commonly it is sporadic with familial ALS/MND representing only 5–10% of
cases. Fronto-temporal executive dysfunction may precede or follow bulbar, limb
or respiratory muscular weakness.28 Bulbar ALS/MND, which occurs in about
20% of those affected, tends to have a shorter clinical course than spinal presen-
tations. With the exception of the marginally effective riluzole, no treatment is
known. The reactive distress and profound weakness experienced and the seda-
tive adverse effects of antispasticity agents and anxiolytic medications can easily
mislead the clinician into thinking that depression is compounding the illness.
Major depressive disorder, in contrast to sadness and emotional distress, is actu-
ally a relatively uncommon result of ALS/MND, the rate being about 10–12%.28
Pseudobulbar affect (emotional lability and incontinence, pathological laugh-
ing/crying) is a feature in about 50%.29 This can be symptomatic of depression
and of dementia. It may be eased by (low-dose) antidepressants. SSRIs tend to

be preferred. While tricyclics may beneficially reduce drooling, they may also
thicken respiratory secretions and increase tenacity, as well as aggravating con-
stipation. Any clinical hint of depression deserves psychosocial and medication
intervention. Somewhat surprisingly ALS/MND patients generally maintain
good self-perceived quality of life, despite disease progression, provided their
social and spiritual concerns are met.28 Remarkable psychological resilience is
commonly observed. Physical function is not the major determinant of quality
of life in ALS/MND.28 Communication aids are critical to the quality of remain-
ing life. Assessment of cognitive functioning in ALS/MND patients is difficult
because of the communication struggles. Clinicians are reluctant to examine
cognition for it really just confronts the patient with the recognition of further
losses. There is an association between bulbar ALS/MND and frontotemporal
dementia (see Chapter 12). ALS/MND patients are wary of medications as they
are very protective of their remaining function and are reluctant to risk CNS side
effects. Swallowing problems are ultimately inevitable, and assisted feeding and
ventilation are issues that require consideration. They are not without benefi-
cial and adverse effects. Pain caused by spasm, cramps and immobility requires
physiotherapy and analgesic medication. With advancing weakness and physical
dependency, anxiety about the process of death becomes a preoccupying concern
for many. Benzodiazepines and opioids may be helpful for respiratory distress
and the associated panic. Perhaps up to 20% of ALS/MND patients wish for a
hastened death, this being more likely in those depressed, hopeless and without
religious faith.28 Suffocation and ‘choking to death’ are actually rare, 90% dying
in their sleep as a result of increasing hypercapnia.30 Rapidly progressive respira-
tory failure is the usual terminal event. Though often in the management plan,
the need for continuous deep sedation is unusual in practice.
MUSCULAR DYSTROPHY
These predominantly genetic disorders result in early death. The commonest,
Duchenne’s muscular dystrophy (DMD), is an X-linked recessive trait, occurring
predominantly in males, affecting pelvic and pectoral musculature but sparing
smooth and bulbar musculature.31 Death by respiratory failure and infection
usually has occurred by the age of 25 years.31 Mild intellectual impairment has
been associated with DMD. Because of difficulties clinically ascertaining cogni-
tion and mental status, the neuropsychiatric aspects of these diseases are less
established. The implication of muscle weakness and wasting on an adolescent,
the developmental phase most sensitive to body image conflicts and self-esteem
doubts, is obviously massive. The family, who experience genetic guilt and anger,
tend to focus their care in purely physical ways by concentrating, often exclu-
sively, on signs of progress and (begrudgingly) deterioration. The stress of the
family unit is massive. More than one child may be affected. Marital discord is
common, divorce being reported in up to 24%.32 Such high rates of marital disil-
lusion are typical of relationships that suffer child loss. The course of disease is
usually about a decade. Management decisions such as those relating to assisted
ventilation are not infrequently made during an emergency. Rarely can these
individuals and families proactively come to such decisions. Professionally one
seems helpless, unable to infiltrate the often very firm defences these families
use for protection. Issues of fears of choking, ventilatory panic and relating to
ongoing ventilation quandaries (both for patient and carers) are sometimes the
first opportunity for palliative and psychosocial interventions. Explanation,
reassurance, benzodiazepines for anxiety, and opioids for respiratory distress,
may ease the terminal phase.
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19 Jorge RE, Acion L, Moser D, et al. Escitalopram and enhancement of cognitive recovery
following stroke. Arch Gen Psychiatry. 2010; 67: 187–9.
20 Chollet F, Tardy J, Albucher JF, et al. Fluoxetine in motor recovery after acute ischae-
mic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011; 10:
123–30.
21 Kehayia E, Korner-Bitensky N, Singer F, et al. Differences in pain medication use in
stroke patients with aphasia and without aphasia. Stroke. 1997; 28: 1867–70.
22 McArthur JC. HIV dementia: an evolving disease. J Neuroimmunol. 2004; 157: 3–10.
23 Brew BJ. HAART in AIDS dementia complex and palliative care. Prog Palliat Care.
2004; 12: 171–7.
24 Pessin H, Rosenfeld B, Burton L, et al. The role of cognitive impairment in desire for
hastened death: a study of patients with advanced AIDS. Gen Hosp Psychiatry. 2003;
25: 194–9.
25 Maddocks I, Brew B, Waddy H, Williams I. Palliative Neurology. Cambridge: Cambridge
26 Chandra PS, Deepthivarma S, Manjula V. Disclosure of HIV infection in south India:
patterns, reasons and reactions. AIDS Care. 2003; 15: 207–15.
27 Oliver D, GD Borasio. Diseases of motor nerves. In: Voltz R, Bernat JL, Borasio GD,
et al., editors. Palliative Care in Neurology. Oxford: Oxford University Press; 2004.
pp. 79–89.
28 Norris L, Que G, Bayat E. Psychiatric aspects of amyotrophic lateral sclerosis (ALS).
Curr Psychiatric Rep. 2010; 12: 239–45.
29 Abrahams S, Goldstein LH, Kew JJM, et al. Frontal lobe dysfunction in amyotrophic
lateral sclerosis: a PET study. Brain. 1996; 119: 2105–20.
30 McDermott CJ, Shaw PJ. Diagnosis and management of motor neurone disease. BMJ.
2008; 336: 658–62.
31 Maddocks I, Stern L. Muscular dystrophy and related myopathies. In: Voltz R, Bernat
Press; 2004. pp. 90–6.
32 Buchanan D, LaBarbera C, Roelofs B, et al. Reactions of families to children with
Duchenne muscular dystrophy. Gen Hosp Psychiatry. 1979; 1: 262–8.
CHAPTER 14
Chronic mental illness and dying
I feel, sirs, that I am rapidly dying . . . I was mad, but I am sane now.
Cervantes, Don Quixote (1604–05)1
Chronic mental disorders may be fatal conditions. The natural history of these
diseases, poor adherence to treatment regimes, metabolic adverse effects of
medications, self-neglect, the perils of homelessness, substance abuse, violence
and suicide may limit quality and quantity of life. The life expectancy of a person
suffering schizophrenia is 10 years shorter than expected for the general popu-
lation.2 Those who suffer mental disorders can also experience life-threatening
and terminal illnesses. Medical comorbidity, of all types, is associated with seri-
ous psychiatric illness. Approximately 50% of psychiatric patients have known
medical conditions, and 35% have undetected medical conditions.2 The emerg-
ing epidemic of diabetes in the general population, and more particularly in the
mentally ill population exposed to atypical antipsychotic medications, accounts
for the two- to fourfold increase rate of diabetes in those with schizophrenia.3
Adults with chronic mental disorders have at least double the risk of dying from
natural causes at any age, compared with the general population.4
Most studies show a lower incidence of cancer in those with severe mental
illness.5 The heavy cigarette smoking which traditionally took place in mental
institutions would suggest that lung and pharyngeal cancer incidences should be
increased, though this appears not necessarily to be the case.5,6 There may be a
protective genetic factor in these patients,6 or alternatively antipsychotic medica-
tions may have an anticancer effect.5 There is a higher incidence of breast cancer
in women with psychiatric disorders which may be related to lower parity or per-
haps hyperprolactinaemia associated with antipsychotic medication.5 While the
rate of cancer among patients with schizophrenia (and severe mental illness) may
be reduced,5 the lethality of the cancer may be greater. The overall cancer mor-
tality in patients with schizophrenia is almost four times higher than that of the
199
general population.2 Cancer is the second leading cause of death, after suicide,
in schizophrenic persons.8 A low uptake of cancer screening, inequity of access
to treatment, diagnostic overshadowing (attributing psychogenicity to organic
symptoms), comorbidities such as obesity or malnutrition, drug interactions
between psychotropic and chemotherapy agents, chemotherapy aggravating
antipsychotic medication induced blood dyscrasias, the exacerbation of mental
symptoms consequent to the stressors of medical illness, non-compliance, and
difficulties maintaining a therapeutic alliance with the mentally sick are some of
the multitude of factors accounting for the increased lethality.5
There is a very limited literature on the palliative care needs or nature of care
provided to persons with severe persistent mental illness (SPMI).9 Individuals
with severe mental illness have limited opportunities to engage in discussions
about advance care planning.10 Fluctuating capacity, disorganisation, apathy and
our professional neglect of these issues may be relevant explanations, though
there is little shortage of medicolegal attention to preferences and permissions
with respect to the management of an individual’s psychiatric illness. It has
been shown that those with SPMI do have a substantial interest and an ability
to participate in advance care planning.11 When a terminal illness is diagnosed
the presumptions of the patient, relatives and carers are often not only that the
pre-existing psychiatric illness will be exacerbated, but also that the patient will
‘not cope’ and the medication regime ‘will need to be strengthened’. This is not
necessarily correct, despite their vulnerability. Many cope very well; for some
their mental condition actually improves, and others struggle desperately.
AFFECTIVE DISORDERS
The natural history of a depressive episode is for spontaneous resolution. This
generally occurs between 6 months and 10 years; however, predicting this
occurrence is not possible. Antidepressant medications merely palliate the
depressive symptoms, until this resolution occurs. Depression recurs in at least
50% of patients. With each recurrence, clinicians tend to maintain antidepres-
sant medication for longer periods, and after more than a few recurrences many
are advised to stay on a therapeutic dose of a tolerable and effective medication
indefinitely. Terminally ill patients who are taking an existing antidepressant
regime should be continued on this regime. The dosage may need to be reduced
if renal and hepatic functions deteriorate. Patients with a known history of prior
depression who experience a relapse during terminal illness should be recom-
menced on this previously effective antidepressant.
Spontaneous resolution of a depressive episode may occur during the course
of a terminal illness. Clinical impression suggests that this occurs not infre-
quently. Many historical psychiatric treatments involved physiologically and
psychologically ‘shocking’ the patient. Cold douching, violent rotation, fever
CHRONIC MENTAL ILLNESS AND DYING 201
therapy, and insulin and electrical convulsive therapies are such examples.12
Freud commented that melancholia may be brought to a temporary end by inter-
current organic disease.13 There is a number of case reports of such recoveries.1,14
This phenomenon is also commonly observed in the few days following a suicide
attempt. Transiently mood lifts, and occasionally it resolves. It is speculative as
to whether the mechanism is psychological or physiological.
Bipolar affective disorders present particular management difficulties in
palliative care. High-dosage corticosteroids (above 40 mg equivalent dose of
prednisone) can induce mood instability, particularly in those who are predis-
posed (see Chapter 11). This may take weeks to settle even with the cessation
of the steroid and antimanic medications. AIDS is particularly associated with
mania, and because of sensitivity to the neurological side effects of antipsychot-
ics, benzodiazepines and mood stabilisers may need to be relied upon in these
patients. Lithium carbonate remains the mood stabiliser of first choice for bipolar
illness. However, it has a narrow therapeutic range, and at toxic levels lithium
carbonate is dangerous. Acute delirium and neurological signs (tremor, parkin-
sonism) are clinical indicators of toxicity. Urgent serum levels must be obtained.
Fever, dehydration and renal impairment predispose to lithium toxicity. Ceasing
maintenance, lithium carbonate is associated with an increased incidence of
manic swings several months later. Lithium for many of these patients has been
very valuable, and they may be reluctant to cease it. Alternative mood stabilisers
such as sodium valproate, carbamazepine and lamotrigine, if tolerable, are not as
efficacious, and a terminal illness is not an occasion to trial alternatives. Lithium
carbonate should preferably be continued and reviewed very carefully (with
frequent serum monitoring). Benzodiazepines do possess antimanic properties,
and clonazepam can prove a safe and effective option.
There is no literature concerning the impact of a terminal illness upon chronic
dysthymia. Anecdotally the distractions of severe physical illness often redirect
anxiety and worry onto the patient’s oncological status. Adjustment issues and
oncological stressors may trigger reactive mood dips. It is as if the ongoing
health concerns validate the dysphoria and reinforce mental health invalidism.
Generally, antidepressants are prescribed as ‘cover’, though if therapeutic gains
can be made it is usually in response to psychosocial therapies. Unhappy people
are likely to die unhappy.
PSYCHOTIC DISORDERS
Delay of presentation of physical symptoms resulting in delayed diagnosis is a
particular concern in schizophrenia. Hidden fungating breast wounds, ignored
rectal bleeding and apparent insensitivity to pain make the detection of under-
lying malignancy more difficult in these patients, even if they are resident in
an institution. The lack of response to the emergence of physical symptoms is
multifactorial.15 Difficulties verbalising the symptoms, extraordinary tolerance

of discomfort and pain, fear of disclosure to medical and nursing staff with
whom they may have fraught relationships, anxieties about trusting others, the
incorporation of the ‘new’ symptom into their existing delusional system, and
the withdrawn negative symptoms of schizophrenia may all contribute.15,16 For
the attending psychiatrist it may be the distraction of focusing upon the primary
psychiatric illness, and minimising the physical symptoms, that contributes to
delayed recognition. Astute (junior) staff in psychiatric hospitals can and do
diagnose cancers and other serious medical illnesses early.
Management may be made easier for the patient if they have an existing
therapeutic relationship with an individual or a system. However, if paranoia
and trust issues are evident, management may be most difficult and sometimes
impossible. The reclusive elderly paraphrenic, the hostile and chaotic young
male who complicates a psychotic illness with substance abuse, and the apathetic
negativistic catatonic schizophrenic are clinical examples of such patients. Close
liaison with family and the attending psychiatric staff is critical. Adjustment of
the existing psychotropic regime may be necessary. Some require downward
increments of antipsychotic medications, particularly if the cancer has CNS
involvement. A minority require higher doses. Irrespective of the particular
antipsychotic medication the patient may be maintained on, it is still advisable
to use additional haloperidol as first-line medication in delirium (see Chapter 9).
If the delirium reverses then the haloperidol is able to be withdrawn, and the
original antipsychotic regime remains in place.
Institutionalised patients often consider the psychiatric hospital their ‘home’,
and wish to be managed in this familiar environment by nursing staff, whom
they know and trust, until death. The oncology ward or the hospice are new
situations and perhaps too difficult to contemplate. ‘Their own’ nursing staff are
generally delighted to respond, with palliative care support, to the new challenge
of terminal care.
ALCOHOL DEPENDENCY
Oblivion is a kind of Annihilation.
Thomas Browne (1605–82)17
Heavy and sustained alcohol use is a risk factor for many malignancies. Many
decide not to alter their alcohol consumption after the emergence of a terminal
illness. Some reform. All experience, but rarely will discuss, the guilt and the
regret of substance- and self-induced disease. Establishing psychotherapeutic
relationships at this stage is most difficult. Invariably, many past attempts at
therapy and sobriety have failed. Most interpret these failures of therapy as ‘not
their fault’. They project blame onto many of the well-meaning and competent
clinicians involved, rather than acknowledge personal responsibility for harmful
and antisocial behaviours. Personality, mental ill health and circumstances may
have led to the excessive reliance on alcohol. Decades of such behaviour and
consequent mild brain damage create a rigid and unpsychological style of coping,
and making psychotherapeutic gains is resisted. In crises, the coping strategy so
commonly used by alcoholics is to use alcohol and induce a state of oblivion. It is
not infrequent that such patients in their terminal phase request deep sedation.
Because of past alcohol use (and often prior exposure to benzodiazepines) higher
sedative dosage than usual may be required. Delirium tremens (DT) should be
considered if a sudden alteration of behaviour and consciousness occurs 2–3
days after an admission (see Chapter 9). Alcoholic hallucinosis is usually asso-
ciated with the withdrawal of alcohol use, and less commonly with resumption
of use after a dry period. Wernicke’s encephalopathy (weakness, peripheral
neuropathy, ophthalmoplegia), a thiamine deficiency state, is associated with
alcoholism, but can be secondary to malabsorption syndromes and inadequate
vitamin supplementation in feeding regimes of cancer patients.
Alcoholics have families, many of whom have been damaged by the patient’s
lifestyle and a few of whom are codependent. Invariably, a distressed and dis-
turbed family raises issues for palliative care staff. While these families should
not be treated differently from others, they may well deserve the expertise of
services other than palliative care. A crisis is a therapeutic opportunity, and
irrespective of the past it may be the occasion to forge a different future for the
surviving family.
SUBSTANCE ABUSE DISORDERS

Substance use is a major risk factor for cancer and AIDS. Smoking and illicit
drug use is unhealthy. These facts are public knowledge. How the individual
comes to terms with the awareness that these habits are causing their demise
depends on the circumstantial and psychological reasons initiating such risky
behaviours. Veterans of World War II may hold their respective military services
responsible for encouraging and supplying cigarettes. Developmentally trauma-
tised individuals may have been forced into, or found temporary respite in, drug
use. There are as many explanations as there are drug-using patients. Drug use
in most communities is increasing. The modern control emphasis is on ‘harm
minimisation’ rather than abolition. Influencing mankind’s innate interest in
mind-altering drugs and stopping illicit supply have proven rather ineffective.
Over future decades, more terminally ill persons with substance abuse histories
will be attended to in palliative care.
Street drug use by opioid-dependent and addicted cancer patients poses
major difficulties in palliative care settings. They may have been expelled from
drug maintenance services for the crisis of their physical health persuaded them
to abandon the rules of the programme. Having decided that death is now inevi-
table, risk-taking behaviours may escalate. Careless and fatal miscalculations
of street supplies can result, as may admission to general hospitals with acute
cellulitis or endocarditis. Doctors’ opiophobia may result in pseudo-addiction,
the patient seeking additional medication secondary to inadequately managed
pain.18 The terminally ill opioid-dependent cancer patient will require a main-
tenance dose of opioid plus an analgesic dose (see Box 14.1). Methadone is the
usual maintenance opioid in drug programmes because of its long half-life and
limited diversion prospects. Buprenorphine and naltrexone are more difficult to
supplement with analgesics.19 Generous dosing regimes are required to achieve
pain relief. This may be related to a ‘tolerance memory’ or more probably to
the fact that the underlying personality is poorly practised in, or incapable of,
delaying gratification. The required dosage is the sum of the estimated mainte-
nance dose and a usual starting dose of an opioid. There is an incorrect patient
belief or perception that methadone is not equi-analgesic to morphine (see
Chapter 6). Methadone’s NMDA antagonism property is indeed a theoretical
advantage. What remains pharmacologically mysterious is the required use of
twice-daily dosing of methadone as an analgesic, but only once daily for drug
dependency. Using a different opioid for analgesia in maintenance patients is
favoured by some. Morphine and oxycodone may not be preferred because of
their street appeal. The misuse potential of transdermal fentanyl is less, though
straining fluid through the ‘fentanyl tea-bag’ is reported. Buprenorphine, which
has mixed opioid agonism and antagonism (and can also be combined with low-
dose naloxone), is another option.
BOX 14.1 Prerequisites for the use of opioids in terminally ill drug-abusing
patients
1 Comprehensive clinical assessment: physical/psychosocial/psychiatric

(including drug history).
2 Consent (informed, written).
3 Treatment agreement: prescribing ‘rules’, urine testing.
4 Therapeutic analgesic trial.
5 Collegial second opinion.
6 Nominated single prescriber.
7 Review, review, review (analgesia, aberrant behaviour, adverse reactions).
It is difficult to ascertain the quantities of medicinal opioids diverted for illicit

use. In India there were no reports of diversion from a home-based palliative care
service,20 whereas in the USA misuse of oxycodone is ‘widespread’.21 The steep rise
in deaths from unintentional opioid drug overdoses in the USA since the early
1990s parallels the increase by a factor of 10 in the medicinal use of opioids over
this period.22 While this doesn’t necessarily imply that these drugs were obtained
illicitly it attests to the easy availability of opioids in the community and perhaps
to reckless self-administration. While being cognisant of this risk of diversion,
the prescriber’s primary obligation is to the patient and the medicinally estimated
requirement. Measures to try to reduce these risks are to provide supplies for short
periods, random urine checks, not being accepting of the multiplicity of explana-
tions and ‘stories’ about early exhaustion of supply, and eliciting family involvement
in monitoring use (if in the home and the family are willing and capable). These
patients are extraordinarily time-consuming to manage. The most careful practi-
tioner can be seduced by a clever and experienced drug seeker, who also has cancer.
Possibly the most likely source of opioid drug diversion in palliative care is that of
the ‘wayward grandchild’ who visits the dying grandparent with a purpose.
ANXIETY DISORDERS
Anxiety is an inevitable consequence of severe medical illness. In those predis-
posed to anxiety, the jags of enhanced anxieties during the course of illness are
liable to exacerbate the underlying anxiety disorder. The anticipation of feared
events can be worse than the actual enduring of the event. Maintenance of
existing anxiolytic regimes, both psychological and pharmacological, is critical.
Boosting with additional therapies may be warranted. Preparatory information
and reassurances concerning a necessary forthcoming procedure, the addition of
short-term benzodiazepine, and the scheduling of extra psychotherapy sessions
can be useful. Prophylactic anxiolysis with an SSRI (the most effective pharma-
cotherapeutic agent for persisting anxiety) warrants consideration. Those who
appear psychologically fickle and vulnerable can surprise. Courage and fortitude
are not related to anxiety.
POST-TRAUMATIC DISORDERS
Cancer, life-threatening medical illness, medical procedures and treatments
may induce acute stress reactions (ASR) and PTSD. A diagnosis of cancer is a
‘traumatic stressor’, particularly for young women with breast cancer. The risks
of illness inducing an ASR or PTSD are uncertain, probably less than 5%.23
Many have sub-clinical symptoms of these disorders, symptoms characterised
by intrusions centred on future-orientated events (e.g. clinical deterioration)
and anxious apprehension, rather than the traumatic reminiscences of combat
PTSD patients.24
Those who have survived terrifying life-threatening experiences, events

precipitating a chronic PTSD, may when confronted with a terminal illness expe-
rience a rekindling of the original trauma. The return of traumatic night terrors
and intrusive thoughts, enhanced startle and flashbacks, all perhaps previously
contained, again trouble the sick patient. This can be an early indicator of nerv-
ous system involvement of cancer. The cognitive impairment may result in the
loss of the previously effective suppression and coping mechanisms. More prob-
ably the illness serves to psychologically reactivate the veteran’s past. This current
confrontation with death reminds them of the previous occasions. Cachexia and
weakness serve as physical cues to these memories.
Often isolated and avoidant persons, distrustful of authority, fearful of loss
of control, and poorly medically compliant, chronic PTSD sufferers struggle to
establish a therapeutic alliance and may present very late.25 Patients suffering
PTSD have high substance use comorbidity and propensity to self-medicate.26,27
Depression may be a complicating factor and deserving of assertive interven-
tions. Antidepressant medications, benzodizapines, adrenergic receptor-blockers
(e.g. clonidine) may calm anxiety, panic, hyperarousal and avoidant symptoms
in some.25 Psychoeducation about the disorder coupled with medication and
supportive psychotherapy, may ease the resurgence of symptoms. Opioids may
be protective against the development of PTSD.28 PTSD has been conceptualised
as an endogenous opioid deficiency state,29 similar to an opioid withdrawal syn-
drome. Opioid dysregulation occurs in PTSD.30 The precise receptor involved is
uncertain. Medicinal opioids and benzodiazepines serendipitously may relieve
post-traumatic symptoms.
ANOREXIA NERVOSA
Anorexia nervosa has the highest mortality of any psychiatric disorder. Of the
20% who develop a chronic course of the disorder, some are refractory to treat-
ment.31 After many years of intensive and often necessarily coercive treatment
regimes a stage of palliative care can be reached.32 Assessing the competency of
a starved and wasted young person, excluding affective and psychotic comor-
bidity, and determining a position of medical futility, are difficult clinical issues.
Withdrawing aggressive treatments and maintaining supportive and comfort
care is the sad but humane position occasionally agreed upon by patient, family
and doctors as a management of last resort.
INTELLECTUAL DISABILITIES
Emotions are often converted to behaviour in these patients. Grief may be
expressed as bad, but really sad, behaviour. A change from usual behaviour
should alert the carers to the possibility of a psychological cause. Insecure and
overprotective developmental attachments are not uncommon.33 Personality
fragility compounds the intellectual limitations. Many intellectually disabled

individuals are able to learn new information and from experience. But the
learning is slow. When confronted with the crisis of serious illness the grasp
of the information is laborious, if possible at all. Learning about ageing, illness
and death is delayed in those who are intellectually less able.33 If living with
family, the mother–‘child’ bonding is likely to be intense, perhaps ambivalent.
Communication may only be possible using the family as interpreters, who may
not wish to relay the medical realities. While respecting the family’s knowledge
and intuitions, it is important to try to ascertain the patient’s cognitive appraisal
of their predicament.
REFERENCES
1 Cervantes. Don Quixote. Cohen JM, trans. Harmondsworth: Penguin Books; 1952.
pp. 936–8.
2 Felker B, Yazel J, Short D. Mortality and medical comorbidity among psychiatric
patients: a review. Psychiatric Ser. 1996; 47: 1356–62.
3 Rouillon F, Sorbara F. Schizophrenia and diabetes: epidemiological data. Eur Psychiatry.
2005; 20(Suppl. 4): S345–8.
4 Foti ME. ‘Do it your way’: a demonstration project on end-of-life care for persons with
serious mental illness. J Palliat Med. 2003; 6: 661–9.
5 Howard LM, Barley EA, Davies E, et al. Cancer diagnosis in people with severe mental
illnes: practical and ethical issues. Lancet Oncol. 2010; 11: 797–804.
6 Catts VS, Catts SV, O’Toole BI, et al. Cancer incidence in patients with schizophrenia
and their first degree relatives – a meta-analysis. Acta Psychiatr Scand. 2008; 117: 323–6.
7 Barak Y, Achiron A, Mandel M, et al. Reduced cancer incidence among patients with
schizophrenia. Cancer. 2005; 104: 2817–21.
8 Tran E, Rouillon F, Loze J-Y, et al. Cancer mortality in patients with schizophrenia: an
11-year prospective cohort study. Cancer. 2009; 115: 3555–62.
9 Woods A, Willson K, Kington C, et al. Palliative care for people with severe persistent
mental illness: a review of the literature. Can J Psychiatry. 2008; 53: 725–36.
10 Lo B, McLeod GA, Saika G. Patient attitudes to discussing life-sustaining treatment.
Arch Int Med. 1986; 146: 1613–15.
11 Foti ME, Bartels SJ, Merriman MP, et al. Medical advance care planning for persons
with serious mental illness. Psychiatric Ser. 2005; 56: 576–84.
12 Macleod AD. Respiratory depression and melancholia. Int J Psychiatry Med. 1990; 20:
383–91.
13 Freud S. Beyond the Pleasure Principle: the standard edition of the complete works, Vol 17.
London: Hogarth Press; 1954. p. 33.
14 Borchardt CM, Popkin MK. Delirium and the resolution of depression. J Clin Psychiatry.
1987; 48: 373–5.
15 Talbot JA, Linn L. Reactions of schizophrenics to life-threatening disease. Psychol Q.
1987; 50: 218–27.
16 Goldenberg D, Holland J, Schachter S. Palliative care in the chronically mentally ill.
In: Cochinov HM, Breitbart W, editors. Handbook of Psychiatry in Palliative Medicine.

Oxford: Oxford University Press; 2000. pp. 91–6.
17 Browne T. Christian Morals. pt. 1, xxi. Quoted in: The Oxford Dictionary of Quotations.
3rd ed. London: Book Club Associates; 1981. p. 95.
18 Weissman DE, Haddox JD. Opioid pseudoaddiction – an iatrogenic syndrome. Pain.
1989; 36: 363–6.
19 Alford DP, Compton P, Samut JH. Acute pain management for patients receiving main-
tenance methadone or buprenorphine therapy. Ann Intern Med. 2006; 144: 127–34.
20 Rajagopal MR, Jorenson DE, Gilson AM. Medical use, abuse, and diversion of opioids
in India. Lancet. 2001; 358: 1182–3.
21 Cicero TJ, Inciardi JA, Munoz A. Trends in abuse of oxycontin and other opioid anal-
gesics in the United States: 2002–2004. J Pain. 2005; 10: 662–72.
22 Okie S. A flood of opioids, a rising tide of deaths. N Eng Med J. 2010; 363: 1981–3.
23 Andrykowski MA, Cordova MJ. Factors associated with PTSD symptoms following
treatment for breast cancer: test of the Anderson model. J Trauma Stress. 1998; 11:
189–203.
24 Mundy E, Baum A. Medical disorders as a cause of psychological trauma and post-
traumatic stress disorder. Curr Opin Psychiatry. 2004; 17: 123–7.
25 Fieldman DB, Periyakoil VS. Posttraumatic stress disorder at the end of life. J Palliat
Med. 2006; 9: 213–18.
26 Chilcoat HD, Breslau N. Post traumatic stress disorder and drug disorders: testing
causal pathways. Arch Gen Psychiatry. 1998; 55: 913–17.
27 Bremner JD, Southwick SM, Darnell A, et al. Chronic PTSD in Vietnam combat vet-
erans: course of illness and substance abuse. Am J Psychiatry. 1996; 153: 369–75.
27 Bryant RA, Creamer M, O’Donnell M, et al. A study of the protective function of acute
morphine administration on subsequent posttraumatic stress disorder. Biol Psychiatry.
2009; 65: 438–40.
28 Holbrook TL, Galarneau MR, Dye JL, et al. Morphine use after combat injury in Iraq
and post-traumatic stress disorder. N Eng Med J. 2010; 362: 110–17.
29 Kosten TR, Krystal J. Biological mechanisms in PTSD: relevance for substance abuse.
Recent Dev Alcohol. 1998; 6: 49–68.
30 Friedman MJ. What might the psychobiology of PTSD teach us about future approaches
to pharmacotherapy? J Clin Psychiatry. 2000; 61(Suppl. 7): 44–51.
31 Steinhausen H. The outcome of anorexia nervosa in the 20th century. Am J Psychiatry.
2002; 159: 1284–93.
32 Lopez A, Yager J, Feinstein RE. Medical futility and psychiatry: palliative care and
hospice care as a last resort in the treatment of refractory anorexia nervosa. Int J Eat
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33 Blackman N. Supporting bereaved people with intellectual disabilities. Eur J Palliat
Care. 2005; 12: 247–8.
CHAPTER 15
Euthanasia and psychiatry
Nor is death the worst we can look for; lingering life, and death denied, may
be still deadlier.
Sophocles (496–406 BC)1
Euthanasia is killing on request. Physician-assisted suicide (PAS) is defined as

‘a doctor intentionally helping a person to commit suicide by providing drugs
for self-administration, at the person’s voluntary and competent request’.2
Withholding futile treatment, withdrawing futile treatment, and palliative seda-
tion are not considered euthanasia.2
Historically, medicine has been opposed to legalised euthanasia. The general
public has a differing view and is increasingly vocal about the deficient care of the
dying. Palliative medicine, psychiatry and general practice are starting to more
studiously consider the complexities of these issues. Several specialist medical
colleges in the UK have shifted to a neutral, rather than an opposed, stance.
Legalised euthanasia and/or physician-assisted suicide (PAS) are practised in the
Netherlands, Belgium, Estonia, Luxembourg, Albania, Switzerland and the States
of Oregon, Montana and Washington, USA. Valuable knowledge and opinion are
being gained from these experiences. Euthanasia is a crisis that modern medicine
must attend to. Psychiatry, unwillingly, has the key role in those jurisdictions in
which euthanasia law has been passed, for it is the gatekeeper for euthanasia.
THE EUTHANASIA DEBATE

Over the last 50 years there has been a dramatic shift in both the location of death
and the responsibility for the dying. Previously, families cared for their sick in the
home and the care was governed by the personal, societal and religious beliefs
of these individuals. Now most deaths in developed countries occur in public
institutions. The care is governed by the society mores. Issues about euthanasia
have become common and public ones. Over the same period, medicine became
209
scientifically capable of artificially sustaining life. For the first time the very sick
have options of living or dying. Euthanasia debates do not occur in societies
without health services sufficiently affluent to be able to keep persons artificially
living.3
There are several core viewpoints presented within the debate:
1 The right of autonomy: individuals, particularly in Western countries, demand
the right to chose if and when they die. Since the 1970s a more radical inter-
pretation of autonomy has allowed patients not only the right to refuse an
unwanted medical intervention, but the ability to demand specific treatments
that doctors had not offered.4
2 Religious sanctions: most traditional religions believe God decides time of
death and not the individual.
3 Suffering: if severe and unrelieved then it is humane (with permission) to kill
the sufferer.
4 Financial: the ageing population will result in too few young persons able to
care for their elderly, and investing funds to support and extend the nursing
profession is not considered a priority. From a financial perspective, curtailing
the duration of the final illness would be cost beneficial to a society.
5 The ‘slippery slope’: mankind is not responsible, as proven by history. The
accepted criteria for euthanasia will eventually be exploited for political or
other advantages.
The only one of these viewpoints of relevance to medicine (the profession rather
than the individual) is that of suffering. Palliative care, the discipline, has, since
its modern establishment, opposed legalised euthanasia. The viewpoint is that
suffering can be relieved for the majority by palliative care expertise, and pallia-
tive sedation allows control of symptoms if all else proves ineffective. Whenever
the Roman emperor Augustus heard of anyone having passed away quickly and
painlessly, he used to pray, ‘May Heaven grant the same euthanasia to me and
mine’.5 The quest for a good death, an easy death, painless and without suffer-
ing, remains elusive. The process of dying ‘badly’ (dysthanasia) is an inherent
fear, ‘dying with dignity’ a hope. Increasingly, fear of dying rather than fear of
death is a dominant concern of developed societies. An ageing population and
medical technology able to sustain life have influenced this changing anxiety. An
‘appropriate death’ has four outstanding characteristics: awareness, acceptance,
propriety and timeliness.6 Palliative medicine is committed to providing good
symptom control and ultimately a good death (see Box 15.1).7 The criteria for a
‘good death’ may be more easily fulfilled by euthanasia than by allowing nature
autonomy.
EUTHANASIA AND PSYCHIATRY 211
BOX 15.1 Principles of a good death7
● To know when death is coming, and to understand what to expect.

● To be able to retain control over what happens.
● To be afforded dignity and privacy.
● To have control over pain relief and other symptom control.
● To have access to information and expertise of whatever kind necessary.
● To have access to any spiritual and emotional support required.
● To have access to hospice care in any location, not only hospital.
● To have control over who is present and who shares the end.
● To be able to issue advance directives which ensure wishes are respected.
● To have time to say goodbye, and control over other aspects of timing.
● To be able to leave when it is time to go, and not to have life prolonged
pointlessly.
LEGALISED PHYSICIAN-ASSISTED SUICIDE

In 1996, for the first time in history, a democratically elected government made
both euthanasia and PAS legal. The following year the Australian government
overturned this Northern Territory state law. In nine months, seven patients had
made formal use of this law and four died under it.
In the Netherlands, euthanasia and PAS have been sanctioned and practised
openly since 1991. In 2002 PAS was made legal. The criteria for euthanasia in
Holland are listed (Box 15.2).8 The Dutch have made strenuous effort to record,
document, and research their practices of assisted dying. In 2001 about 2.6% of
all Dutch deaths were by euthanasia.9 The numbers are steady, perhaps falling, for
in 2005 this percentage was 1.8% and in 2007 it was 1.7%.10,11 However, over this
same period continuous deep sedation was used more commonly (5.6% of deaths
in 2001, 7.1% in 2005).10 About 3000 persons per annum are ‘therapeutically
killed’. The percentage of cases officially reported has steadily increased since
1990 from 18% to 54% in 2001 and 80% in 2005.12 In most cases of euthanasia
in the Netherlands the patient’s life is shortened by less than a month.13
In 1997 the state of Oregon, USA, legalised PAS, but not euthanasia. Terminally
ill persons suffering ‘incurable’ and ‘irreversible’ disease considered to be in the
last 6 months of life, who are competent and not depressed may request PAS.
This is determined within 15 days of their request. The family need not be noti-
fied. The patient is prescribed a supply of lethal medication (a barbiturate) to
be consumed orally. About 50–60 persons/year request PAS. Between 1998 and
2004 only 326 prescriptions were given, and 208 ended their life this way (36%
dying naturally).14 PAS accounted for 0.1% of deaths in Oregon in 2007. In 2008,
88 lethal prescriptions were written and 60 assisted suicides recorded.8 The state
BOX 15.2 Dutch euthanasia criteria, 20028
● The patient must repeatedly and explicitly express the desire to die.
● The patient’s decision must be well informed, free and enduring.
● The patient must be suffering from severe physical or mental pain with no
prospect of relief.
● All other options for care must have been exhausted, or refused by the
patient.
● The patient must be 12 years or over.
● Euthanasia must be carried out by a qualified physician.
● The physician must consult at least one other physician.
● The physician must inform the local coroner that euthanasia has occurred.
of Washington has recently passed legislation very similar to that of Oregon, and
in Montana doctors will not be prosecuted for helping terminally ill patients die.
Belgium legalised euthanasia in 2002, but not PAS or any other forms of
life-shortening action.8 To date the Belgian experience has not been not widely
reported. Belgium is the only country where mental suffering from either
somatic or mental disorder is explicitly acknowledged in law as a valid basis for
euthanasia.9 The mentally ill person must be competent, continuously suffering
unbearably, repeatedly express and record a wish to die, and be experiencing a
severe and incurable disorder. Euthanasia represented 1.9% of all Flemish deaths
in 2007.15 The reporting rate of cases considered by the physician to be euthanasia
in Flanders in 2007 was 93%.15 However, of the total of independently estimated
cases of euthanasia in the district only 53% were reported, suggesting somewhat
as yet selective reporting.15
Since 1942 the penal code in Switzerland has not criminalised assisted suicide,
provided the person who assists is ‘motivated by “unselfish” reasons’.8 Inspired by
stories of suicide to defend family honour or because of romantic rejection, the
Swiss law on creation did not envisage assisted suicide from a medical perspec-
tive.16 Active euthanasia is illegal. A medical practitioner must assess the patient’s
decisional capacity and prescribe a lethal dose of barbiturate. The patient must
administer their own fatal dose. The person seeking assistance does not have
to be terminally ill. They do need to be ‘unbearably suffering’ or ‘unreasonably
disabled’, and consistently expressing a wish to die. Non-medical volunteers
facilitate assisted suicide. Non-physician volunteers determined that in 5% of
114 cases the relatives had explicitly disagreed with the suicide.17 Since 1998
nearly 1000 deaths have occurred under this arrangement including more than
100 Britons (or 16/year) and several Germans, for the patient does not need to
be a Swiss national.18 Of 1800 Swiss requests for PAS each year, two-thirds are
rejected after screening and half of the remaining die by natural causes, leaving
about 300 assisted suicides each year (or 0.45% of deaths in Switzerland).19
PAS REQUESTS AND PERMISSIONS

It is uncertain how frequent the occurrence of unsanctioned doctor-assisted
dying is in countries in which euthanasia is illegal. It is estimated that approxi-
mately 900 patients each year in the UK are helped to die by their doctor at
their explicit request.20 Estimates in the USA are that 3.3% physicians had writ-
ten a prescription with the primary aim of ending their patient’s life, and 4.7%
had given a patient a lethal injection.21 Perhaps between one in 100 and one in
250 deaths in the USA may be attributable to assisted suicide or euthanasia.
But such studies are rather flawed for, even anonymously, few clinicians would
be prepared to reveal an illegal act. Additionally, many doctors (and relatives)
presume an analgesic dose several hours before death caused death, rather than
eased pain until the imminent natural death occurred. The classical example
of this phenomenon is Dr Schur’s ‘voluntary euthanasia’ of the 83-year-old
Sigmund Freud, dying of cancer.22
Public opinion polls suggest over 80% support euthanasia legalisation in the
UK.23 There is a trend that as an individual moves from the street, to oncology
outpatients, then to hospice care, their attitude toward liberalising euthanasia
mellows. In the Netherlands 7% of all people whose imminent death is expected
request euthanasia preceding their death.24 Having initiated the process 13%
then withdraw prior to natural or unnatural death. 25 About 17% of Oregonians
are potentially interested in aid in dying, though only 1–2% actually request it,
26
and 36% of those provided a lethal prescription die naturally.14 In Canadian
palliative care patients 63% believed euthanasia should be legalised, yet only 6%
would wish to initiate the request.27 In a Swiss study of 39 palliative care patients
within a month, of the 23 survivors, 61% had withdrawn their request.28 The
proximity to the deathbed contaminates opinion.
This may also apply to medical practitioners. It is difficult to summarise the
views of doctors on euthanasia issues. The majority of medical practitioners in the
UK and Europe seem opposed to assisted dying, though perhaps a slim majority
express support for PAS, provided rigid safeguards are in place.29 Physicians are less
often in favour of actively shortening life than are the general public and nurses.30
Specialities such as palliative care, geriatrics and oncology appear more strongly
opposed than intensive care physicians and medical students.30,31 Older doctors
are more likely to oppose euthanasia and the religion of the doctor is an obvious
influence.32 The ethnicity of the doctor does not appear to be a major influence.32
However, there is huge geographical variation across the European continent,
and not an obvious north–south difference of view.30 The UK House of Lords
summarised doctors’ views as, ‘The closer their experience of end-of-life patients,
the less sure professionals are about the prospect of a change of the law in favour
of euthanasia’.33 Requests for euthanasia are not uncommon in medical practice,
though the literature is highly inaccurate. Patients cared for at home are more
inclined to request assistance dying than those in hospital whom are more likely
to request non-treatment.34 In a study published in 2000, up to 30% of Northern
Ireland GPs over the preceding 5 years had been asked to perform euthanasia.35 In
North America 20% of physicians have received at least one request, 11% in Italy,
and 45% in Australia.36 In palliative medicine such requests are, however, rare
occurrences. Proximity to death influences the views of patient and doctor.
It might be reasonable to presume that those requesting a hastened death
would be frail and suffering severe pain or other unpleasant symptoms. In the
Netherlands cancer is the commonest diagnosis (74%, mainly gastrointestinal
and lung), 7% have cardiovascular disease, and 5% severe pulmonary disease.
However, relatively, a greater number of patients (20%) with MND die due to
euthanasia or PAS compared with patients with cancer (5%) or heart failure
(0.5%).37 The diseases of those who made requests for PAS in 2000–01 were
physical disease (92.6%) and psychiatric disease (2.9%), though 4.5% described
as being ‘weary of life’ made requests.38 There is a negative correlation between
age and euthanasia.24 The mean age of the requester was 67–68 years. Most were
being nursed at home.24,39 The most important concerns were non-physical.39
Usually the concerns were multifactorial and included fears of dependence, loss
of autonomy, loss of dignity, being a burden on others, and social isolation.39
Loss of control appeared a core influencing factor. Of the three major factors
the personal/social ones (‘tired of life’) were more relevant in encouraging the
request than were the physical and psychiatric ones.12 The characteristics of the
‘weary’ patients were old age (average 81 years), ‘reasonable’ health, aloneness,
and social isolation, but also ‘through or tired of living and physically deterio-
rating’.38 These discontented citizens request ‘suicide-by-doctor’. In the physical
group, 42% of the requests were granted, none in the psychiatric group and
1% in the ‘ weary’ group.38 Suffering in the absence of severe disease is not an
accepted indication for PAS,38 even though the commonly used term sanction-
ing aiding death, ‘unbearable suffering’, has no generally accepted definition in
the Netherlands.40 In only about one third of those who request euthanasia is it
performed.24 Thirty-nine per cent had died before the request could be granted
and 38% did not meet the necessary criteria to allow euthanasia.24
The Oregonian data suggests that patients do not request PAS because of
unrelieved physical symptoms, or inadequacy of palliative care services (most are
simultaneously enrolled in hospice programmes), and neither are they depressed
or socially vulnerable.41 They request assisted suicide for psychological and
existential reasons: they value control, dread dependence on others, are ready to
die, and assess current quality of life as poor.41 The most important reasons for
their requests concerned loss of control, wishing to die at home, loss of dignity
and independence, concerns about future pain, poor quality of life and self-care
ability.42 Significantly, the requests do not relate to distressing physical symptoms
nor financial concerns, poor social support or depression. The concerns were
about future worries of declining welfare. The majority who request PAS are in
their seventh decade, well educated, middle class, white, married with cancer
diagnoses (most commonly lung), and complaining of loss of enjoyment and
quality of life. Between 1998 and 2005 only 8% had MND and 2% AIDS. The
poor, the ill-educated, the uninsured and those without access to palliative care
are not those who request PAS.
Contrary to what may have been predicted (and is assumed by the general
public), those that have the legal opportunity request assisted dying because of
psychosocial, and not physical, symptoms.
PSYCHIATRY IN PHYSICIAN-ASSISTED SUICIDE JURISDICTIONS

The objectives for psychiatric involvement in euthanasia requests, as detailed by
legislators in the respective countries, are to determine mental competency and
to evaluate mental ill health. These are reasonable clinical tasks to be asked of
psychiatry. However, in the terminally ill these are not simple and straightfor-
ward clinical determinations.
Under the law of the Northern Territory, Australia, the patient had to be
certified to be of sound mind with the ability to make decisions freely, volun-
tarily, and after due consideration.9 A psychiatrist was required to examine the
patient and confirm that the patient was not suffering from a ‘treatable’ clinical
depression. Four of the seven patients considered (two died before the law came
into effect, one after its repeal) had some symptoms of depression. One, despite
current depressive symptoms and a probable subtherapeutic dose of antidepres-
sant, was considered to be ‘depressed consistent with her medical condition’. The
other three to die were considered competent and not depressed. The psychiatric
assessment was mandatory, raising concerns regarding cooperation, honesty and
trust issues.43 Indeed, one patient assessed withheld relevant history.43 No ongo-
ing assessment or psychiatric treatment was offered or proposed. The psychiatrist
merely functioned as the (open) gatekeeper to PAS in this situation. The opinions
would appear to be at best cursory.
In the Netherlands physicians ask for a psychiatric evaluation for patients
requesting PAS in only 3% of cases.44 However, if a psychiatrist or psychologist
has already been involved in a patient’s terminal care it is twice as likely that a
request for euthanasia is made (likewise for palliative medicine involvement).24
This may be merely an indication of case complexity. Since the law change in
2002, the person does not need to be competent when ‘euthanased’. An advance
request can be made, which remains valid despite altering health status. In 1995,
of 4500 cases of active termination of life, 20% were without the patient’s request.9
Minors aged over the age of 12 years can request PAS, provided that the par-
ents have been consulted (though they can not veto their adolescent’s request).
The Dutch medical fraternity believe that a person can have a death wish and
not be clinically depressed.37 To date most requests for those suffering mood
disorders have been declined as there were still psychiatric treatment options
left.2 Ultimately, the decision to enact PAS rests on how the doctor considers the
patient’s suffering. It could be argued that it is not patients exerting autonomy,
but doctors exercising power.9 Objective criteria assessing suffering are neither
available nor indeed possible. How the suffering is determined to be ‘unbearable’
rests upon the impression of the assessing doctor for there is no formal defini-
tion of this term.40
In Oregon if the primary physician believes a psychiatric disorder is present,
the patient must be referred to a psychiatrist or psychologist. The poor ability
to detect psychiatric disorder by primary care physicians is well recognised.44
Only 6% of psychiatrists were confident that on a single consultation they could
determine if mental disorder was influencing the request. There is no established
threshold for determining whether a patient is competent to choose suicide.44
Depression (in Oregon) may or may not invalidate a voluntary request, and
treatment of depression only improves the desire for life-sustaining therapy in
a minority.43–45
The key task for psychiatry in Belgium is the assessment of competency in
those whom the treating doctor thinks will not die in the foreseeable future.9
These are generally those patients with mental illness. Competence is not defined
in the law. Depressive disorder and demoralisation may influence the ability to
rationally assimilate information and make decisions; psychiatric illnesses are
not as well understood as diseases such as cancer, and as yet there is considerable
uncertainty (and criticism) about the practice of this aspect of the Belgian law.9
The current provision of psychiatric assessment, as legislated in these jurisdic-
tions, would appear to be inadequate to perform the task expected. The current
knowledge of the psychiatry of the terminally ill, and experience to date in these
countries, raises the probability that the legal expectation of psychiatry is not
achievable.
THE PROBLEMS FOR PSYCHIATRY

Medical futility
It is the duty of a doctor to prolong life. It is not his duty to prolong the act
of dying.
Lord Horder of Ashford (1871–1955)46

The notion of ‘medical futility’ first appeared in the 1980s in response to the
increasing requests to doctors for treatment that patients felt entitled to.4 It
concerns the ethical and legal authority a doctor has in decision-making. If a
treatment is medically futile, a doctor has the power to withhold it (or withdraw
it), even over the objections of a competent patient (or proxy). Resuscitation
need not be attempted if considered that the medical prospect of success is nil or
negligible. Medically assessing futility should ideally be scientifically determined
according to a quantitative parameter and not be the subjective and paternalis-
tic opinion of the attending doctor. This has yet to be achieved and is probably
unachievable. In palliative care we even struggle to provide accurate prognoses.
Adding a qualitative measure introduces the same issues that beset the attempts
to measure ‘quality of life’. Many aspects of assessing the value of remaining life
involve psychosocial influences. How can we assess the suffering of another or
whether the acquisition of rare medical complication in the process of perform-
ing an intervention would be acceptable to the patient? Is an extra day more or
less of life worth the risk–burden ratio? Should valuable medical resources be
‘wasted’ on those unlikely to benefit? Is a less than 1% chance of improvement
futile or warranted? No public or professional consensus has, or can be, reached
on these imponderable issues. By copious discussion (and sometimes frank
argument), practice guidelines, multidisciplinary debates, legal advice, user-pays
medical service options, sensational publicity, and time-consuming negotiations,
modern medicine muddles on with a ‘procedural’ approach. If the physiological
outcome that the patient desires can’t be achieved, or is very unlikely to be so,
then it is likely to be considered by both lay and profession critics to be a futile
intervention. The legal situation is clear in all jurisdictions. Competent patients
cannot demand treatment that clinicians believe to be futile.47 It ultimately relies
on the experience, the wisdom, the leadership, and perhaps the arrogance of the
doctor to decree a treatment futile. Fortunately sensible patients and doctors
usually reach a compromise decision before unilateral decisions are forced. It is
as unsatisfactory as paternalistic medicine was, and certainly is not a robust base
to rest decisions about euthanasia upon.
Assessing competency
The prevalence of psychological distress and psychiatric illness in the dying is
high. Affectations of the brain and mind influence judgement and decision-
making. Setting aside judgement impairments due to delusions and thought
disorder, serious emotional turmoil is commonly associated with incapacity.48
Distorted or pathological thoughts may warp judgement. Determining mental
fitness to decide upon life-sustaining or relieving options is at best imprecise
(see Chapter 12). It is contradictory, if not confusing, that for refusal of treatment
with lethal outcome consent must be accepted, whereas for a lethal treatment,
such as PAS, consent is impossible. Assessing capacity in those requesting PAS

is difficult as the cognitive capabilities required to decide on suicide are contest-
able, indeed not known. That ‘therapeutic killing’ is performed without consent
on one in seven in the Netherlands (presumably those incompetent) certainly
provokes concern of a ‘slippery slope’.49 Euthanasia without an explicit request
from the patient amounts to 0.4% of all deaths in the Netherlands.10 Termination
of life on request (euthanasia) is more common in the Netherlands (2.4%), than
Belgium (1.1%), while termination of life without request is more common in
Belgium (3.2% versus 0.7%).15 In a sample of 208 deaths under the euthanasia
law, representing 12% of the deaths during 2007 in Flanders, 32% were admin-
istered life-ending drugs (opioids) without their explicit request.50 The decisions
to terminate the lives of these elderly, hospitalised patients in comatosed or
demented states, who had previously indicated a wish for life not to be need-
lessly prolonged, were made by medical staff in agreement with the family, and
probably only curtailed nature by less than a day.50 Such events are not possible
within the Oregon legislation. It is claimed that there is no evidence from the
Netherlands or Oregon to justify concerns about the negative impact of assisted
dying legislation on potentially vulnerable groups, such as older, uninsured, eth-
nic minorities, minors and disabled people.51 The only group identified to have
a heightened risk were people with AIDS.51 While in the Netherlands it is more
likely to talk about euthanasia than to die a euthanasia death,52 as yet there is not
compelling information from countries allowing assisted death that competency
and consent issues are rigorously adhered to.
Depression and the desire for death

Persistent requests for euthanasia are uncommon in palliative care practice,
though more frequent in primary care. In persons over the age of 65 years,
9.5% have suicidal thoughts, but only 0.14% actually attempt suicide.53 High
desire to die is present in 5–10% of the palliative care population. In severely ill
patients, the will to live fluctuates.54 The will to live is determined more strongly
by psychological variables until the last few days when supplanted by physical
variables such as pain and dyspnoea.55 In terminally ill cancer patients, psycho-
logical distress rather than pain and functional status is the most influential
factor determining the desire for hastened death.56 The strongest factors are
hopelessness, depression and anxiety.56 The wish to die is not stable, especially if
mental health problems are evident.57 Major depression was diagnosed in 59%
of hospice patients who persistently desired a hastened death, but in only 8% of
those who did not.54
In Oregon it is estimated that about 20% of those requesting aid for dying
are depressed,26,57 an expected incidence. Concerned that the professionals and
family members involved with Oregon patients who pursued assisted dying did
not believe depression had influenced their choice, and that in 2007 none of
those who died of PAS had been seen by a psychiatrist or psychologist, investiga-
tors studied the prevalence of depression and anxiety in terminally ill persons
requesting aid in dying.26 Though the investigators struggled to recruit, of 58
Oregonians, 15 met the criteria for depression (HADS and Beck, SCID-I), six
of whom were of the opinion that their depression influenced their preference
for PAS. By the end of the study 42 had died, of whom 18 had been prescribed a
lethal dose, and nine had died by this method. Three (17%) of these 18 decedents
had met the criteria for depression, though one had been successfully treated for
depression prior to her death. It would appear that some cases of depression are
missed or overlooked in the medical assessments. Similar prevalence of depres-
sion has been determined in Swiss persons seeking assistance to die. The largest
right-to-die organisation in Switzerland (Exit) found 27% of those requesting
assisted suicide were ‘depressed’ according to the volunteer assistants,17 and 36%
of hospitalised palliative care patients demanding death were depressed.28 The
clinical problem is that depression in the terminally ill is a complex and difficult
diagnosis to make and depressed (and demoralised) patients are not necessarily
competent.58
Those Oregonians who received substantive intervention such as control of
pain, hospice referral, psychosocial and antidepressant medication, were more
likely to change their mind about PAS.57 They also had less advanced disease.
Only 11% changed their mind after an antidepressant trial.57 Those whose
decision altered were more ambivalent and unstable with regard to the initial
request, not as hopeless, and had a few treatment options still available.35 In
the Netherlands 13% had a change of mind. This was less likely in the terminal
phase and more likely if there were mental health problems.35 Instability of
attitude concerning PAS, generally toward rejection of an earlier supportive
view, occurred in 8–26%, particularly if depression lifted.59 In Oregon, no PAS
patient has contacted emergency services after consuming the lethal medication,
though this would need to be done within 25 minutes.14 In AIDS patients with
a desire for hastened death, 27% had major depressive symptoms and 60% of
these responded well to antidepressant treatment after 2 months and dramati-
cally reduced their wish for an early death.60 Those whose depression did not
respond (37%) had no major alteration in their desire to die early. Depression
does not inevitably account for desire for death but there is a possibility that
treatment of depression may alter the incidence of PAS requests. Existential vari-
ables have a stronger effect on the desire to die than psychological and psychiatric
ones.61 Desire for death may be driven by the intolerable future rather than the
intolerable present.62 Spiritual well-being (a sense of meaning and peace) is an
important modifier of the desire to die, and even if depressed, it is protective.63
The percentages of patients changing their view about PAS, perhaps 10–15%,
while small, would be considered to be an unacceptably high operating mortality

in surgical practice. Of additional concern, and possibly influential in oncologi-
cal practice, is the impression that by offering further treatment options, a view
about euthanasia may alter.35 However these patients had lesser disease burden
and this may be of greater relevance.
Fears of dying
When hope goes, uncertainty goes too, and men don’t fear uncertainty.
Admiral Richard Byrd (1938)64
The fear of dying is universal (see Chapter 2). Often this concerns the proc-
ess more than the event. Uncertainty incites anxiety. Dying patients are more
anxious if death seems probable rather than certain.65 Admiral Byrd, trapped
in the Antarctic winter, alone and unable to be rescued, experienced that hav-
ing accepted the inevitability of his death, his anxiousness settled.64 Knowing
a date of death may flood and then diminish anxieties and fears. Socrates was
free of dread before he drank the hemlock, saying ‘that to be afraid of death is
only another form of thinking that one is wise when one is not; it is to think
one knows what one does not know’.66 The inherent fears of dying and death are
amplified by the enhancing public perception that modern medicine will resus-
citate and sustain life even in those with little prospect of good quality of life.
Advance directives are driven, albeit slowly, by such concerns. Ongoing public
relations exercises by medical researchers that they are on the verge of solving
a disease perpetuate these beliefs. Euthanasia is a reaction to the fear of being
‘kept alive when dead’.
The process of dying is becoming increasingly fraught and difficult. This
is a cost of the curing philosophy of modern medicine. Assertive oncological
treatments, aimed only to prolong life for weeks to months, are allowing cancer
patients to live longer. This also allows the accumulation of disease in multiple
organs, including the brain. Ultimately, the terminal phase of life is influenced
by multiple partial organ dysfunctions and failures. It is probable that because
of this the prevalence of terminal delirium is increasing. The acute mortality of
cancer has been arrested. Cancer has been converted into a chronic illness with
a more complicated death. Many are treated assertively up to and including the
dying stage. Medicine has seemingly lost its clinical judgement and wisdom. It
is easier to do what is technically possible to be done than to consider wisely the
quality of life. Johann Stieglitz (1767–1840) stated: ‘I have often thought it would
be important to instruct physicians how to behave in cases of incurable disease:
not so much to tell them what to do; rather what not to do’.67 In the twenty-first
century this thought is even more pertinent. There was always for Hippocrates a
fundamental question: to treat or not to treat? Making prognoses was a primary
medical function. To help, or at least do no harm, was the Hippocratic tradition.
Modern medicine is predominantly taught in large technologically sophisticated
hospitals by medical researchers with interests in curing rather than caring.
Doctors are not trained to be sensible and sensitive clinicians. Expert clinicians
have been devalued in recent decades within medicine. Making a good bedside
diagnosis of dying, and addressing the situation rather than enacting a proce-
dure, is a skill some learn by experience, but many never learn. That modern
medicine’s care of the dying is deficient ignites in the general public the simplistic
response that orchestrating euthanasia would be a solution.
There are hints in the literature that for some ‘euthanasia talks’ (the nego-
tiations around the request and the process) are in themselves therapeutic.
Euthanasia practice in the Netherlands typically involves extensive delibera-
tions with the patient, the majority of which do not end in a euthanasia death.52
Paradoxically, these discussions tend to affirm social bonds, social life and life.
The provision of a ‘lethal bullet’ may result psychologically in an enhancement
of the patient’s control over their desperate predicament and an augmentation
of their esteem and wish to live until nature determines otherwise. In reference
to Oregonians who decide not to ingest the prescribed barbiturate: ‘Perhaps the
knowledge that they could end their life if they so desired makes them feel less
trapped – therefore freer to keep going’.68
The time of death
All dais [days] march toward death, only the last comes to it.
Michel de Montaigne (1533–92)69
Making accurate prognoses about the time of death is medically difficult. Not
only are there rafts of physiological variables, there are also psychological ones.
All those who work in palliative care recognise that individuals can postpone
death a short while to participate in an important event, and alternatively ‘will’
death if ready. The Sabbath effect, the reduced probability of death on the
Sabbath, has been shown in an Israeli population,70 though a large US popula-
tion study of deaths at Christmas, Thanksgiving and birthdays did not suggest
that cancer patients could postpone death.71 The involvement of the nervous
system, which needs to be considered in investigating this issue, would prob-
ably negate any psychological effect on the timing of death. It is unlikely that
the skill and knowledge to accurately determine time of death will easily be
acquired, particularly as the natural history of cancers is so influenced by medical
interventions, and investigating predilections (or otherwise) of death is difficult.

Sanitising death is unnatural and may be disturbing for relatives, though so may
be waiting, particularly if this period is agonising for patient and family. PAS has
been shown to cause fewer traumatic grief symptoms in the bereaved family,72
and allowed family members to be more prepared and accepting of the death.73
Hospice workers are familiar with the rich and rewarding time many families
endure but appreciate during the vigil awaiting the death of a loved one. Good
palliative care, and ‘good’ assisted dying, improves the outcome of grief for the
relatives. It is uncertain how important being able to anticipate the timing of
death might be for this may be a key influence.
Suicide versus physician-assisted suicide

Suicide is the voluntary and intentional taking of one’s own life. Suicide is
relatively infrequent in cancer patients (see Chapter 8). ‘Psychological autopsy’
studies suggest that 80% of persons with cancer who committed suicide were
clinically depressed, about the same as for those suicides without cancer.74
Suicide prevention has become a major public health issue in response to grow-
ing prevalence in groups of the community, particularly youth. Practising PAS
appears inconsistent with these directives, and provides the general public a
contradictory message. Finlay raises the relevant clinical observation that ter-
minally ill patients are reluctant to kill themselves, yet some wish to be killed by
their doctor.75 Suicide and PAS are perceived to be different by the terminally ill.
Suicide is dear to liberalism, it is a practice of freedom. We live in an age
of suicide risk.76 The history of suicide regulation is pertinent to euthanasia.
Traditionally for the Christian church, and many religions, suicide was a mortal
sin that represented a fundamental rejection of God’s divine authority. Self-
murderers were punished by humiliating spiritual denial, bodily defilement and
excommunication. By the nineteenth century, suicide was considered a criminal
mental disorder necessitating care by the medical fraternity (in dank, appalling
institutions). Doctors contained and controlled suicidal ‘lunatics’ with moral
and physical methods of ‘treatment’. Since the 1970s Western society has started
to consider suicide as a category of risk. Preventing these risks is now largely
performed in the community and by the community. Education, support and
psychology are offered. Freedom (to kill oneself) has been achieved as the state
and medicine have been virtually extruded. However, in dire emergencies of
pronounced and dangerous suicidal behaviours doctors are called, as the doc-
tor is requested to be the executioner in PAS legislations when the gravely ill are
unwilling or unable to commit suicide.
Doctors as executioners
Hippocratic medicine professes to do no harm. Killing patients is a role doc-
tors neither wish for nor want. Anaesthetists, potential executioners because of
their skills inducing states of unresponsiveness, are firmly opposed.77 Indirect
killing as in Oregon, or by a state-appointed executioner, are obvious options,
but hardly fulfil the medical obligation of non-abandonment (see Chapter 3).
In most jurisdictions it is the family doctor who provides and administers the
lethal medications at their patient’s home. Hospitals in Switzerland have barred
assisted suicide from their premises, with one exception, which provoked
considerable staff opposition and debate.78 Nurses in Dutch hospitals are not
infrequently actively involved in the discussions and procedure, even adminis-
tering the euthanatic.79 While numbers are few for most doctors it is clearly not a
pleasant task. In the 1990s the number of Dutch doctors who expressed feelings
of discomfort following euthanasia were 75%, following assisted suicide 58%,
following life ending without an explicit consent 34%, and following alleviation
of pain with high dosage opioids 18%.80 ‘Many physicians who had practiced
euthanasia (in the Netherlands) mentioned that they would be most reluctant
to do so again’.81 In Oregon doctors attending persons requesting PAS report
being intimidated by patients to assist, and of being powerless to influence the
decision-making process.82 In the USA 53% of physicians who reported partici-
pating in euthanasia or PAS were comforted from having helped the patient,
24% regretted being involved and 16% reported that the emotional burden of
performing euthanasia or PAS had adversely affected their medical practice.83
Of participating doctors, 18% reported being somewhat uncomfortable with
their role as the writer of the prescription, and 6% with their administration of
the lethal injection.21 Oregon doctors who had participated, particularly those
involved in the early years, acknowledged the emotional difficulties it aroused.84
It is difficult to gauge the influence on the doctor–patient relationship, for seek-
ers of assisted death most likely select their doctor with this purpose in mind.
Requests may facilitate important end-of-life discussions (‘death talk’). However,
the average length of the professional relationship with the prescribing doctor in
Oregon is only 12 weeks. Oregon doctors highlight the gulf between theoretically
supporting the concept and actually participating in it. They consider themselves
insufficiently prepared, fearful of making errors, and being personally damaged
by the experience.84 It is emotionally draining work.
Doctors may buckle under their own psychological issues. The fatigued, hope-
less and despairing doctor confronted by a patient requesting assisted suicide
may more easily acquiesce or subtly encourage the act. Clinicians burdened with
the care of the very sick, frustrated by their therapeutic impotency, struggling to
communicate effectively, and seduced by the apparent rationality of the request
may become, like their patient, supportive and implicit in quickening death.85 It
appears that the personal and professional experience of therapeutically killing is

discouraging doctors from accepting these patients onto their books and encour-
aging their withdrawing from the process. Doctors in the Netherlands attempt
to find other solutions to euthanasia for self-protection.82 Doctors prefer to cure
rather than extinguish life. Historically, the position of the public executioner
in England and France was an inherited and secret ‘honour’. Killing within the
law is an onerous duty. A component of medicine’s reluctancy to alter the law
is self-serving.
EUTHANASIA AND MEDICINE

Relatively rarely do patients present to palliative care requesting euthanasia.
Doctors working in the community are more likely to field a request for eutha-
nasia. If they do, the clinical problems initiating the request (in developed
countries) are psychosocial and existential rather than medical or psychiatric.
Medicine can only opine on the association of suffering and euthanasia. Mostly,
this suffering has little or no disease involvement. It is not known if the existential
factors initiating a request are in any way remediable to intervention. There are
many concerns regarding the oscillations of the will to die, the effect of depres-
sion on euthanasia requests, and what constitutes fitness to commit rational
suicide. Every medical clinician in palliative medicine has attended individuals
whose state of unremitting and intractable suffering appears unbearable, and
whose wish for euthanasia is persistent. Palliative sedation is an effective and fair
option for these patients. It is not euthanasia by another name, and is an effec-
tive and appreciated medical intervention. The misuse of ‘palliative’ sedation,
when in actuality euthanasia is being practised, is a sinister rationalisation and
a blatant breech of the Principle of Double Effect. Psychology and psychiatry’s
challenge is to better understand these influences so they can perform credibly
as gatekeepers, if legally requested to do so. Concerns of a ‘slippery slope’ remain.
Subjective impression of suffering needs to be supplanted by solid, objective,
evidence-based literature and clinical guidelines. Medicine has a responsibility
to relearn to care for individual sick persons, to teach these skills and to temper
curative hopes and aspirations. Dying needs to be better managed.
Oregon has shown that it is a myth that excellent palliative care is incompat-
ible with legal access to PAS.62 The number of patients who have used hospices
in Oregon has increased from 2000 in 1988 to 15 000 in 2005, and since the
advent of law changes in Holland and Belgium similar trends have been noted
as palliative care services have been developed. In Belgium end-of-life deci-
sions that shorten life were not related to a lower use of palliative care, rather
multidisciplinary care of palliative services intensified the requests to abandon
active treatments but not euthanasia.86 Life-shortening end-of-life decisions are
not prevented by multidisciplinary palliative care services.86 There has been a
synergistic co-evolution of palliative care and euthanasia in Belgium.

Liberalising euthanasia law needs to be accompanied by additional psychiat-
ric and psychological involvement in palliative care and the research necessary
to clarify the uncertainties attached to the mental and cognitive aptitudes of
the terminally ill. While the legal profession may appreciate more business, the
already overburdened and underresourced psychiatric profession would not.
Lord Joffe in the UK proposes that courts or specialised tribunals should approve
assisted death requests. The danger is that lawyers will assume governance over
assisted dying, society will assume responsibility, and medical expertise and
involvement will be lost. This loss of medical input has occurred for a variety of
other reasons in obstetric care, psychotherapy and the management of suicide.
Lord Dawson of Penn, the eminent British physician, supported the defeat of
the 1936 Voluntary Euthanasia (Legalisation) Bill, believing euthanasia belonged
‘to the wisdom and conscience of the medical profession and not to the realm of
the law’.87 History has passed by such a view. Society and politics will determine
the legality of assisted dying. The euthanasia issue will not vanish from modern
society. Medicine and psychiatry need to start contributing to the debate rather
than merely dismissing euthanasia as wrong.
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CHAPTER 16
Psychopharmacology
MEDICINAL MATTERS
Essential psychotropic medications in palliative care
The young physician starts life with 20 drugs for each disease, and the old
physician ends life with one drug for 20 diseases.
Every doctor has pharmacological favourites and dislikes.2 A basic formulary of

relatively inexpensive oral and parenteral psychotropic medications for a ‘desert
island’ hospice might consist of:
➤ Opioid: morphine, methadone, naloxone
➤ Antidepressant: SSRI (escitalopram), tricylic (nortriptyline)
➤ Anxiolytic/hypnotic: midazolam, clonazepam
➤ Antipsychotic: haloperidol, levomepromazine
➤ Psychostimulant: methylphenidate
➤ Corticosteroid: dexamethasone.
The psychology of medicines

The psychology of medicines is not confined to pill-taking. Rectal administration
is acceptable to some but appals others. Transdermal delivery systems raise
credibility issues; patients are sometimes doubtful that they could be effective
and reliable. Continuous subcutaneous infusion (CSCI), via a syringe pump, is
increasingly the preferred delivery system toward the end of life when absorption
by the gut may be compromised or swallowing lost. Injectable medications
are assumed to be the more effective by many. However, with both CSCI
and transdermal delivery systems the physiological advantage may also be a
psychological disadvantage. Patients may resent the daily visit of the nurse to
231
refill the syringe (because of the reminders of how sick they are), or alternatively
be bereft by the absence of the nurse on the days a transdermal patch does not
need replacing. An attraction of complementary and alternative medicines
(CAM) is that they have not been scientifically evaluated, thus the practitioners
are able to advertise putative benefits (which haven’t been disproven) and
minimise disadvantages. A ‘neither-proven-nor-disproven’ medicinal status
is desirable. Users (and family members) share the belief of efficacy, usually
proposed to be consequent upon mind–body connection and good holistic
medicine.3 Aside from the potential for financial exploitation, adverse reactions
and interactions, CAM may cause significant psychological harm. CAM users,
when the treatment fails, are prone to hold themselves responsible for this failure,
adding psychological insult to an already failing physical state. The practitioners
blame the recipient of their potion, not their own skills or pills. Alternative health
practitioners take advantage of the placebo effect and deny the nocebo effect.
Placebo and nocebo responses

Placebo effects in clinical trials are typically substantial and often account
for a large proportion of the improvement attributed to the therapeutic agent
being tested. Though there is a large variation in the proportion of people who
will respond to a placebo it is possibly around 30%, with a suggestion that
placebos are getting more effective in recent times.4 Are our patients being
conditioned to respond to our drug treatments? It is difficult to identify likely
responders. Pain and mood are particularly sensitive to a placebo impact, and
physiological alterations in heart rate, blood pressure and muscle tone have been
demonstrated. How long these effects last is uncertain, though most benefits are
probably short-lived.4 There is good evidence for changes in neurotransmitter
levels, including serotonin and endogenous opioids, and functional imaging
and repetitive transcranial magnetic stimulation (rTMS) studies suggest the
involvement of prefrontal cortex and thalamic structures in the placebo effect.5,6
Expectation of effect, conditioning and learning are relevant mechanisms imply-
ing that both conscious and unconscious factors operate.7 The benefit of extra
attention afforded subjects participating in drug trials may result in more signifi-
cant placebo effects than in usual clinical practice. The general view is that the
therapeutic use of placebos is unethical in medical practice because it involves a
deception. Actually, hidden or secretive placebo administration is less effective
than openly providing a ‘dummy medication’.7 The principle of placebos causing
harm (the nocebo effect) has been long known by the practitioners of witchcraft
and voodoo. These can be induced by negative expectations related to previous
adverse reaction experiences, negative peer pressure or unsympathetic health-
care practitioners.4 Patient acceptance of the need for medication and even the
colour and size of the tablets can obliterate the placebo effect or contribute to
PSYCHOPHARMACOLOGY 233
non-pharmacological adverse effects. The art of prescribing requires consider-

able psychological skill.
Ethnic and cultural factors
The desire to take medicine is perhaps the greatest feature which distin-
guishes man from animals.
Pharmacologically, it does matter who one’s parents are (where your genes come
from) and how you live (the environmental influences moderating genes, e.g.
diet and exposure to various substances).9 Asians collectively represent 60% of
the world population though most drug-related knowledge and ‘evidence-base’
medicine has been established with Caucasian populations. Asians are often
treated successfully with lower doses of haloperidol and other antipsychotic
medications, though they have a greater prolactin response than Caucasians
and are more likely to experience extrapyramidal adverse effects. Effective lower
doses of antidepressants and benzodiazepines in Asians and rapid metabolising
of some Arabic and Ethiopian persons necessitating higher dosing of psycho
tropics suggests that stereotyping pharmacological responses is dangerous.
Ethnic variation exists in several of the CYP enzyme systems, particularly
CYP2D6. Dietary habits and smoking affect pharmacokinetics and genes exert
an influence on the therapeutic targets of psychotropic medications.9 Treatment
adherence may be influenced by many factors including culture, medical belief
systems, and linguistic misunderstandings. Culture and ethnicity are powerful
determinants of an individual’s response to psychopharmacology, as are inter-
individual variations within a defined cultural or ethnic group. Clinical wisdom
dictates a ‘start low, go slow’ approach to prescribing.
Pharmacokinetics in the dying
In all things there is a poison, and there is nothing without a poison. It

depends only upon the dose whether a poison is poison or not.
Paracelsus (1493–1541)10
The absorption, distribution, metabolism and excretion of drugs are affected by

genetic and disease factors. Gut transit times, route of administration, loss of
body mass, low albumin, dehydration, renal and hepatic failure may all influ-
ence pharmacokinetics. Smoking can reduce the blood concentrations of some
psychotropic medications by as much as 50%, by the induction of CYP1A2

enzymes leading to an increase in metabolism. Grapefruit juice can enhance the
blood concentrations of oral benzodiazepines. Drug interactions also affect drug
concentrations. ‘Start low, go slow’ and the reduction of drug dosages in terminal
illnesses are pharmacologically sensible clinical guidelines.
Swallowing medicine
Many patients have difficulties, both psychologically and physically, taking oral
medications. This may result in poor compliance and treatment failure. The
swallowing of capsules can be particularly difficult. Capsules are lighter than
water and float because of the air trapped inside the gelatinous shell. Tablets are
heavier than water and do not float. The usual method of swallowing oral solid
dose forms – putting it on the tongue, filling the mouth with water, tilting the
head back and swallowing, works well for tablets because gravity assists swal-
lowing. If this technique is followed with a capsule it will float on the water in
FIGURE 16.1 Head tilted back, capsule stuck.

the front of the mouth, placing it in the anatomically incorrect location for ease
of swallowing.11,12 A lean-forward technique is more effective for capsules.13
Patients require instruction, and ideally practise, to grasp this alternative
technique. This is particularly so for the elderly, the young, the cognitively com-
promised and the sick. Once learnt, the advantages rapidly reinforce the practice.
This is a technique that does not work for all but may be a viable option for those
patients in whom capsule swallowing is a problem.
Proprietary names
Generic medicinal names should routinely be used. The exception may be the
opioids. Internationally, the consensus appears to be to prescribe opioids by their
trade name. Many of the opioid preparations have similar names for varying
strengths – oxycodone could refer to both the short- and long-acting prepara-
tion – and much patient confusion can be generated. Perhaps this confusion has
been perpetrated by the pharmaceutical industry.
FIGURE 16.2 Head tilted forward, capsule ingested.

Blister packs
The advantages of such packaging to those with complex and multiple drug
regimes are obvious, particularly for the aged and infirm. However, such pack-
aging may remove the impetus to avoid polypharmacy and rationalise drug
therapy. In terminal illness health status can change precipitously and dangerous
overdosing may unwittingly occur. The rectification of a previously appropriate
regime is awkward and time-consuming for the doctor.
Drug stigmata
‘Morphine by another name’, opioids other than morphine may be acceptable
to those who associate morphine with addiction and/or impending death.
Methadone has connotations of abuse, for a major modern usage of it is for drug-
dependent persons. Similarly, antidepressants, antipsychotics and hypnotics have
fearful associations for some.
Prescribing outside usual regimes

Long-term adverse drug reactions are of little clinical relevance in palliative
medicine. Desperate symptoms may demand assertive dosing and the rapid
introduction of medicines. Alternatively, the frail ill may only require minuscule
doses of a medicine such as a tricyclic antidepressant to achieve a therapeutic
response. Firm pharmacological guidelines are inappropriate in this patient
population. Though no less care is required by the prescriber, certain prescrib-
ing liberties may be able to be taken with dosages, routes and indications in this
constrained setting.
Complementary and alternative medicine (CAM)

CAMs include acupuncture, massage, a variety of psychotherapies, transcutaneous
nerve stimulation as well as a cohort of medicines, including medicinal teas,
herbal, vitamin, nutritional, mineral, traditional and homeopathic therapies.
Between 30% and 50% of cancer patients in the Western world use a combination
of conventional and CAMs, rates which appear to be rising.14 At hospice admission
the most commonly used herbal medicines are St John’s wort, melatonin, ginkgo,
fish oil, kava, vitamin E, valerian, liquorice, ginseng, ginger, garlic and echinacea,
though this list is prone to fashion influences.15 Approximately 12% of the US
population take a herbal product, yet, of concern, only one-third report this to
their doctor.15 Compelling scientific proof of efficacy is lacking, and efficacy is
particularly difficult to establish in those who are drawn to these options as a
last, desperate resort. Polypharmacy is usual, hence the significant risk of drug
interactions.16 These are more likely in CAMs with psychotropic intent, such
as St John’s wort, which is prone to cause serotonin toxicity when unwittingly
combined with SSRIs or MAOIs (see Chapter 8 and Table 16.1). Herbal medicines
are prone to interactions via the CYP system or the transporter P-glycoprotein
and are mainly hepatically metabolised. In addition to the risks of hepatotoxicity,
nephrotoxicity and coagulating disorders traditional Chinese/herbal medicine
(TCM) can interact with anticonvulsants, benzodiazepines and opioids resulting
in a potentiation or diminution of therapeutic action.17
TABLE 16.1 Evidence-based possible major drug interactions.16
Evening primrose oil Warfarin, antiplatelet drugs

Ginkgo Warfarin, anticonvulsants
Kava CNS depressants
Hawthorn Digoxin, beta blockers, calcium channel blockers
Glucosamine Warfarin
St John’s wort Alprazolam, antidepressants, pethidine, tramadol, warfarin,
carbamazepine
Valerian Alprazolam, CNS depressants
ANTIDEPRESSANT ANOMALIES
Antidepressant jitteriness/anxiety syndrome
Many persons starting antidepressants, particularly those with prominent anxiety
symptoms, experience a transient worsening in anxiety, agitation and irritability.18
Typically, this activation occurs within days and resolves spontaneously within
days. This paradoxical reaction can be unsettling, frightening and dangerous for
suicidal ideation can be enhanced. Forewarning, and as required benzodiazepines,
may reduce the response to this effect, which is probably caused by a ‘tickling’
of the neurotransmitters, and is usually an indication of eventual therapeutic
responsiveness. It may occur with all the groups of antidepressants, but is
commoner (or reported more frequently) with the SSRIs.
Serotonin syndrome (serotonin toxicity)

Overstimulation of the serotonin receptors by large doses of a single pro-
serotonergic drug, or combinations of serotonergic agents (particularly if the
drugs act to increase serotonin by different mechanisms) may result in clinical
manifestations ranging from barely perceptible to lethal. Mental state changes
(delirium, agitation, restlessness, coma), autonomic signs (sweating, fever, tachy-
cardia, hypertension, diarrhoea, mydriasis, salivation) and neuromuscular effects
(hyperreflexia, hypertonia, myoclonus, ocular clonus, tremor, ataxia, rigidity)
may occur precipitously. Avoid combinations involving SSRIs, MAOIs, TCAs,
dopaminergic drugs, pethidine and tramadol, though the later is a theoretical
rather than an established risk (see Table 16.2). The differential diagnoses include
anticholinergic poisoning, neuroleptic malignant syndrome and malignant
hyperthermia. Discontinuation of the medicines and supportive measures (cool-

ing, controlling agitation and autonomic instability) usually results in prompt
resolution within 1–3 days, unless the offending agents have prolonged half-lives.
In severe cases intensive care management may be required. Benzodiazepines
to manage the agitation and serotonin antagonists such as cyproheptadine and
chlorpromazine may be administered. If a combination is essential the new drug
should be commenced at a very low dose and gradually titrated.
TABLE 16.2 Medications and the serotonin syndrome
Antidepressants (SSRIs, MAOIs, TCAs, SNRIs)

CNS stimulants (methylphenidate)
Opioids (tramadol, pethidine, fentanyl)
Lithium carbonate
Tramadol
St John’s wort
Amitriptyline
Amitriptyline is marginally more efficacious than other antidepressant
medications for major depressive disorder, but considerably more likely to cause
adverse effects.19 Its number needed to harm (NNH) is 7.4 and in the elderly
and frail these adversities include falls, postural hypotension, sedation, delirium
and constipation. Its sedative effect and analgesic action may be advantageous
in neuropathic pain patients, however the active metabolite of amitriptyline
is nortriptyline, which is very much more tolerable. Prescribing amitriptyline
should be discouraged. Nortriptyline and mirtazapine are preferable options.
Hyponatraemia
Hyponatraemia (serum sodium concentration of less than 136 mmol/L, though
symptoms rarely appear above 120 mmol/L) may be drug induced. Antidepressant
medications, particularly SSRIs, are probably the most frequent offender, and
usually ‘blamed’, though hyponatraemia is a common associate of most severe
medical illnesses and many medications. Thiazide diuretics, carbamazepine,
vinca alkaloids, cyclophosphamide, NSAIDs, and antipsychotic medications
may be causative, though most medications have been implicated. The elderly
are particularly at risk. Inappropriate antidiuretic hormone syndrome secondary
to cerebral disease and overzealous dosing of vasopressin need to be considered
in the differential diagnosis. Severe hyponatraemia may result in delirium and
coma. The withdrawal of the offending drug is advisable in conjunction with
fluid restriction and supportive measures. Mental recovery may take days to
weeks after the return to acceptable sodium levels.
Emotional side effects of SSRIs

Some persons experience a ‘blunting’ or ‘flattening’ of their emotions when taking
SSRIs.20 This is a robust statistically significant finding, though its prevalence has
not been determined. The restricted range of emotion tends to occur for positive
emotions such as happiness, enjoyment and passion, rather than for negative
ones. Emotional detachment, lack of caring and even personality change are also
reported, yet many appreciate the reduction of negative emotions (especially
early in the course of disease) and some experience the ‘blocking’ of emotional
lability as beneficial. The blunting tends to be noted once treatment has been well
established, rather than on initiation. It is difficult to determine if these effects
of SSRIs are primary symptoms of mood disturbance, or pharmacological or
psychological adverse effects. Compliance may become an issue, particularly
in those who dislike any semblance of loss of control or autonomy. For some
it may be a clinical indicator of treatment responsiveness and an appropriate
opportunity to consider withdrawal of the treatment.
Sexual side effects

Psychotropic medications, particularly SSRIs, commonly cause sexual
dysfunction, which is rarely reported spontaneously. Depressive illness and
systemic medical diseases may cause a loss of libido. Typically antidepressants
cause arousal and orgasmic disorders (erectile dysfunction, delayed/absence of
orgasm) in about half of those prescribed these medications.21 Terminal illness
does not always equate with the death of a sexual relationship.
ANTIPSYCHOTIC ECCENTRICITIES
The gut and psychotropic medications
There are a greater number of neurones in the gut than the brain. Psychotropic
medications are prone to induce gastrointestinal adverse effects including dry
mouth, constipation, diarrhoea and colic.
The subjective experience of taking antipsychotic medication

These medications are being used for an expanding variety of clinical indications
in non-psychotic persons: augmentation of antidepressant action, sedation,
analgesia, and antiemesis. In addition to their recognised adverse effect profile
they may produce a subjective state characterised by mental slowing and
emotional indifference.22 This is generally a most unpleasant and disagreeable
state of mind. Only 5% report a positive mental alteration such as calmness or
relaxation.22 The newer atypical antipsychotics may be more tolerable in this
regard and there is likely to be a dose correlation with the negative subjective
reactions. Neurological adverse effects further compound these psychiatric
adverse effects.
Antipsychotics, arrhythmias and stroke

Prolongation of the QTc interval resulting in serious ventricular arrhythmia and
sudden cardiac death is a risk of these medications, including the newer atypical
antipsychotics. The risk of cerebrovascular accidents is possibly enhanced with
ongoing use at higher dosage in the elderly. In palliative medicine these risks
may be relevant in the management of chronic nausea, though are relative risks
only in palliating delirium.
Akathisia
Akathisia is a subjective feeling of ‘inner’ restlessness and a drive to move. It
may be be particularly distressing. Desperation may be so severe that suicide
is considered.23,24 The motor restlessness is a response to the emotional distress
and to peripheral tactile hypersensitivity. The movements are semi-purposeful
and repetitive (e.g. pacing, fidgeting, difficulties sitting or standing, rocking, leg
swinging). In palliative medicine akathisia should be considered an emergency.
The prevalence in cancer patients may be as high as 5%.25 Akathisia may be
caused by typical and atypical antipsychotics, SSRIs, calcium channel blockers
and anti-emetics. It is often forgotten that anti-emetic medications, many of
which are phenothiazine derivatives, are a significant cause of akathisia in
cancer patients. High dosage and rapid dose escalation are risk factors as is a
history of psychiatric illness, particularly bipolar depression.26 The differential
diagnoses include restless legs syndrome, acute anxiety, dyskinesia, and drug
and psychotropic medication withdrawal states. Cessation of the drug and as
required anticholinergic agents are generally rapidly effective, sometimes within
minutes. Benzodiazepines may also be used with effect.
Oculogyric crisis/acute dystonia

These acute neurological adverse effects of high potency antipsychotic
medications are most frequently observed in young persons, and more likely
associated with phenothiazines and butyrophenones than the newer atypical
antipsychotics.27 It is a rare occurrence in the typical, older oncological patient.
It is often self-limiting but does respond promptly to anticholinergic medication
(e.g. benztropine) and/or benzodiazepines. It may be very frightening and
misnamed a ‘drug allergy’ by the suffering. Laryngeal dystonia can be fatal.
Neuroleptic malignant syndrome

This idiopathic reaction to dopamine antagonists tends to emerge slowly over
several days and cause bradykinesia, muscular rigidity, hyperthermia, autonomic
instability and delirium. It is potentially fatal. It can be difficult to differentiate
from serotonin toxicity. Management advice from an intensive-care physician
is advisable.
OPIOIDS AND OTHER ODDITIES

The pupillary effects of opioids
The miotic action of opioids is well recognised as a clinical indicator of
intoxication. This is contributed to by central sedative mechanisms though an
intact parasympathetic system is essential.28 It is blocked by opioid antagonists.
However, spontaneous minor oscillations of pupil size (‘hippus’) do occur,
including in those exposed to opioids. Tolerance to the pupillary effects has
been shown to occur,28 and in palliative medicine pupillary size is not a reliable
clinical sign of opioid toxicity.
Opioid pseudo-addiction and opioid recklessness

The appropriate titration of opioid doses requires skill. Sluggish or inadequate
increases foster pseudo-addictive behaviours (see Chapter 6). Generous dosing
may encourage misuse by the diversion of the quantity not required.
Benzodiazepine parsimony
Benzodiazepines, particularly the high potency, short-acting varieties, have had
much ‘bad press’ over recent decades. They are immensely valuable in palliative
medicine. They are versatile, well tolerated and effective but do require skill and
consideration in their use. Inducing ‘cognitive fog’ or emotional oblivion must
be avoided. Physiological dependency may be created by their use, but addiction
is an unlikely eventuality in the terminally ill.
Ceasing anticoagulants
The most difficult medicine to persuade patients to cease are the anticoagulants.
Prescribed for a sometimes visible, often painful, and invariably dangerous disor-
der most patients are petrified to contemplate their withdrawal. The interactions
of warfarin are many, and the risks of haemorrhage are significant. But a sudden,
dramatic death is not necessarily welcomed either.
REFERENCES
1 Quoted in: Hughes G. Aequanimitas. Emerg Med J. 2009; 26: 314.
2 De Lima L, Krakauer EL, Lorenz K, et al. Ensuring palliative medicine availability: the
development of the IAHPC list of essential medicines for palliative care. J Pain Symp
Manage. 2007; 33: 521–6.
3 Eliott JA, Kealey CP, Olver IN. (Using) complementary and alternative medicine: the
perceptions of palliative patients with cancer. J Palliat Med. 2008; 11: 58–67.
4 Edwards R, Graedon J, Graedon T. Placebo harm. Drug Saf. 2010; 33: 439–41.
5 Mayberg H, Silva JA, Brannan SK, et al. The functional neuroanatomy of the placebo
effect. Am J Psychiatry. 2002; 159: 728–37.
6 Benedetti F. No prefrontal control, no placebo response (commentary). Pain. 2010;
148: 357–8.
7 Benedetti F. Recent advances in placebo research. Int J Pain Med Palliat Care. 2005; 4:
2–7.
8 Cushing H. The Life of Sir William Osler, Vol. 2. London: Oxford University Press; (1925)
1940. p. 342.
9 Chen C-H, Chen C-Y, Lin K-m. Ethnopsychopharmacology. Int Rev Psychiatry. 2008;
20: 452–9.
10 Jacobi J. Paracelsus: Selected Writings. Princeton, NJ: Princeton University Press; 1998.
p. 95.
11 Brown JA. Swallowing medication (letter). JAMA. 1882; 248: 1833–4.
12 Kahn G. Capsule swallowing: the lean-forward technique. Cutis. 1985; 36: 144.
13 Macleod AD, Vella-Brincat J, Frampton C. Swallowing capsules. Palliative Medicine.
2003; 17: 559.
14 Molassiotis A, Fernadez-Ortega P, Pud D, et al. Use of complementary and alternative
medicine in cancer patients: a European study. Ann Oncol. 2005; 16: 655–63.
15 Holmes HM, Kaiser K, Jackson S, et al. Soliciting an herbal medicine and supplement
use history at hospice admission. J Palliat Med. 2010; 13: 685–94.
16 Moses GM, McGuire TM. Drug interactions with complementary medicines. Australian
Prescriber. 2010; 33: 177–80.
17 Chiu J, Yau T, Epstein RJ. Complications of traditional Chinese/herbal medicines
(TCM) – a guide for perplexed oncologists and other cancer caregivers. Support Care
Cancer. 2009; 17: 231–40.
18 Sinclair LI, Christmas DM, Hood SD, et al. Antidepressant-induced jitteriness/anxiety
syndrome: systematic review. Brit J Psychiatry. 2009; 194: 483–90.
19 Thompson C. Amitriptyline: still efficacious, but at what cost? Brit J Psychiatry. 2001;
178: 99–100.
20 Price J, Cole V, Goodwin GM. Emotional side-effects of selective reuptake inhibitors:
qualitative study. Brit J Psychiatry. 2009; 195: 211–17.
21 Schweitzer I, Maguire K, Ng C. Sexual side-effects of contemporary antidepressants: a
review. Aust NZ J Psychiatry. 2009; 43: 795–808.
22 Moncrieff J, Cohen D, Mason JP. The subjective experience of taking antipsychotic
medication: a content analysis of internet data. Acta Psychiatr Scand. 2009; 120: 102–11.
23 Poyurovsky M. Acute antipsychotic-induced akathisia revisited. Br J Psychiatry. 2010;
196: 89–91.
24 Chow LY, Chung D, Leung V, et al. Suicide attempt due to metoclopramide-induced
akathisia. Int J Clin Pract. 1997; 51: 330–1.
25 Kawanishi C, Onishi H, Kato D, et al. Unexpectedly high prevalence of akathisia in
cancer patients. Palliat & Support Care. 2007; 5: 351–4.
26 Kumar R, Sachdev PS. Akathisia and second-generation antipsychotic drugs. Curr Opin
Psychiatry. 2009; 22: 293–9.
27 Satterthwaite TD, Wolf DH, Rosenheck RA, et al. A meta-analysis of the risk of acute
extrapyramidal symptoms with intramuscular antipsychotics for the treatment of agita-
tion. J Clin Psychiatry. 2008; 69: 1869–79.
28 Murray RB, Adler MW, Korczyn AD. The pupillary effects of opioids. Life Sci. 1983; 33:
495–509.
The Psychiatry of

Palliative Medicine
  
Second Edition
This Second Edition of The Psychiatry of Palliative Medicine remains a practical and
pragmatic distillation of the psychiatry relevant to the terminally ill. Revised throughout
and greatly expanded by the addition of two entirely new chapters, it reviews the major
psychiatric syndromes encountered in palliative care – depression, anxiety, delirium
– and examines psychopharmacological and psychological interventions in detail. It
succinctly considers the psychiatric aspects of pain, sleep, cognitive impairment, terminal
The Psychiatry of
Palliative Medicine
neurodegenerative diseases, sedation, artificial feeding and euthanasia. The dying,
chronically ill psychiatric patient is also discussed.
The author has drawn on his great experience in both consultation–liaison psychiatry
and palliative medicine to produce an essential, evidence-based guide for all healthcare
professionals involved in palliative care. These include consultants and senior nurses, as
well as psychiatrists, especially consultation–liaison psychiatrists, and trainees.
  
‘I find this an immensely sympathetic book, beautifully written. It is a testimony to the Second Edition
  

summation of specialist psychiatric knowledge, broad scholarship and a rich personal practice
in bedside palliation.’ From the Foreword by Ian Maddocks
AD (Sandy) Macleod
    
‘...a relevant, highly readable and reasonably priced book which will be of interest to all,
whether from a psychiatric or palliative care background, who seek to improve the care of
dying patients.’    
International Psychogeriatrics
‘Practical, scientifically based and scholarly, addressing a comprehensive set of common and
Second Edition AD (Sandy) Macleod

important clinical problems in palliative care. The book will doubtlessly be highly valued
by palliative care clinicians for its practical and thorough overview of some of the most
challenging clinical problems they face. Excellent and timely.’
Australian and New Zealand Journal of Psychiatry
    

Counselling for Death and Dying Practical Psychiatry of Old Age
Person-centred dialogues Fourth Edition
Richard Bryant-Jefferies John P Wattis and Stephen Curran
ISBN 978-1-84619-535-8
www.radcliffepublishing.com
Electronic catalogue and

worldwide online ordering facility.
9 781846 195358
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The Psychiatry of

  

Second Edition AD (Sandy) Macleod

    

Electronic catalogue and

macleod_9781846195358_pb.indd 1 25/5/11 10:20:34

© 2011 by Sandy Macleod

No claim to original U.S. Government works

International Standard Book Number-13: 978-1-138-03151-7 (eBook - PDF)

Visit the Taylor & Francis Web site at

and the CRC Press Web site

Foreword to the second edition vi

1 Psychiatry and palliative medicine 1

This is a book for clinicians, written by a clinician practising both psychiatry

Associate Professor Sandy Macleod graduated from the University of Otago

Psychiatry and palliative medicine

It is the special vocation of the doctor to grow familiar with suffering.

John Greenleaf Whittier (1807–92)1

The cardinal goal of medical care is to alleviate suffering. Suffering is an unpleas-

history provides the information on which diagnostic hypotheses are formulated.

Psychodynamic conceptualisation is less emphasised. There is a considerable

Adjustment and anxiety

ADJUSTMENT DISORDER (OR DISTRESS)

William Osler (1849–1919)3

The Diagnostic and Statistical Manual of Mental Disorders (DSM) IV and

and permit financial return to health professions. By DSM definition, within

distress and indecision of the individual. A fundamental and reassuring task of

FRIGHT, FEAR AND ANXIETY

Benjamin Rush (1746–1813)11

A sudden, unexpected sensory stimulus may result in fright, a pre-emotional,

BOX 2.1 Symptoms of anxiety

Psychological: apprehension, panic, inappropriate fear, foreboding, dread,

nausea, dysphagia (‘globus hystericus’)

● respiratory: hyperventilation (‘air hunger’), yawning, sighing

● nervous system: headaches, dizziness, tremor, paraesthesia, shakiness,

muscle twitching, restlessness

● dermatological: sweating, rash.

It is faere [fear] I stand most in faere [fear] of.

Dependence and addiction

Apart from dependency, there is no evidence of psychiatric morbidity caused by

advocated. Combination with alcohol amplifies the risks of neuropsychiatric

POST-TRAUMATIC ANXIETY STATES

diagnosis. The probability of evolving PTSD is dependent on the type of trauma

BOX 2.2 Post-traumatic stress disorder

Exposure to a traumatic event: involving the perception of life being threatened.

traumatic event, recurring distressing dreams and nightmares, dissociative

startle reflex, irritability, angry outbursts, poor concentration, safety

Duration: acute <3 months, chronic >3 months.

Cancer, particularly at the time of diagnosis, can induce post- traumatic

and extreme sun exposure, is interpreted by most as ‘fate’ or misfortune. An

John Locke (1632–1704)49

Psychological development, maturation and ‘growth’ can be precipitated by

HM, Brietbart W, editors. Handbook of Psychiatry in Palliative Medicine. Oxford:

Psychological issues and dying

Bodies devoid of mind are as statues in the market place.

Euripides (484–406 BC)1

Much has been written of psychology as it relates to cancer. Putative psychologi-

PSYCHOLOGICAL RESPONSES TO ILLNESS

TABLE 3.1 Personality and illness (adapted from reference 2)

Personality Personality characteristics Meaning of illness Countertransference Management

TABLE 3.2 Ego defence mechanism (adapted from reference 3)

Defence type Characteristics Consequences