PERSPECTIVES

Psycho-Oncology

William S. Breitbart, MD, and Yesne Alici, MD

The psychosocial and psychiatric sequelae of cancer are highly prevalent, diverse, and challenging
for clinicians to manage. A growing body of literature has generated methods for the reliable screen-
ing, assessment, and management of these sequelae, including the treatment of psychiatric disorders
that may complicate the course of cancer. To meet the specific needs of this patient population,
psycho-oncologists worldwide have begun to train more and more social workers, psychologists,
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and psychiatrists who can provide consultative services in support of the psychiatric care of can-
cer patients and their families at all stages of disease, including cancer survivorship. This review
presents an overview of the history of psycho-oncology, common psychological responses to cancer,
factors in adapting to cancer, epidemiology, the assessment and management of major psychiatric
disorders in cancer patients, cancer-related fatigue, the cognitive effects of cancer and cancer treat-
ment, issues related to the psychosocial care of families (including bereavement), and psychological
issues for staff caring for cancer patients. (HARV REV PSYCHIATRY 2009;17:361–376.)
For personal use only.

Keywords: psychiatric care of cancer patients, psycho-oncology, psychosocial care of cancer

patients

Psycho-oncology, or the study and practice of the psy-
chological and psychiatric aspects of cancer, is an expand-
ing field that addresses the psychological response to can-
cer of patients, their families, and clinicians, as well as the
psychological, behavioral, and social factors that influence
From the Department of Psychiatry, Weill Medical College of
Cornell University (Dr. Breitbart); Psychiatry Service, Department
of Psychiatry and Behavioral Sciences, and Pain and Palliative Care
Service, Department of Neurology, Memorial Sloan-Kettering Can-
cer Center, New York, NY (Dr. Breitbart); Geriatric Services Unit,
Central Regional Hospital, Butner, NC (Dr. Alici)
Original manuscript received 4 April 2009; accepted for publication
subject to revision 12 August 2009, revised manuscript received 15
October 2009.
Correspondence: Yesne Alici, MD, Geriatric Services Unit, Cen-
tral Regional Hospital, 300 Veasey Rd., Butner, NC 27509. Email:
yesnea@yahoo.com


c 2009 President and Fellows of Harvard College
DOI: 10.3109/10673220903465700
cancer risk, detection, and survival.1–3 The field comprises
clinicians and researchers throughout the world, who are
represented by national, as well as international, organi-
zations. Several psycho-oncology training programs have
been established in recent years. Most cancer centers have
specified one or more clinicians as responsible for provid-
ing psychosocial support and consultation to patients and
families, and liaison services to oncology teams.2,3 When
interdisciplinary psycho-oncology teams are in place, they
typically include clinicians and researchers from psychi-
atry, psychology, social work, nursing, and the clergy. To
improve effective communication in the care of cancer pa-
tients, communication-skills training programs have been
developed for clinicians.4 Based on evidence from existing
research, clinical practice guidelines on psychiatric assess-
ment and management of cancer patients have also been
established.5 Several survivor programs offering workshops,
lectures, and support groups are available to patients and
families worldwide, informed by research efforts to improve
quality of life among cancer survivors.5,6
The amount and variety of research in psycho-oncology
is, indeed, rapidly growing and includes studies looking
at the role of social, psychological, and behavioral fac-
tors in cancer prevention, early detection, and survival,
as well as studies exploring the impact of therapeutic

361

362 Breitbart and Alici
interventions on quality of life and patient-reported
outcomes.7 Research examining the mechanism of cy-
tokines in producing “cytokine-induced sickness behavior”
may provide a biological basis and advanced treatment
options for symptom clusters of fatigue, depression, anxiety,
and cognitive changes in cancer patients.8,9 Research on
“chemobrain” has gained momentum, particularly with
recognition of the specific needs of growing numbers of
aging cancer patients.10–12 Novel psychotherapy modalities
(e.g., meaning-centered psychotherapy, mindfulness-based
stress-reduction programs, and cognitive-existential, as
well as supportive-expressive, group therapies) are actively
being developed and studied in cancer patients, thereby
enriching the armamentarium of psychosocial interventions
effective in this patient population.13–17
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This review article intends to present an overview of the
historical background, common psychological responses to
cancer, factors influencing adaptation to cancer, major psy-
chiatric disorders in cancer patients, cancer-related fatigue,
cognitive effects of cancer and cancer treatment, issues re-
lated to the psychosocial care of families (including bereave-
ment), and psychological issues for clinicians caring for
For personal use only.
cancer patients.
PSYCHO-ONCOLOGY: GENERAL
CONSIDERATIONS
Historical Background
Psycho-oncology has emerged slowly since the 1970s as a
subspecialty within oncology and also within psychiatry
and psychosomatic medicine.1 With increasing numbers of
patients and families informed of cancer diagnoses, grow-
ing emphasis on improvement of palliative care and pain
management, and increasing recognition of the importance
of quality of life, patient-reported outcomes, and patients’
rights, the need for supportive, psychologically oriented can-
cer care has become more pronounced. In the 1980s psycho-
oncology units began to develop in larger cancer centers.1
Early on, prevalence studies of psychiatric and psycholog-
ical sequelae in cancer were reported.18 In the 1990s, be-
havioral research on modifying habits (such as smoking),
diet, and lifestyle led to improved public education on can-
cer prevention.1 Health-related quality-of-life assessments
and, more recently, patient-reported outcomes have now be-
come standard outcome measures in clinical trials.5 Nev-
ertheless, though psycho-oncology continues to grow in so
many dimensions, historical attitudes toward cancer con-
tinue to undercut patients’ and families’ willingness to iden-
tify and verbalize their emotional problems, especially in un-
derserved populations, different cultures, and various parts
of the world.1
Harv Rev Psychiatry
November/December 2009
Common Psychological Responses to Cancer
The diagnosis of cancer requires patients, despite their own
distress, to adapt quickly to catastrophic news. In addition
to the fear of death, major concerns include potential depen-
dency, disfigurement, pain, disability, and abandonment, as
well as disruptions in relationships, role functioning, and
financial status.2,7 Patients show an initial, characteristic
response of shock and denial, the duration of which depends
on the patient, diagnostic workup required, prognosis, time
to the initiation of cancer treatment, and potential compli-
cations of treatment.21 Patients try to control their levels
of emotional distress while making crucial treatment de-
cisions. The presence of a relative or friend can help with
the processing of important information in this phase. Re-
search has shown that the way in which news is delivered by
clinicians early in diagnosis can influence a patient’s beliefs
and attitudes toward future treatment and medical staff.
Guidelines and recommendations are available on how to
communicate the diagnosis, treatment plan, and prognosis
to cancer patients.2,4,7,19 Workshops in developing commu-
nications skills for clinician-educators have been utilized
successfully in major cancer centers.4 The second phase of
response to diagnosis is characterized by a period of emo-
tional turmoil, with mixed symptoms of anxiety and depres-
sion, irritability, insomnia, poor concentration, and inability
to function. These symptoms usually begin to resolve with
support from family, friends, and the physician who out-
lines a treatment plan. This phase usually lasts one to two
weeks.2 During the third phase, the patient adapts to the
diagnosis and treatment, and returns to previously used
coping strategies that are helpful in reducing stress.3
Factors in Adapting to Cancer
Patient responses are modulated by factors relating to the
particular society, the individual patient, and the cancer
itself.2,3 Social factors reflect the larger society’s attitudes
toward cancer and cancer treatment, as well as current
knowledge and perceptions of cancer. The legal requirement
of informed consent has improved communication between
physicians and patients about illness, treatment options,
and prognosis.7 For some patients, however, this additional
information creates an additional burden because of their
awareness of the severity of their illness.7 Many patients
and families are influenced, too, by the belief that stress,
grief, depression, or certain types of personality traits can
cause cancer, even though various studies have demon-
strated that depression, personality, and grief do not in-
crease the risk of cancer.7,20–25 That said, intriguing find-
ings from psychoneuroimmunology studies suggest a link
between depression, impairment of the immune system, and
 Harv Rev Psychiatry
Volume 17, Number 6
certain cancer types such as lymphoma. These results war-
rant further study.7,25
The individual factors that modulate adaptation to can-
cer are intrapersonal, interpersonal, and socioeconomic in
character. The intrapersonal factors include preexisting per-
sonality style, coping ability, ego strength, developmental
stage, the impact and meaning of the cancer at that stage
of life,3,26 the level of social support obtained from family,
friends, and others, and socioeconomic status. Lower socioe-
conomic status, in particular, has been shown to be a poten-
tial barrier to access health care.27
Adaption to cancer is, finally, related to the charac-
teristics of the disease itself, such as disease stage, site,
prognosis, symptoms (including pain), type of treatment,
and impact (of both the disease and the treatment) on
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functionality.3,7
An understanding of the factors that predict ineffective
adjustment to cancer at different stages of disease and treat-
ment enables early identification and intervention for vul-
nerable individuals.
Epidemiology of Psychiatric Disorders in Cancer Patients
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The prevalence of psychiatric disorders in cancer patients
is approximately 50%,5,18,28 and most of these disturbances
relate to the cancer itself or cancer treatment. The preva-
lence is highest among patients with advanced disease and
poor prognosis.7,18,28–30 More than two-thirds of psychiatric
disorders in cancer patients represent adjustment disor-
ders; 10% to 15%, major depressive disorder (based on the
DSM-III definition); and about 10%, delirium.18,28 Inpatient
studies show a higher incidence of both depression (20% to
45%)∗ and delirium (rising from 15% to 75% with advancing
disease).18,28–30 Unfortunately, highly prevalent disorders
that are potentially treatable—such as major depression
and delirium—continue to be underdiagnosed and under-
treated among cancer patients.5,28–31
ASSESSMENT AND MANAGEMENT OF COMMON
PSYCHIATRIC DISORDERS IN PATIENTS WITH
CANCER
The Panel for Management of Psychosocial Distress, ap-
pointed by the National Comprehensive Cancer Network,
has developed guidelines to assist oncology teams in rapidly
∗
In caring for cancer patients, it is difficult to clearly make the
diagnostic distinctions among different depressive disorders based
on the DSM-IV. This difficulty has led to great confusion in the
psycho-oncology literature. Throughout this review, unless specified
as “major depressive disorder,” depression refers to any depressive
disorder.
Psycho-Oncology 363
screening and identifying patients with distress.5 The panel
proposed use of the term “distress” because of the stigma
among patients, families, and health care providers for
terms such as “psychiatric” or “psychological” problems.
The panel has developed a simple “Distress Thermometer,”
where patients are asked to rate their levels of distress on a
scale of 0 to 10. The thermometer is accompanied by a list of
the major sources of distress—namely, physical, psycholog-
ical, social, spiritual, or practical (e.g., financial) problems.
Widespread use of this scale in outpatient settings facili-
tates the integration of psychosocial and psychiatric coun-
seling into the total care of cancer patients.3,5,32
The psychiatric assessment of cancer patients involves
a thorough medical evaluation of cancer site, stage, treat-
ment, and any associated medical conditions or treatments;
a comprehensive assessment of the patient’s past psychi-
atric history, current mental state, and understanding of
his or her illness and prognosis; and an assessment of
the patient’s social and spiritual support systems.2,5,7 The
physician should also address the family and the family-
staff interface, and must remain actively involved in the
patient’s care through all stages of the illness, including
initial diagnosis, remission, recurrence, or progression of
cancer.7
The optimal psychiatric treatment of cancer pa-
tients requires the simultaneous use of multiple
modalities—ranging from psychotherapy to medication, and
anything, as necessary, in between—in an attempt to re-
lieve distressing symptoms such as depression, fatigue, and
anxiety.7
Numerous psychotherapy modalities—including
cognitive-behavioral therapy (CBT), crisis intervention,
problem-solving techniques, supportive psychotherapy,
and group psychotherapy—have been found effective in
reducing distress and improving overall quality of life
among cancer patients.17,33
CBT, which utilizes relaxation techniques and problem-
solving skills to reduce distress, also helps patients to iden-
tify and correct dysfunctional thoughts that lead to anxiety,
depression, or other forms of distress. It has been proven
to be effective in alleviating distressing psychological and
physical symptoms in cancer patients.5,34,35
Behavioral techniques, such as hypnosis, relaxation, de-
sensitization, and distraction, are useful in a wide range
of situations in oncology, including: relief of anxiety related
to surgical procedures; relief or prevention of conditioned
symptoms, such as anticipatory nausea and vomiting asso-
ciated with chemotherapy; and, more broadly, management
of symptoms in children.7
Different forms of group psychotherapy have been ex-
tensively evaluated among cancer patients. The impact
of group psychotherapy on improved quality of life, cop-
ing skills, self-esteem, pain management, and interper-
sonal relations in this population is well supported by

364 Breitbart and Alici
several studies.14 Supportive-expressive group therapy im-
proves psychological symptoms, pain, and overall quality of
life in patients with metastatic breast cancer.36 Cognitive-
existential group therapy reduces psychological distress
among women with early-stage breast cancer receiving adju-
vant chemotherapy.37 Meaning-centered group psychother-
apy, a novel group psychotherapy modality designed to help
patients with advanced cancer to sustain or enhance a sense
of meaning as they approach the end of life, is effective in
reducing distress in that patient population.15
In the following subsections we will briefly review the as-
sessment and management of common psychiatric disorders
in cancer patients.
Delirium
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Delirium, a common and often serious neuropsychiatric
complication in managing cancer patients, is characterized
by an abrupt onset of disturbances of consciousness, at-
tention, cognition, and perception that tend to fluctuate
over the course of the day, precipitated by an underly-
ing medical condition.38 Delirium is a medical emergency
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that needs to be identified and treated vigorously. Unfortu-
nately, it is frequently undiagnosed and untreated in can-
cer patients—which increases morbidity and mortality, in-
terferes in the management of symptoms such as pain,
increases the length of hospitalizations, generates higher
health care costs, and increases distress for patients, fami-
lies, and caregivers.30,31,39–42
Delirium is present in 25% to 85% of cancer patients, de-
pending on the stage of illness.30,31,39,40,42 Prevalence rates
of delirium range from 15% to 30% in hospitalized cancer
patients.31,41 It is highly prevalent in the last weeks of life,
ranging from 40% to 85%.30,31 Predisposing factors for de-
veloping delirium during hospitalization include old age, de-
mentia, functional impairment, and the nature and severity
of the illness.31,41,43–45
In patients with advanced cancer, delirium can be due
to either the direct effects of cancer on the central ner-
vous system or the indirect CNS effects of the disease or
treatments (e.g., medications, electrolyte imbalance, major
organ failure, infection, or paraneoplastic syndromes).30,41
The diagnostic workup of delirium should focus on assess-
ing the potentially reversible etiologies, such as dehydra-
tion or those relating to the use of particular medications,
as well as those that are potentially irreversible, such as
sepsis or major organ failure. Medications such as opioids,
benzodiazepines, and anticholinergics are common causes
of delirium, particularly in the elderly and the terminally
ill.5,46,47 Chemotherapeutic agents known to cause delirium
include ifosfamide, methotrexate, fluorouracil, vincristine,
vinblastine, bleomycin, carmustine, cis-platinum, asparag-
inase, procarbazine, and glucocorticosteroids.46 When as-
Harv Rev Psychiatry
November/December 2009
sessing etiologies of delirium in terminally ill cancer pa-
tients, an important challenge is the clinical differentiation
of delirium as either a reversible complication of cancer or its
treatment, or an integral element of the dying process. The
potential utility of a thorough diagnostic assessment has
been demonstrated in patients with advanced cancer.31,43–45
The diagnostic gold standard for delirium is the clin-
ician’s assessment utilizing the DSM-IV-TR criteria.38,41
Delirium is classified into three clinical subtypes, based on
arousal disturbance and psychomotor behavior, including
the hyperactive, the hypoactive, and the mixed subtype.48
Approximately two-thirds of all deliriums are of the hypoac-
tive or mixed subtype.48 In the palliative care settings, hy-
poactive delirium is most common.49 Evidence suggests that
the subtypes of delirium may be related to different causes
and may have different treatment responses and different
prognoses.31,48,50,51
In hospitalized cancer patients, many of the clinical fea-
tures of delirium can also be associated with other psychi-
atric disorders such as depression, mania, psychosis, and
dementia. Delirium, particularly the hypoactive subtype, is
often initially misdiagnosed as depression. In distinguish-
ing delirium from depression, particularly in the context of
advanced cancer, an evaluation of the onset and temporal
sequencing of symptoms is especially important.41,46
Although a past psychiatric history or a family history of
depression increases an individual’s risk of developing de-
pression, delirium is a likely diagnosis in the presence of an
acute onset, fluctuating course of disturbances of cognition
and consciousness with one or more medical etiologies.31
Various screening and evaluation tools have been devel-
oped to maximize diagnostic precision and to assess delir-
ium severity. The commonly used delirium scales are the
Delirium Rating Scale–Revised 98, the Memorial Delirium
Assessment Scale (MDAS), and the Confusion Assessment
Method (CAM).52–57 The MDAS is a ten-item delirium
screening and assessment tool, validated among hospital-
ized patients with advanced cancer and AIDS.54 A cutoff
score of 13 is diagnostic of delirium. The MDAS has been
revalidated among advanced cancer patients in inpatient
palliative care settings with a sensitivity of 98% and a speci-
ficity of 96% at a cutoff score of 7.55 The CAM is a nine-item
delirium diagnostic scale based on the DSM-III-R criteria
for delirium.56 It has recently been validated in palliative
care settings with a sensitivity of 88% and a specificity of
100% when administered by well-trained clinicians.57
The standard approach to managing delirium in can-
cer patients, even in those with advanced disease, in-
cludes a search for underlying causes, correction of those
factors, and managing the symptoms with pharmacologic
and nonpharmacologic interventions.31,41 In the terminally
ill patient who develops delirium in the last days of life,
the management of delirium is unique, requiring difficult
 Harv Rev Psychiatry
Volume 17, Number 6
judgments that revolve around the setting of care, extent
of diagnostic assessment, and appropriate interventions. In
most cases, the goals of care are significantly altered by the
dying process.31
Nonpharmacologic approaches play an essential role in
the treatment of cancer patients with delirium, particu-
larly in the terminally ill.30 Studies in the medically ill
show that nonpharmacologic interventions, compared to
usual care, result in faster improvement of delirium and
slower deterioration in cognition, without any beneficial ef-
fects on mortality or health-related quality of life.58,59 Non-
pharmacologic interventions include oxygen delivery, fluid
and electrolyte administration, ensuring bowel and blad-
der function, nutrition, mobilization, pain treatment, fre-
quent orientation, use of visual and hearing aids, and en-
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vironmental modifications (e.g., quiet, well-lit room with
familiar objects, and a visible clock or calendar) to en-
hance a sense of familiarity.30,58,59 Nonpharmacologic in-
terventions alone are often not effective in controlling
the symptoms of delirium, and pharmacologic treatment
is necessary in most cases.46 Antipsychotics constitute
the primary pharmacologic intervention (Table 1).41 The
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American Psychiatric Association practice guidelines pro-
vide directions for using antipsychotics in the treatment
of delirium; a growing body of evidence supports their
use.
Due to its efficacy and safety, haloperidol is taken to be
the gold-standard medication for treating delirium in can-
cer patients safely.41 Due to their favorable side-effect pro-
file, atypical antipsychotics—namely, aripiprazole, olanza-
pine, quetiapine, risperidone, and ziprasidone—are being
increasingly used to treat delirium.31,60–63 None of the an-
tipsychotic medications has been approved by the U.S. Food
and Drug Administration (FDA) for treating delirium in can-
cer patients. Most studies are limited to open-label trials,
case reports, and retrospective reviews. Comparison trials
have not identified any antipsychotic medication as supe-
rior to another in terms of efficacy;60–63 further research is
needed to assess both efficacy and safety. The choice of med-
ication for treating delirium in cancer patients depends on
multiple factors, including the degree of agitation, subtype
of delirium, the available route of administration, and con-
current medical conditions.31,60 A recent Cochrane review
on drug therapy for delirium in the terminally ill concluded
that, based on a double-blind, randomized, controlled study,
haloperidol was the most suitable medication for treating
patients with delirium near the end of life, and that chlor-
promazine was an acceptable alternative as long as the
small risk of cognitive impairment was not a concern.63
Due to the small number of patients (n = 30) in that same
study, however, the evidence remains insufficient to draw
any conclusions regarding the role of pharmacotherapy in
terminal delirium.50,63 A different review, which compared
Psycho-Oncology 365
the efficacy and the incidence of adverse effects between
haloperidol and atypical antipsychotics, concluded that
haloperidol and selected newer atypical antipsychotics
(olanzapine and risperidone) were effective in managing
the symptoms of delirium, with comparable side-effect
profiles.62
The FDA has recently released a public health advisory
on the increased risk of death associated with using an-
tipsychotics to treat the behavioral disturbances of patients
with dementia.64,65 It is not known whether these warn-
ings apply to short-term use (i.e., one to two weeks) of an-
tipsychotics to treat delirium in patients with cancer. The
FDA has recently issued another warning about the risk
of QT prolongation and torsades de pointes when using
intravenous haloperidol; electrocardiogram monitoring for
QT prolongation has therefore become standard practice in
such situations.66 While clinicians should attempt to use low
doses, especially when treating elderly cancer patients with
delirium, leaving delirium untreated may impose a greater
risk of morbidity and mortality.
Some clinicians have suggested that the hypoactive sub-
type of delirium may respond to psychostimulants such
as methylphenidate or to combinations of antipsychotics
and psychostimulants.67–70 At best, however, the evidence
for using psychostimulants to treat hypoactive delirium is
limited,68,70 and the risks of precipitating agitation and ex-
acerbating psychotic symptoms should be carefully evalu-
ated before using psychostimulants to treat delirium in can-
cer patients.
As highlighted in this section, psychiatrists commonly
encounter delirium as a major complication of cancer and
its treatments, particularly among hospitalized cancer pa-
tients. Proper assessment, diagnosis, and management of
delirium are essential in improving quality of life and min-
imizing morbidity in cancer patients.
Anxiety Disorders
Anxiety is the most common psychological response in the
setting of a cancer diagnosis. Though a normal adaptive re-
sponse to a threat, anxiety can become maladaptive, impair
functioning, and interfere with the care of cancer patients.
The prevalence of anxiety disorders in cancer patients is
generally reported to be in the 10%–30% range, but the cur-
rent prevalence data are unreliable due to the use of differ-
ent scales for diagnosing anxiety, lack of prospective data,
and small sample sizes.71
The main clinical features and assessment of the anxi-
ety disorders commonly encountered in cancer patients are
reviewed below.
Adjustment disorders with anxiety. Adjustment disorders
with anxiety or depressed mood represent the largest group
 Harv Rev Psychiatry
366 Breitbart and Alici November/December 2009

Table 1. Antipsychotic Medications in the Treatment of Delirium in Cancer Patients

Routes of
Medication Dose range administration Side effects Comments

Typical antipsychotics
Chlorpromazine
Haloperidol
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12.5–50 mg every PO, IV, IM, SC, PR More sedating and May be preferred in
4–6 hours anticholinergic than agitated patients due to
haloperidol; monitor its sedative effect
blood pressure for
hypotension
0.5–2 mg every PO, IV, IM, SC Monitor for Gold standard for
2–12 hours extrapyramidal side delirium; may add
effects, QT interval on lorazepam (0.5–1 mg
EKG every 2–4 hours) for
agitated patients

Atypical antipsychotics
Aripiprazole
Olanzapine
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5–30 mg every PO,a IM Monitor for akathisia Evidence is limited to case
24 hours reports and case series
2.5–5 mg every PO,a IM Sedation is the main Older age, baseline
12–24 hours dose-limiting adverse cognitive deficits, and
effect in short-term use hypoactive subtype of
delirium have been
associated with poor

response
Quetiapine 12.5–100 mg every PO Sedation, orthostatic Sedating effects may be
12–24 hours hypotension helpful in patients with
sleep-wake cycle
disturbances
Risperidone 0.25–1 mg every POa Extrapyramidal side Clinical experience
12–24 hours effects can occur, suggests possibly better
particularly with doses results in patients with
>6 mg/day; orthostatic hypoactive delirium
hypotension
Ziprasidone 10–40 mg every PO, IM Monitor QT interval on Evidence is limited to case
12–24 hours EKG reports

IM, intramuscular; IV, intravenous; PC, rectal; PO, oral; SC, subcutaneous.
a
Risperidone, olanzapine, and aripiprazole are available in orally disintegrating tablets.

of Axis I diagnoses found in cancer patients.38,72 The car-
dinal features of the adjustment disorder diagnostic cat-
egory are clinically significant emotional or behavioral
symptoms (in excess of what might be expected) or social
impairment that develops within three months of an iden-
tifiable stressor, and resolution of these symptoms within
six months of termination of the stressful trigger.38 Clini-
cally, the symptoms of an adjustment disorder with anxiety
are similar to generalized anxiety, with the caveat that pre-
sumably without the stressor, the patient would not have
anxiety symptoms. This disorder may resolve when the
stressor is over but also may become chronic and debilitat-
ing, requiring medication along with psychotherapy.7,38,72
The problem with the definition of an identifiable stres-
sor in cancer patients is that in most patients, even when
cured or in remission, the cancer remains a long-term stres-
sor. Clinicians should closely monitor for the recurrence of
anxiety symptoms in patients with cancer and also in cancer
survivors.
Generalized anxiety disorder. According to the DSM-IV-TR,
generalized anxiety disorder is defined as excessive anxi-
ety and worry, occurring more days than not for at least six
months, about a number of events or activities.38 The six-
month duration of symptoms in the cancer setting may not
be a reasonable criterion for a diagnosis of generalized anx-
iety disorder to be made; in this patient population, symp-
toms consistent with a diagnosis of generalized anxiety dis-
order may develop in a comparatively short time and may
have to be treated symptomatically rather than waiting for
six months to establish a diagnosis of generalized anxiety
disorder. Although a careful assessment of past psychiatric
history is necessary to identify patients who suffered from
generalized anxiety symptoms, on and off, for many years,
 Harv Rev Psychiatry
Volume 17, Number 6
clinicians may also encounter cancer patients with debilitat-
ing anxiety symptoms that developed only after a diagnosis
of cancer. The cardinal features of excessive anxiety and
worry that is difficult to control can be colored by the cancer
setting; patients may worry about the prognosis or about the
diagnostic uncertainty. They may manifest a fear of recur-
rence, with excessive worry about elevated cancer markers.
Patients may also worry about their treatment, role changes,
loss of income, and dependency on family members.73
Panic attacks and panic disorder. Panic attacks in cancer pa-
tients may reflect an exacerbation of a preexisting panic
disorder. Like depression, panic disorder is associated with
an increased risk of suicide in ambulatory cancer patients.74
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It is most important to rule out underlying medical causes
(e.g., pulmonary emboli, pancreatic cancer) or medications
(e.g., glucocorticosteroids) that may present with panic
attack–like symptoms, particularly in hospitalized cancer
patients.7
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Acute stress disorder and posttraumatic stress disorder. Acute
stress disorder involves exposure to a traumatic event; the
symptoms include the combination of one or more dissocia-
tive and anxiety symptoms, with avoidance of reminders of
the traumatic event.38 Acute stress disorder may be consid-
ered for symptoms that develop within one month of a trau-
matic event; posttraumatic stress disorder (PTSD) should
be considered for symptoms that have persisted for more
than one month after such an event.38 The prevalence of
acute stress disorder has not been established in cancer
patients. PTSD has been reported in up to 32% of cancer
patients, and studies have also shown that up to 80% of
cancer patients are likely to experience some of the symp-
toms of PTSD.2,7,75–77 Having cancer can be perceived as a
life-threatening event, and for those patients who have expe-
rienced significant psychological trauma (e.g., with a history
of physical or sexual abuse), the fear can result in dissocia-
tive experiences, avoidance of everything related to cancer,
nightmares, irritability, hypervigilance, and poor concentra-
tion. Cancer patients who go through prolonged, arduous
treatment (e.g., bone marrow transplant patients) or who
experience delirium during the course of cancer or its treat-
ment may be more likely to develop PTSD symptoms. It is
difficult, however, to assess cancer patients in terms of clas-
sic PTSD symptoms. The experience of intrusive symptoms
is of uncertain application since cancer patients often re-
port fears related to the future—but rarely flashbacks or
intrusive memories.7 Avoidance behavior is also difficult to
determine, as patients are inescapably confronted with po-
tential trauma-related stressors, including the disease and
its treatment.7
Psycho-Oncology 367
Specific phobia. Phobias of blood, needles, hospitals, mag-
netic resonance imaging machines, and radiation simula-
tors may complicate treatment adherence in cancer pa-
tients. Many patients undergoing chemotherapy experience
nausea and vomiting, and prior to the use of adequate
antiemetic regimens, about 25% to 75% of patients devel-
oped anticipatory nausea and vomiting.7 With the advent of
highly specific, centrally acting antiemetic agents, such as
the serotonin type 3 (5HT3) receptor blockers, ondansetron
and granisetron, the rate of patients with anticipatory nau-
sea and vomiting has substantially decreased. Preexisting
anxiety traits, younger age, susceptibility to motion sick-
ness, emetic chemotherapy regimens, and abnormal taste
sensations during infusions have been found to increase the
risk of developing anticipatory nausea and vomiting among
cancer patients.78
Anxiety disorder due to a general medical condition. Anxiety
symptoms that are a direct physiological consequence of
a general medical condition—as determined by history,
physical, and laboratory findings—are described as anxiety
disorders due to a general medical condition.38 Anxiety
in cancer can be caused by various conditions, includ-
ing pulmonary embolism, pulmonary edema, hypoxia,
hypoglycemia, hypercalcemia, hyperthyroidism, hypona-
tremia, complex partial seizures, sepsis, anemia, and
cardiac disorders.7,79 Hormone-secreting neoplasms
(pheochromocytoma, thyroid, and parathyroid tumors) and
paraneoplastic syndromes can also cause anxiety.7,79
Unrelieved pain is a common cause of anxiety in cancer
patients.79 In a study among hospitalized cancer patients,
the prevalence of pain was 96% among patients with anxiety,
as opposed to reports of pain by 80% of patients without
anxiety.80 Anxiety assessment can be completed only after
adequate pain relief is established.
Treatment of anxiety disorders in cancer patients. The main
goals for treating anxiety disorders in cancer patients in-
clude reducing both the patient’s overall level of distress
and specific target symptoms that may impair social or oc-
cupational functioning. The particular treatment to be used
depends on the etiology and the timing of the onset of symp-
toms. Since delirium can present with anxiety, it should
be ruled out first.7 Nonpharmacologic treatment involves
several approaches, including psychoeducation, supportive
psychotherapy, CBT, and interpersonal psychotherapy. Sev-
eral behavioral methods have been used, such as progressive
muscle relaxation, breathing exercises, meditation, biofeed-
back, systematic desensitization, distraction, and guided
imagery, all with good results in cancer patients with anxi-
ety disorders.7,81
Medications used to treat anxiety in cancer patients
include antidepressants and benzodiazepines, at lower

368 Breitbart and Alici
starting and maintenance doses compared to those used in
primary anxiety disorders. Low-dose atypical antipsychotics
can be used in treating patients who cannot tolerate benzo-
diazepines or in patients with delirium presenting with anx-
iety symptoms; by the same token, benzodiazepines should
be avoided.7,81,82
Depressive Disorders
Depression is a common psychiatric complication of cancer
and a risk factor for suicide. Cancer patients are vulnera-
ble to depressive symptoms at all stages of the illness. It is
important for clinicians to identify the point when normal
sadness or distress associated with the cancer becomes a
Harv Rev Psychiatry Downloaded from informahealthcare.com by HINARI
clinically significant depressive disorder.7 Improved recog-
nition and treatment of depressive disorders increase ad-
herence to cancer treatment, improve quality of life, and
reduce serious outcomes, including suicide and the desire
for hastened death and suicide.7
The prevalence of clinically significant depressions in
cancer patients ranges between a low of 1% and a high of
For personal use only.
50%, with the percentages varying, in part, because of the
different diagnostic measures and cutoff criteria.28 The site
of cancer, physical symptoms, and stage of cancer are addi-
tional factors that contribute to different prevalences. In a
study of terminally ill cancer patients, a symptom threshold
consistent with DSM-IV-TR criteria was associated with a
depression diagnosis in 13% of patients. A relatively minor
reduction in the symptom severity threshold elevated the
depression diagnosis to 26.1% of patients. Although depres-
sion is more prevalent among women than men in the gen-
eral population, the gender difference is not evident among
cancer patients.28,29,83 Common risk factors for depressive
disorders among cancer patients include advanced disease,
physical disability, comorbid medical illnesses, a previous
history of depression, family history of depression, uncon-
trolled pain, low social support, and recent experience of a
significant loss.7,83–85
Diagnosis of major depressive disorder (MDD) is chal-
lenging in cancer patients due to the neurovegetative symp-
toms that mimic many symptoms caused by cancer or its
treatment, such as loss of appetite, fatigue, sleep distur-
bances, psychomotor retardation, apathy, and poor concen-
tration. The assessment of depressive symptoms in cancer
patients should focus on the presence of dysphoria, anhedo-
nia, hopelessness, worthlessness, excessive or inappropriate
guilt, and suicidal ideation. In depressed cancer patients,
presence of delusions and hallucinations should prompt clin-
icians to rule out a diagnosis of delirium.7
In addition to MDD, several other subcategories of DSM-
IV-TR depressive disorders are found among cancer pa-
tients. Self-report depression scales are useful for screening
Harv Rev Psychiatry
November/December 2009
purposes but not for discriminating between a major de-
pressive disorder and a mood disorder due to general medi-
cal condition with depressive features.83 A diagnosis of ma-
jor depressive disorder or of mood disorder due to gen-
eral medical condition with depressive features is made
when depressive symptoms develop secondary to organ
failure or nutritional, endocrine, or neurological compli-
cations of cancer.7,83 A diagnosis of mood disorder due to
cancer with depressive features is appropriate when the
depressive disorder is due to an underlying cancer, such
as pancreatic cancer. A higher prevalence of depressive
disorders has been found among patients with head and
neck, breast, lung, and pancreatic cancer.84 When a med-
ication (such as interferon or glucocorticosteroids) is the
underlying cause of a depressive disorder, the diagnosis of
substance-induced mood disorder with depressive features
is used.7 Chemotherapy regimens—including vinblastine,
vincristine, interferon, procarbazine, asparaginase, tamox-
ifen, cyproterone, and corticosteroids—have been associated
with the development of depressive symptoms.83,86
The management of depressive disorders in cancer pa-
tients requires a comprehensive approach that includes
evaluation, treatment, and follow-up.83 The American Psy-
chiatry Association practice guidelines for treating depres-
sive disorders in physically healthy individuals have been
applied by the National Comprehensive Cancer Network
to the treatment of depression in cancer patients.5,87 There
are several pharmacologic and psychotherapeutic strategies
available (see Table 2). Prior to selecting an appropriate
treatment, clinicians need to take into consideration the site
of cancer, current cancer treatment, comorbid medical con-
ditions, and medications—any of which may contribute to
depressive symptoms—as well as the potential to tolerate
the antidepressant medication itself. If the depressive dis-
order is believed to be caused by a medical condition or by
a drug, the clinician should treat the underlying condition
or change the drug, though note that antidepressants are
usually started immediately in order to relieve the patient’s
suffering as quickly as possible.
Several different psychotherapeutic techniques have
been successfully employed with depressed cancer
patients.14 Psychotherapy is often combined with a phar-
macologic intervention. The most commonly utilized forms
of psychotherapy are supportive psychotherapy and CBT.
Supportive-expressive and cognitive-existential group psy-
chotherapies have also been studied and used successfully
in depressed cancer patients.14
The use of antidepressant medications in cancer patients
creates unique challenges. At the threshold, although rapid
onset of action is preferable, especially in the terminally ill,
antidepressants may take several weeks to have a therapeu-
tic effect.3 An appropriate antidepressant should be selected
based on the potential side effects of each antidepressant,
 Harv Rev Psychiatry
Volume 17, Number 6 Psycho-Oncology 369

Table 2. Psychotropic Medications Used in Treating Depression and Fatigue in Cancer Patients

Medication Starting dose Dose range Comments

Antidepressants
Selective serotonin reuptake Well tolerated; citalopram, escitalopram,
inhibitors and sertraline have the fewest drug-drug
interactions; only paroxetine and
sertraline have been tested in
randomized, controlled trials for the
treatment of cancer-related fatigue, with
evidence supporting their use in patients
with comorbid depression
Citaloprama 10–20 mg/day 10–60 mg/day
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Escitaloprama 5–10 mg/day 5–20 mg/day

Fluoxetinea 10–20 mg/day 10–60 mg/day
Paroxetinea 10–20 mg/day 10–40 mg/day
Sertralinea 25–50 mg/day 25–200 mg/day
Serotonin-norepinephrine Well tolerated; monitor blood pressure
reuptake inhibitors regularly; none of these medications has
been studied in the treatment of
cancer-related fatigue; may have possible
For personal use only.

stimulating effects

Desvenlafaxine 50 mg/day 50 mg/day

Duloxetine 20–30 mg/day 20–120 mg/day
Venlafaxine 37.5–75 mg/day 37.5–225 mg/day
Norpinephrine-dopamine
reuptake inhibitor
Bupropion 75 mg/day 75–450 mg/day Doses higher than 300 mg/day should be
administered twice daily to minimize the
risk of seizures; open-label trials suggest
its use in the treatment of cancer-related
fatigue
α-2 antagonist// 5HT2/5HT3
antagonist
Mirtazapine 7.5–15 mg/day 7.5–45 mg/day Most helpful in patients with insomnia and
anorexia; available in orally dissolvable
formulation for patients with difficulty
swallowing
Psychostimulants and Most helpful in palliative care settings due
wakefulness-promoting to rapid onset of action; randomized,
agents controlled trials for treating
cancer-related fatigue have shown a large
placebo effect and an overall favorable
side-effect profile.
Dextroamphetaminea 2.5–5 mg daily or twice daily 5–30 mg/day, usually Longer-acting formulations are available;
in two doses capsule forms can be sprinkled on food
Methylphenidatea 2.5–5 mg daily or twice daily 5–30 mg/day, usually Longer-acting forms are available; capsule
in two doses forms can be sprinkled on food
Modafinil 50–100 mg daily 50–400 mg daily, often Favorable side-effect profile
in two doses
a
Available in liquid formulations.

370 Breitbart and Alici
drug-drug interactions, patients’ prognoses, primary symp-
toms of depression, and comorbid conditions. Antidepres-
sants should be started at low doses and titrated up slowly
in medically frail cancer patients, especially in the elderly.83
Selective serotonin reuptake inhibitors (SSRIs) have become
the first line of treatment for depressive disorders in med-
ically ill cancer patients.83 They are efficacious, generally
well tolerated, and not as toxic in overdose as tricyclic an-
tidepressants. Some SSRIs, such as fluoxetine, paroxetine,
and fluvoxamine, are inhibitors of cytochrome P450 isoen-
zymes. It is therefore important to monitor for the possi-
bility of drug-drug interactions.88,89 Sertraline, citalopram,
and escitalopram have a lower risk of drug-drug interac-
tions. SSRIs with cytochrome P450 2D6 inhibitor effects
(i.e., fluoxetine and paroxetine) should be avoided in breast
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cancer patients receiving tamoxifen since cytochrome P450
2D6 enzyme plays an essential role in converting tamoxifen
to its active metabolite, endoxifen.89 Many of the SSRIs are
available in liquid form, making administration easier for
patients who cannot swallow pills.
Bupropion acts primarily on the dopamine system and
may have a mild stimulant-like effect, which can be bene-
For personal use only.
ficial for cancer patients with fatigue or psychomotor retar-
dation. It is generally tolerated well in the medically ill.83
Bupropion is associated with an increased risk of seizures
at higher doses and should be used with extreme cau-
tion in individuals with central nervous system tumors or
seizure disorders.89 Venlafaxine and duloxetine, also known
as serotonin-norepinephrine reuptake inhibitors, are gener-
ally well tolerated, with benign side-effect profiles similar
to SSRIs. Because of their effects as adjunct pain medica-
tions, venlafaxine and duloxetine are preferably used for
patients having comorbid depression and neuropathic pain,
with careful monitoring for hypertension. Mirtazapine acts
by blocking the 5HT2, 5HT3, and α2 adrenergic receptor
sites, and has antiemetic properties. Its side effects, includ-
ing sedation and weight gain, may be beneficial for many
cancer patients with insomnia and weight loss.89 The dis-
solvable tablet form is useful for patients who cannot swal-
low or who have difficulty with nausea and vomiting.
Tricyclic antidepressants have been around for many
years and are less expensive than many of the newer antide-
pressants. Because of their anticholinergic, antiadrenergic,
and antihistaminergic side effects, they are less frequently
used in cancer patients. Their role as adjunct pain medica-
tions, especially for neuropathic pain, has become their most
common indication for use in cancer patients.83 Because
of the risk of fatal hypertensive crisis when concurrently
used with tyramine rich food or sympathomimetic drugs,
monoamine oxidase inhibitors are rarely used in treating
cancer patients with depression.
Psychostimulants and wakefulness-promoting agents
may be helpful in treating depressed cancer patients’ symp-
Harv Rev Psychiatry
November/December 2009
toms of fatigue, psychomotor retardation, and poor concen-
tration. Psychostimulants have major advantages over an-
tidepressants; among other things, they have rapid onset of
action, help to relieve fatigue and opioid-related sedation,
and potentiate the analgesic effects of opiates.7 Although
side effects include anorexia, anxiety, insomnia, euphoria,
irritability, and mood lability, these effects are not common
at low doses and can be avoided by slow titration. Hyperten-
sion and cardiac complications are rare.
Electroconvulsive therapy should be considered in pa-
tients who are refractory to psychopharmacologic treat-
ment, have severe weight loss secondary to depression, ex-
hibit acute psychosis, or have a high suicide risk. Although
there are no absolute contraindications to ECT, it is used
with caution among individuals with central nervous sys-
tem tumors or cardiac problems.83
Suicide
The incidence of suicide is higher in cancer patients than
in the general population; the relative risk is twice that
of the general population.90,91 Suicide is more likely to oc-
cur in advanced cancer patients with severe depression
and hopelessness, and in the presence of poorly controlled
symptoms, particularly pain.90–94 Clinicians should espe-
cially careful to evaluate for hopelessness and for depres-
sion in terminally ill patients along with either a persistent
desire for death or suicidal intention.90 It is important to
note that these patients may have a treatable major de-
pressive episode precipitating their suicidal ideation. Prior
history of psychiatric illness, previous history of depression
or suicide attempts, recent bereavement, history of alco-
hol or other substance abuse or dependence, male gender,
family history of depression or suicide, lack of social sup-
port, and being unemployed are common risk factors for
suicide in this patient population.90–94 Untreated delirium
may lead to unpredictable suicide attempts due to impaired
judgment and impulse control.90 Older patients, individu-
als with head and neck, lung, breast, urogenital, or gas-
trointestinal cancers or with myeloma appear to have an
increased risk of suicide.91,94 An international, population-
based study from Denmark, Finland, Norway, Sweden, and
the United States has shown a small, but statistically sig-
nificant, increased risk of suicide 25 or more years after a
breast cancer diagnosis.95
It is important to recognize and aggressively treat de-
pressed patients at high risk of suicide and to address
suicidal risk with psychiatric hospitalization if necessary.
Maintaining a supportive relationship, controlling symp-
toms (e.g., pain, nausea, depression), and involving the fam-
ily or friends are the initial steps in managing suicidal pa-
tients. Medical staff and family may need to be reminded
 Harv Rev Psychiatry
Volume 17, Number 6
of the competent patient’s right to refuse all treatments,
even life-saving ones. A careful evaluation of the suicidal
patient includes an exploration of the reasons for suicidal
thoughts and the seriousness of the risk, taking into ac-
count the disease stage and prognosis. The clinician should
listen empathically, without appearing critical or judgmen-
tal. Allowing the patient to discuss suicidal thoughts often
decreases the risk of suicide—despite the common belief to
the contrary. Patients often reconsider and reject the idea of
suicide when the physician acknowledges the legitimacy of
that option and the patient’s need to retain a sense of control
over the dying process.90
Cancer-Related Fatigue
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Cancer-related fatigue is a persistent, subjective sense of
physical, emotional, and cognitive tiredness or exhaustion
related to cancer or cancer treatment that is usually re-
fractory to sleep and rest, interferes with usual function-
ing, and is associated with reduced quality of life as well
as considerable psychological and functional morbidity.96,97
For personal use only.
Fatigue in cancer patients has been significantly associated
with depression, hopelessness, desire for hastened death,
and overall psychological distress.97,98 Patients with cancer
perceive fatigue as the most distressing symptom associated
with cancer and its treatment—more distressing than pain,
nausea, and vomiting.99
The reported prevalence of cancer-related fatigue ranges
from 4% to 100%, depending on the specific cancer popu-
lation studied and the methods of assessment.98 Fatigue is
present at the time of diagnosis in about 50% of cancer pa-
tients. Approximately 60% to 96% of patients undergoing
treatment for cancer report fatigue. Fatigue is also preva-
lent in long-term cancer survivors.99,100
The etiologies of cancer-related fatigue are complex and
varied, including tumor by-products, cytokines (IL-1, IL-6,
TNF-α), opioids or other drugs (such as antidepressants,
benzodiazepines, beta-blockers), hypogonadism, hypothy-
roidism, cachexia, malnutrition, anemia, chemotherapy, ra-
diation therapy, bone marrow transplantation, and treat-
ment with biological response modifiers.96,97,101 In addition,
pain, sleep deprivation, emotional distress, and reduced
physical activity in cancer patients have been related to
fatigue.
Fatigue is difficult to quantify. There are various stan-
dardized, self-report scales, most of which have been devel-
oped in the context of cancer.96,97 Given the multifactorial
nature of fatigue, accessory scales (e.g., depression scales)
and measurements of certain biological parameters should
be used—in addition to fatigue-assessment tools—in order
to obtain the most comprehensive evaluation of a patient’s
fatigue.
Psycho-Oncology 371
ICD-10 Criteria for Cancer-Related Fatigue
A. Six (or more) of the following symptoms have been
present every day or nearly every day during the
same 2-week period in the past month, and at least
one of the symptoms is (A1) significant fatigue:
A1. Significant fatigue, diminished energy, or in-
creased need to rest, disproportionate to any
recent change in activity level
A2. Complaints of generalized weakness or limb
heaviness
A3. Diminished concentration or attention
A4. Decreased motivation or interest to engage
in usual activities
A5. Insomnia or hypersomnia
A6. Experience of sleep as unrefreshing or non-
restorative
A7. Perceived need to struggle to overcome
inactivity
A8. Marked emotional reactivity (e.g., sadness,
frustration, or irritability) to feeling fatigued
A9. Difficulty completing daily tasks attributed
to feeling fatigued
A10. Perceived problems with short-term memory
A11. Postexertional malaise lasting several hours
B. The symptoms cause clinically significant distress
or impairment in social, occupational, or other im-
portant areas of functioning.
C. There is evidence from the history, physical exam-
ination, or laboratory findings that the symptoms
are a consequence of cancer or cancer therapy.
D. The symptoms are not primarily a consequence of
co-morbid psychiatric disorders, such as major de-
pression, somatization disorder, somatoform disor-
der, or delirium.
Source: Adapted from Cella et al. (1998).102
Recognizing the need for a standardized definition of fa-
tigue, a group of expert clinicians proposed a set of diagnos-
tic criteria for cancer-related fatigue, which are included in
the tenth edition of the International Classification of Dis-
eases (see text box).102 A standardized interview guide has
been designed and validated for use in identifying patients
with cancer-related fatigue.103
Fatigue and depression may coexist in cancer patients,
and there is considerable overlap of symptoms of these
two conditions, including decreased energy and motiva-
tion, sleep disturbances, diminished concentration, atten-
tion, and memory. A diagnosis of depression is becomes more
likely in the presence of hopelessness, feelings of worth-
lessness or guilt, suicidal ideation, and a family history of

372 Breitbart and Alici
depression. The nature of any causal relationship between
cancer-related fatigue and depression is unclear.96,97
All cancer patients should be screened for fatigue at their
initial visits and at regular intervals during and follow-
ing cancer treatment. The National Comprehensive Can-
cer Network practice guidelines on cancer-related fatigue
recommend the use of numerical self-report scales or ver-
bal scales to assess the severity of fatigue.97 The follow-
ing are recommended for patients with moderate to severe
levels of fatigue: a focused history and clinical examina-
tion; evaluation of the pattern of fatigue, associated symp-
toms, and interference with normal functioning; assessment
and treatment of the potentially reversible causes of fatigue
(such as pain, emotional distress, sleep disturbance, anemia,
hypothyroidism); and elimination of nonessential centrally
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acting drugs.97
The National Comprehensive Cancer Network has also
issued guidelines for the nonpharmacological treatment of
cancer-related fatigue.97,104,105 Activity enhancement and
psychosocial interventions (e.g., education, support groups,
individual counseling, stress-management training) have
been well-supported by research.104,105 Dietary manage-
For personal use only.
ment, attention-restoring therapy, and sleep therapy have
also been recommended.104,105
Psychostimulants (e.g., methylphenidate, dextroam-
phetamine), wakefulness promoting agents (e.g., modafinil),
and antidepressants have been studied for use in treat-
ing cancer-related fatigue.105–112 Psychostimulants are well
tolerated and, despite a large placebo effect, appear to
help improve fatigue. Antidepressants are most effective
in patients with underlying depression.110–112 Activating
antidepressants such as bupropion may be more effective
than others in treating fatigue symptoms. It is important
to emphasize that more research is needed to evaluate
the efficacy of pharmacologic interventions, as current ev-
idence falls short of providing sufficient evidence to rec-
ommend specific medications for treating cancer-related
fatigue.
“Chemobrain”: Cognitive Changes Associated with
Chemotherapy
The term chemobrain has been used to describe cog-
nitive changes experienced by cancer patients following
chemotherapy. Growing research evidence supports the
complexity of “chemobrain” phenomena.113,114 Multiple po-
tential confounders other than chemotherapy have been im-
plicated in the development of cognitive impairment in can-
cer patients, including hormonal therapy, surgery, anxiety,
depression, fatigue, medications (such as opioids), genetic
predisposition, comorbid medical conditions, and parane-
oplastic syndromes.104 Hurria and colleagues113 have pro-
posed replacing the term chemobrain by “cancer- or cancer
Harv Rev Psychiatry
November/December 2009
therapy–associated cognitive changes” in order to reflect the
complexity of the problem.
The specific mechanisms by which chemotherapeutic
agents may cause cognitive impairment remain largely
unknown. Possible mechanisms include direct neurotoxic
effects, oxidative damage, immune dysregulation with
the release of cytokines, vascular injury, and hormonal
changes.113,114 Genetic predisposition (such as presence of ε4
allele of the apolipoprotein E gene that regulates neuronal
repair or plasticity) has been replicated as a risk factor for
chemotherapy-induced cognitive changes.115 Several studies
have found cognitive impairment to be associated with the
number of cycles and higher doses of chemotherapy.113,114
Current research indicates that the cognitive domains
most commonly affected by chemotherapeutic agents are vi-
sual and verbal memory, attention, executive functioning,
and information-processing speed.114 Studies to date have
been limited, however, by the use of different assessment
tools, inclusion of heterogeneous patient populations, small
sample sizes, and differences in definition of cognitive im-
pairment. Elderly patients with cancer—the age group at
highest risk of developing cognitive impairment from any
cause—have largely been excluded from studies.113
Several pharmacologic treatment approaches have been
considered and studied in treating chemobrain, includ-
ing methylphenidate, erythropoietin, gingko biloba, and
cholinesterase inhibitors—all with inconclusive results.114
FAMILY ISSUES AND BEREAVEMENT
Families and other caregivers of cancer patients are often
overburdened by their responsibilities—a problem that is of-
ten ignored. Primary caregivers have been noted to worsen
over time, even in the face of the patient’s stabilization or
improvement. Studies of families after bereavement or can-
cer survival show a significant incidence of impaired func-
tioning, with a downward trend, over extended periods of
time.116,117 In medical settings, high-risk families can be
identified early and significantly helped by mental health
professionals. A small number of families require formal
family therapy, which must be done with a realistic under-
standing of the medical facts and the medical milieu. Most
families manage with short-term crisis interventions and a
therapeutic commitment to the family as a whole, not just
to selected members.7 In family-focused grief therapy, the
patient and family meet together, to process the events and
anticipate the upcoming loss.118 Therapy continues for a few
sessions after the patient’s death, helping the family to con-
solidate the positive achievements made while the patient
was still alive. Children in the family also require attention;
it is important to provide guidance to the adult caregivers
about answering children’s questions.
 Harv Rev Psychiatry
Volume 17, Number 6
PSYCHOLOGICAL ISSUES FOR STAFF
The stress on health care providers has been documented
in studies across many settings. Communication problems
between doctors, nurses, and patients lead not only to pa-
tient dissatisfaction, but also to lower job satisfaction and
self-esteem for physicians.2,7 Staff undergo a developmen-
tal process when they begin to work intensively with cancer
patients. A high initial level of dysphoria, anxiety, sadness,
and numbing recedes over the first few months, displaced
by the need to demonstrate competence and the ability to
survive. Over the next few months, existential issues are al-
lowed to surface, and staff members shape a deeper adapta-
tion that engages their whole personality.2 Informal support
and peer group interactions are important for a successful
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resolution, as are open communications and good orienta-
tion procedures. A team approach encourages the sharing of
difficult tasks, prevents a sense of being indispensable, and
encourages staff cohesion.15
CONCLUSION
For personal use only.
In order to provide optimal, holistic care to cancer patients,
it is essential to integrate a mental health professional—one
familiar with the psychological aspects of cancer—into the
cancer care team. Important elements of psycho-oncologic
care range from screening strategies, to identifying patients
and families at risk, to recognizing and treating common
psychiatric disorders complicating the course of cancer ill-
ness and treatment. While great advances have been made
in the fields of psycho-oncology in general, further research
is needed to improve assessment and treatment of psychi-
atric syndromes in cancer patients, to understand the na-
ture of distress in all stages of disease and survival, to as-
sess the needs of special subgroups such as geriatric cancer
patients, to understand the mechanisms and implications
of cognitive changes associated with cancer treatment, to
advance our ability to integrate basic science insights into
clinical practice, and, finally, to continue the development
and study on intervention modalities for the full range of
psychological and psychiatric symptoms and syndromes en-
countered in the oncology setting.
Declaration of interest: The authors report no conflicts
of interest. The authors alone are responsible for the content
and writing of the article.
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