Independent learning program for GPs

Unit 468 March 2011

Bipolar
disorders

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www.racgp.org.au/check
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disorder: Maintenance treatment of bipolar I disorder, as monotherapy or in combination with lithium or
sodium valproate, for the prevention of relapse/recurrence of manic, depressive or mixed episodes
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of SEROQUEL immediate release may be switched to SEROQUEL XR at
equivalent total daily dose taken once daily. Elderly: Use caution. Slower
rate of titration recommended. CONTRAINDICATIONS: Hypersensitivity
to any component of SEROQUEL XR. PRECAUTIONS: Concomitant
PBS Information: Authority required (STREAMLINED). Maintenance treatment of bipolar I disorder. Monotherapy,
for up to 6 months, of an episode of acute mania associated with bipolar I disorder. Treatment of schizophrenia. This
product is not listed on the PBS for bipolar depression, major depressive disorder or generalised anxiety disorder.
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 Independent learning program for GPs

Medical Editors
Kath O’Connor

Bipolar disorders
Catherine Dodgshun
Editor
Nicole Kouros
Unit 468 March 2011
Production Coordinator
Morgan Liotta
From the editor 2 Senior Graphic Designer
Jason Farrugia
Case 1 Adam presents with depression 3
Graphic Designer
Case 2 Sue complains of depression and irritability 8 Beverly Jongue
Case 3 Sally hasn’t been her usual self 13 Authors
Andrew Gleason
Case 4 Sam lost his job 18 David Castle
Leon Piterman
Case 5 Is Mrs Smith depressed? 21 Kay Jones
References 24 Reviewer
Andrew Baird
Resources 25
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FROM THE EDITOR check Bipolar disorders

This unit of check focuses on bipolar disorders with clinical scenarios relating to diagnosis of depressive, hypomanic
and manic episodes; diagnosis of the bipolar disorders; assessment of risk to the patient and others; identification
of predisposing and precipitating factors, and pharmacological and nonpharmacological management of the bipolar
disorders. The authors of this unit bring a wealth of clinical, research and teaching experience to the topic.
The authors are:
t
Andrew Gleason BSc, MBBS(Hons), Senior Registrar, Primary Mental Health Team, St Vincent’s Hospital,
Victoria. His clinical interests include neuropsychiatry, old age psychiatry, and consultation-liaison psychiatry
t
David Castle MBChB, MSc, MD, MRCPsych, FRANZCP, Chair of Psychiatry, St Vincent’s Hospital and the
University of Melbourne, Victoria. His research and clinical interests include longitudinal care for people with
psychotic disorders, bipolar disorders, substance abuse, and medical problems associated with psychotic
disorders
t
Leon Piterman AM, MBBS, MD, MMed, MEdSt, MRCP, FRCP, FRACGP, Head, School of Primary Care, Monash
University, Victoria. His clinical and research interests lie in the areas of cardiovascular disease, mental health
and medical education
t
Kay Jones BSW, MTD, PhD, Senior Research Fellow, Department of General Practice, Monash University,
Victoria. Her research areas include chronic disease management (osteoarthritis, obesity, mental health), and
knowledge translation including uptake of guidelines and information technology. Current research and education
development include online activities about osteoarthritis, depression and bipolar disorder.
The learning objectives of this unit are to:
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display increased confidence in the diagnosis of hypomania, mania and the bipolar disorders and recognise the
differing clinical contexts in which the bipolar disorders may present
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display an increased awareness of the possibility of a bipolar disorder in patients presenting with depression
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display increased confidence in the assessment of risk in the bipolar disorders
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understand the role of pharmacological and nonpharmacological strategies used in the bipolar disorders
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understand the role of the GP in the care of patients with bipolar disorder in regard to monitoring, collaborative
continuing care and management of physical and psychological comorbidities and social repercussions
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display increased confidence in monitoring the use of lithium and detecting lithium toxicity
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appropriately assess when to refer a person with suspected or diagnosed bipolar disorder to a psychiatrist.
This issue marks the conclusion of my role as medical editor of the check program. I am commencing a new
role as a medical editor with Australian Family Physician, alongside senior medical editor, Dr Carolyn O’Shea and
medical editor, Dr Rachel Lee. I would like to extend a warm welcome to the incoming check medical editor, Dr
Catherine Dodgshun.
Working on check has been an extremely rewarding experience. I am grateful to all the authors and reviewers I
have worked with for the generous gift of their time and expertise and to the wonderful admin, editing, graphic
design and IT staff for all their hard work.
We hope this unit will help you to more confidently assess and manage patients who present with bipolar disorders
in the general practice setting.

Best wishes

Kath O’Connor
Medical Editor

2
check Bipolar disorders
CASE 1
ADAM PRESENTS WITH DEPRESSION
Adam, aged 26, is an internet technology
consultant. He presents with a 3 month history of
progressive lowering of mood which is worse in
the morning. He experiences no pleasure in any
activities. He has trouble falling asleep, wakes
3 hours before his alarm, and is unable to get back
to sleep. He has no appetite and has lost 5 kg. He
reports trouble functioning at work and feels guilty
about this. There is no clear precipitant.
QUESTION 1
What is your differential diagnosis for Adam’s presentation?
QUESTION 2
What are some of the risks associated with Adam’s symptoms?
QUESTION 3
How would you assess Adam’s risk of suicide?
CASE 1
FURTHER HISTORY
Adam lives with his girlfriend and has no past medical or
psychiatric history. He smokes marijuana once every few
months and binge drinks up to 15 standard drinks about once
per month. His grandfather died of suicide at age 42 but the
family never talks about this.
Physical examination, full blood count, urea, electrolytes,
creatinine, liver function and thyroid function tests are all
normal. Adam is commenced on venlafaxine 75 mg per day.
This is well tolerated and increased to 150 mg per day
2 weeks later.
Three weeks after this, Adam’s girlfriend, Caity, comes
to see you without Adam. She is teary and distressed.
She says that Adam ‘is not his usual self’. He has become
uncharacteristically irritable, is easily distracted, and is talking
much more than usual. He is sleeping only a few hours each
night but has a lot of energy. Caity thinks he might have slept
with another woman, as he didn’t come home one night.
Adam told her that he is going to be the next Bill Gates and is
planning on using all his savings to set up his own company.
He doesn’t think anything is wrong and refuses to seek
medical attention.
QUESTION 4
What is the differential diagnosis now?
QUESTION 5
What are the risks associated with a manic episode?
3
CASE 1
QUESTION 6
What advice will you give to Caity? How will you manage this
situation?
FURTHER HISTORY
Adam was taken to hospital under the Mental Health Act
after being assessed by the on call psychiatry team. He spent
3 weeks as an inpatient and was discharged on sodium
valproate 500 mg twice per day and olanzapine 10 mg at
night. The discharge diagnosis was ‘manic episode due to
antidepressant’. Adam now has a case manager who he sees
weekly and his medications are managed by a psychiatry
registrar. Adam has received some education but no specific
psychological interventions. Although he doesn’t think
anything was ever wrong, he has been taking his medication.
QUESTION 7
Does Adam have bipolar disorder?
QUESTION 8
What is the typical first presentation of bipolar disorder?
4
check Bipolar disorders
QUESTION 9
What features of depression might suggest a risk of bipolar disorder?
QUESTION 10
Describe your initial and ongoing management of Adam.
CASE 1 ANSWERS
ANSWER 1
The differential diagnosis in Adam’s case includes both psychiatric
and organic/medical conditions. Possibilities that could give rise to
this symptom complex are psychiatric conditions such as a mood
disorder (eg. major depressive disorder, bipolar disorder, dysthymic
disorder), anxiety disorder, personality disorder, eating disorder,
drug and/or alcohol abuse or withdrawal. In addition, a wide range
of organic/medical conditions could give rise to Adam’s symptoms.
These include metabolic disorders such as thyroid disease, infection
and sleep related disorders. Table 1 outlines the wide range of
psychiatric and medical conditions that can cause depressive
symptoms.
ANSWER 2
With symptoms suggestive of depression there is a risk of the patient
harming themselves as well as a risk of the patient harming others.
Risks include:
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suicide
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drug and/or alcohol abuse
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relationship breakdown
check Bipolar disorders
Table 1. Differential diagnoses of depression1
Psychiatric conditions
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Mood disorders (eg. major depressive disorder, bipolar disorder,
dysthymic disorder)
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Adjustment disorder
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Personality disorder
t
Anxiety disorders (eg. obsessive compulsive disorder, post-traumatic
stress disorder, panic disorder, phobias)
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Eating disorders
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Drug and/or alcohol abuse or dependence
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Drug intoxication or withdrawal
Organic/medical conditions
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Metabolic and endocrine conditions (eg. thyroid and glucocorticoid
disturbances)
t
Infection, postinfective states
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Nutritional deficiency (eg. vitamin B12, folate)
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Anaemia
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Malignancy
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Neurological disease (eg. demyelinating conditions, focal CNS disease)
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Sleep related disorders, especially sleep apnoea
Normal life stressors
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Bereavement (which can be normal or pathological)
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Other psychosocial stressors
Modified and reproduced with permission from McGraw-Hill Australia
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occupational problems possibly leading to unemployment
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financial problems.
ANSWER 3
Assessing risk of suicide in depression includes the following.
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Ask questions about suicidal intent:
– Have you had thoughts of wanting to die?
– Have you had thoughts of wanting to end your life?
– How often and how persistent are these thoughts?
– How long have you had these thoughts?
– Do you have a plan (eg. method, time, and place)?
– What has stopped you acting on them?
– What hopes and plans do you have for the future?
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Assess access to means of suicide
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Obtain a collaborative history to elicit indirect statements of intent to
suicide such as giving away possessions
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Obtain history on:
– past suicidal attempts and the seriousness of these attempts
– personal and social strengths and supports
– adverse life events (eg. unemployment, death of a loved one,
separation, divorce, childhood abuse)
– family history of suicide
CASE 1
– past history of psychiatric illness
– concurrent substance abuse or addictive behaviour
– concurrent chronic medical ill health
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Keep in mind other factors such as age, gender, place of residence,
occupation, ethnicity, marital status and sexual orientation can
influence the propensity to suicide.
ANSWER 4
The differential diagnosis now includes:
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substance-induced mania or psychosis (eg. due to antidepressant use
or illicit drugs)
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bipolar disorder – either a manic episode or a mixed episode
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a psychotic disorder (eg. schizophrenia)
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mania or psychosis due to a medical condition.
Note that antidepressants often have activating side effects such as
impaired sleep and agitation but these are distinct from antidepressant-
induced mania, and usually settle within the first few weeks of treatment.
ANSWER 5
Potential risks associated with a manic episode include:2
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risk taking behaviour resulting from a belief that one is invulnerable
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excessive spending
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alcohol or substance use and the risks associated with intoxication
(people with psychiatric symptoms often ‘self medicate’ with drugs or
alcohol)
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irritability, aggression and socially disruptive behaviour
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disinhibited behaviour such as uncharacteristic sexual activity,
including the associated risks (eg. sexually transmitted infection)
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inappropriate behaviour (eg. being sarcastic, rude, aggressive) that
can damage reputation
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risks related to a potential undiagnosed medical condition (eg.
cerebral neoplasm, HIV infection).
ANSWER 6
You could ask Caity whether Adam knows she has come to see you
and if he is happy with her discussing her concerns with you. You
could also ascertain whether she thinks she can convince Adam to
come and see you for a consultation, or if she could try to encourage
him to present to a mental health service or emergency department
or to accept an assessment from the local outreach on call psychiatric
team (see Resources – on call services are available in most
metropolitan areas of Australia).
Advice to Caity could include:
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explaining what might be causing Adam’s behaviour (eg. mania,
drugs, medication) but importantly that further evaluation is needed
in order to be able to determine the cause of Adam’s symptoms and
initiate appropriate treatment
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emergency contingency management, for instance, if Caity feels that
Adam’s symptoms or behaviour are placing her or someone else at
immediate risk of harm, she should contact the police
5
CASE 1
t
explanation that while it would be ideal if Adam agreed to treatment,
according to state and territory law, there are situations in which
people can be assessed and treated when they don’t think they
need help (see Resources for links to state and territory mental
health acts).
Supporting Caity and her situation is important. Balancing
confidentiality with potential risks in such cases, especially if Adam
were to refuse assessment or referral, can be challenging. The Royal
Australian and New Zealand College of Psychiatrist’s Code of Ethics
provides some guidelines on maintaining confidentiality – these
guidelines apply to GPs as well as psychiatrists (see Resources).
ANSWER 7
Adam does not qualify for a diagnosis of bipolar disorder at this stage
under International Classification of Diseases (ICD-10)3 or Diagnostic
and Statistical Manual of Mental Disorders (DSM-IV-TR)4 (the most
commonly used diagnostic systems) because his manic episode was
induced by an antidepressant.
An episode of antidepressant-induced mania is thought to be part
of a bipolar disorder ‘spectrum’.5 Adam is at an increased risk of
spontaneous manic or hypomanic episodes compared to the general
population, and would be at risk of a recurrent manic episode or
rapid cycling if he were again prescribed an antidepressant without a
concurrent mood stabiliser.
A DSM-IV-TR diagnosis of bipolar I disorder requires at least one
manic or mixed episode. A mixed episode is characterised by a
period of time (lasting at least 1 week) in which the criteria are met
both for a manic episode and for a major depressive episode. The
criteria outlined in DSM-IV-TR relating to diagnosing a manic episode
and diagnosing a hypomanic episode are presented below.
Criteria for diagnosing a manic episode4
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A distinct period of abnormally and persistently elevated, expansive,
or irritable mood, lasting at least 1 week (or any duration if
hospitalisation is necessary)
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During the period of mood disturbance, three (or more) of the
following symptoms have persisted (four if the mood is only irritable)
and have been present to a significant degree:
– inflated self esteem or grandiosity
– decreased need for sleep (eg. feels rested after only 3 hours of
sleep)
– more talkative than usual or pressure to keep talking
– flight of ideas or subjective experience that thoughts are racing
– distractibility (ie. attention too easily drawn to unimportant or
irrelevant external stimuli)
– increase in goal-directed activity (either socially, at work or school,
or sexually) or psychomotor agitation
– excessive involvement in pleasurable activities that have a high
potential for adverse consequences (eg. engaging in unrestrained
buying sprees, sexual indiscretions, or foolish business
investments)
6
check Bipolar disorders
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The symptoms do not meet criteria for a mixed episode
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The mood disturbance is sufficiently severe to cause marked
impairment in occupational functioning or in usual social activities or
relationships with others, or to necessitate hospitalisation to prevent
harm to self or others, or there are psychotic features
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The symptoms are not due to the direct physiological effects of a
substance (eg. a drug of abuse, a medication, or other treatment) or a
general medical condition (eg. hyperthyroidism).
Note: manic-like episodes that are clearly caused by somatic
antidepressant treatment (eg. medication, electroconvulsive therapy, light
therapy) should not count toward a diagnosis of bipolar I disorder.4
Criteria for diagnosing a hypomanic episode4
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A distinct period of persistently elevated, expansive, or irritable mood,
lasting throughout at least 4 days, that is clearly different from the usual
nondepressed mood
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During the period of mood disturbance, three (or more) of the following
symptoms have persisted (four if the mood is only irritable) and have
been present to a significant degree:
– inflated self esteem or grandiosity
– decreased need for sleep (eg. feels rested after only 3 hours of sleep)
– more talkative than usual or pressure to keep talking
– flight of ideas or subjective experience that thoughts are racing
– distractibility (ie. attention too easily drawn to unimportant or
irrelevant external stimuli)
– increase in goal-directed activity (either socially, at work or school, or
sexually) or psychomotor agitation
– excessive involvement in pleasurable activities that have a high
potential for adverse consequences (eg. engaging in unrestrained
buying sprees, sexual indiscretions, or foolish business investments)
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The episode is associated with an unequivocal change in functioning
that is uncharacteristic of the person when not symptomatic
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The disturbance in mood and the change in functioning are observable
by others
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The episode is not severe enough to cause marked impairment in social
or occupational functioning, or to necessitate hospitalisation, and there
are no psychotic features
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The symptoms are not due to the direct physiological effects of a
substance (eg. a drug of abuse, a medication, or other treatment) or a
general medical condition (eg. hyperthyroidism).
Note: hypomanic-like episodes that are clearly caused by somatic
antidepressant treatment (eg. medication, electroconvulsive therapy, light
therapy) should not count toward a diagnosis of bipolar II disorder.4
Presented below are some of the questions that Blackdog website provides
that can be asked of patients to ascertain whether they may have had
symptoms of hypomania (see Resources).
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Do you have times when your mood ‘cycles’, ie. Do you experience ‘ups’
as well as ‘downs’?
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During the ‘ups’ do you feel more ‘wired’ and ‘hyper’ than you would
experience during times of normal happiness?
check Bipolar disorders
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If yes to the above question. During these ‘up’ times, do you:
– Feel more confident and capable?
– Feel very creative with lots of ideas and plans?
– Spend or wish to spend significant amounts of money?
– Work harder and are more motivated?
– Feel irritated?
– Have an increased interest in sex?
– Talk over people?
– Do fairly outrageous things?
– Sleep less and not feel tried?
– Feel angry?
ANSWER 8
The first presentation of bipolar disorder is typically with depression.
People with bipolar disorder frequently seek help from a number of
professionals over a period of years before a diagnosis is made. One
study reported that people had seen a mean of four doctors, and
over one-third had waited 10 years before an accurate diagnosis was
made.6,7
It is important for the clinician to consider when assessing every
patient with depression whether it is a depressive episode of bipolar
disorder. It is important for the clinician to be aware that the absence
of past psychiatric history does not exclude previous hypomania. It is
essential to ask specifically about symptoms that could suggest past
manic/hypomanic episodes in everyone who presents with depression
because such symptoms may not be volunteered by the patient.
Screening for mania/hypomania can be extremely challenging,
even for experienced psychiatrists. If unsure, refer the patient to a
psychiatrist or mental health service. A diagnosis of bipolar disorder
has a major impact on the patient, and mood stabilisers can have
significant side effects. Similarly, an antidepressant-induced manic
episode can have major morbidity.
ANSWER 9
The cross-sectional features of a depressive episode are not reliable
in distinguishing bipolar from unipolar depression, but some features
are more common in bipolar depression. These include recurrent
episodes, short duration of episodes, early age of onset, feelings
of worthlessness, low self esteem, social withdrawal, hypersomnia,
hyperphagia, weight gain, ‘atypical features’ (eg. leaden paralysis),
mood lability, psychotic features, psychomotor retardation, and a family
history of bipolar disorder. Signs suggestive of bipolar disorder in
depressed patients are listed below:8
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worse or ‘wired’ when taking antidepressants
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hypomania in the patient’s history
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irritable
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psychomotor retardation or agitation
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loaded family history
t
abrupt onset or termination of depressive bouts
CASE 1
t
seasonal or postpartum pattern
t
hyperphagia and hypersomnia
t
early age at depression onset
t
delusions, hallucinations or other psychotic features.
These features are a flag of possible bipolarity in:
t
depressed patients in whom past history of hypomanic or manic
episodes is ambiguous
t
depressed patients with a family history of bipolar disorder
t
young patients with recurrent depressive episodes.
These features are not perfectly sensitive, as illustrated by Adam’s case,
and it is unlikely that they have sufficient specificity to make a diagnosis
of bipolar disorder in the absence of other features, but they should
raise the vigilance of the treating clinician.6
ANSWER 10
Your initial and ongoing management of Adam includes:
t
establishing rapport and maintaining a healthy therapeutic
relationship with Adam and Caity
t
psychoeducation and support for Adam, Caity and his family
t
assessment and management of Adam’s comorbidities
t
ensuring Adam understands the risks of marijuana use
t
monitoring Adam’s drug and alcohol use
t
utilising mental health treatment plans (Medicare Item Numbers:
2710 or 2702, 2712 and 2713) to arrange consultations and
referrals9
t
developing and coordinating team based care with appropriate
mental health professionals (eg. a psychiatrist, psychologist,
community mental health team)
t
considering psychotherapeutic options: psychoeducation, cognitive
behavioural therapy (CBT), interpersonal and social rhythm therapy
and family therapy have all shown benefit as adjunctive treatments10
t
providing advice and support for Adam regarding diet, physical
exercise and sleep routine
t
discussing early warning signs with Adam and Caity,11 and involving
them in developing a crisis plan
t
monitoring moods with a mood chart is extremely useful11
t
monitoring for medication side effects, including metabolic effects:
check his weight/body mass index (BMI), waist circumference and
lipids12–14
t
performing haematological and liver function tests every 3 months
after commencing sodium valproate for the first year, then annually.12
The frequency of GP review would depend on clinical need, as well
as on how often Adam is seen by a doctor at the public mental health
service. After being discharged from hospital, he should probably have
a medical review at least weekly until his clinical situation settles.
7
CASE 2 check Bipolar disorders

QUESTION 2
CASE 2
What is your differential diagnosis?
SUE COMPLAINS OF DEPRESSION AND
IRRITABILITY
Sue is 52 years of age with a past history of
hypercholesterolaemia, hypertension and obesity
(BMI: 31 kg/m2).
She presents complaining that her partner of 10
years, Bill, has recently moved out because he has
found her too irritable to live with over the last 6
months. Before this, Sue felt ‘depressed’ for a while.
She stopped menstruating 1 year ago. Sue asks if
her mood changes might be related to menopause.

QUESTION 1
Is menopause associated with depression?
QUESTION 3
What are the symptoms and signs of mania and hypomania? What
factors distinguish mania from hypomania?

FURTHER HISTORY
About 10 months ago, Sue had a 4 month period of pervasive
low mood, associated with poor sleep and an increase in
appetite. Her symptoms resolved spontaneously, but after
a brief interlude of euthymia, a 6 month period of sustained
irritability followed.
Sue felt ‘great’ during this time, and it is only since Bill moved
out that she began to consider the veracity of his complaint
that she was irritable all day, every day. She was also sleeping
less than usual but felt energetic and fully rested. She had QUESTION 4
an increased interest in sex and spent large amounts of time
What investigations should be done?
writing several books, but didn’t complete any of them. Bill had
commented that she didn’t stop talking which contrasted to
her usual somewhat taciturn state. These symptoms resolved
a few weeks ago.
Sue describes herself as usually placid and agreeable.
In spite of this, a number of relationships in the past
have ended during times when her partner said she was
uncharacteristically irritable and restless for periods of weeks
to months. The first episode took place in her mid-20s. She
was diagnosed with depression a number of times by her GP,
but found that antidepressants always caused insomnia and
made her disinhibited. She has never seen a psychiatrist and
she doesn’t use drugs or alcohol.

8
check Bipolar disorders CASE 2

QUESTION 5 QUESTION 8
Does Sue need further assessment by a psychiatrist? When should a What is the main source of disability in bipolar disorder?
GP refer a patient with suspected or established bipolar disorder?

FURTHER HISTORY QUESTION 9

Sue is referred to a primary mental health service (a public
Sue asks for more information. What resources can you refer her to?
service that provides psychiatric assessment and management
advice to GPs, available in some parts of Australia) for
clarification of her diagnosis. The psychiatrist diagnoses her
with bipolar II disorder and recommends that Sue have a trial
of lithium and psychological treatment.

QUESTION 6
How do people with bipolar II disorder typically present?

QUESTION 10
Sue tells you that she had CBT once, but it didn’t suit her, and
may have made things worse. Given that she is currently euthymic,
should you initiate psychological treatment? If so, what treatments
would you consider?

QUESTION 7
Is bipolar II disorder less severe than bipolar I disorder?

9
CASE 2 check Bipolar disorders

QUESTION 11 QUESTION 13
What ongoing monitoring is required once serum lithium levels are Should hormone replacement therapy (HRT) be considered for Sue’s
stable? What are the symptoms and signs of toxicity? affective symptoms?

CASE 2 ANSWERS

QUESTION 12
What might happen if Sue abruptly stopped taking lithium? ANSWER 1
Many physical conditions are associated with psychiatric symptoms,
and menopause is no exception (Figure 1). There is no clear
evidence that menopause is a risk factor for the development of
psychiatric illness – the majority of women do not experience a
major depressive episode at the time of menopause, but some
women may be particularly vulnerable at this life stage. Most at risk
of depression are those who have a past history of mood problems,
as well as those who experience many or intense physical symptoms
during menopause.15
In situations where overlapping symptoms make it difficult to make
a definitive diagnosis of a major depressive episode, it is generally
thought that it is best to have a low threshold for a diagnosis
of major depression and a trial of treatment. In Sue’s case, her
menopausal symptoms may also need treatment.

Changes associated with menopause and depression

Depression Menopause
Low mood Fatigue Menstrual irregularity, amenorrhoea
Irritability Poor concentration Vasomotor disturbance
Anhedonia Insomnia (hot flushes, diaphoresis)

Suicidality Weight change (usually gain in menopause) Vaginal atrophy and dryness

Feelings of worthlessness Irritability Osteoporosis

Psychomotor agitation/retardation Libido change

Figure 1. Changes associated with menopause and depression, with overlap shown.16 Adapted and reproduced with permission from Physicians Postgraduate Press

10
check Bipolar disorders
ANSWER 2
The differential diagnosis includes:
t
bipolar II disorder, most recent episode hypomanic
t
bipolar I disorder,
– most recent episode manic
– most recent episode mixed
t
recurrent episodes of major depression with irritability
t
physical illness such as an endocrine disorder
t
adjustment disorder
t
personality disorder
t
(Sue also has a concurrent menopausal syndrome).
Note that bipolar I disorder is characterised by at least one manic
or mixed episode; bipolar II disorder is characterised by least one
major depressive episode and at least one hypomanic episode but
no manic or mixed episodes.
ANSWER 3
Mania is a syndrome characterised by a distinct period of persistently
and abnormally elevated, expansive, or irritable mood, accelerated
speech, racing thoughts with flight of ideas, increased activity and
reduced need for sleep (Table 2).6 The severity and duration of the
mood disturbance, impairment in social and occupational functioning,
and presence or absence of psychotic features distinguish a manic
from a hypomanic episode. The term hypomania is used when
symptoms are less severe and of shorter duration.6 In ICD-10,
hypomania is characterised by a ‘persistent mild elevation of mood…
not accompanied by hallucinations or delusions’.3 In DSM-IV-TR, a
Table 2. Signs and symptoms of hypomania and mania
include the following types of behaviour which are out
of character for the individual6
t
Feeling energised and ‘wired’
t
Inflated sense of self importance or of one’s abilities
t
Excessively seeking stimulation
t
Overly driven in pursuit of goals
t
Needing less sleep
t
Irritable if stopped from carrying out ideas
t
Disinhibited and flirtatious
t
Offensive or insensitive to the needs of others
t
Swearing more than usual
t
Spending money in an unusual manner or inappropriately
t
Indiscrete and disregarding social boundaries
t
Poor self regulation
t
Making excessively creative and grandiose plans
t
Difficulty discussing ideas rationally or maturely
t
Reporting enhanced sensory experiences
Reproduced with permission from The Medical Journal of Australia
CASE 2
hypomanic episode is of shorter duration than a manic episode (at
least 4 days compared to 7 days), and is not associated with marked
impairment in functioning.4 Note that mood must be persistently
elevated for at least several days on end.3,4 Case 1, Answer 6 outlines
the differences between mania and hypomania.
ANSWER 4
Full blood count, electrolytes, urea, creatinine, liver function and
thyroid function tests should be done to screen for medical conditions
that might cause or exacerbate symptoms, and to assess baseline
results before considering pharmacotherapy. Fasting lipids and fasting
glucose should also be done as a baseline before consideration of
pharmacotherapy. In some cases further investigations might be
required (eg. computerised tomography, magnetic resonance imaging
[MRI] or an electroencephalogram).17
Continued monitoring of serum glucose, lipids, weight, waist
circumference/waist-hip ratio, blood pressure, and smoking status are
indicated. These should be monitored regularly in any patient at risk.
For patients on psychotropic medications, monitoring of metabolic
and cardiovascular risk factors should as a minimum take place at
baseline, 3 months, and 6 months. If there have been no changes over
12 months and there are no other risk factors, monitoring can occur
every 12 months thereafter. Monitoring should be more frequent after
commencement of new medication, changes in medication, or if there
are other metabolic or cardiovascular risk factors such as weight gain
or a family history of diabetes. Sue should also have a routine breast
screen and Pap smear if these have not been done within the last
2 years.
As well as this Sue will also need a thorough physical examination.
ANSWER 5
When to refer to a psychiatrist or public mental health service depends
greatly on a patient’s presentation, the GP’s experience, the support
available from psychiatric services, and the patient’s preference. In
Sue’s case, as this is her first presentation of symptoms suggestive
of possible bipolar disorder, referral to a psychiatrist is recommended.
Some reasons for referral from the National Institute for Health and
Clinical Excellence (NICE) guidelines in the United Kingdom are shown
in Table 3.
ANSWER 6
People with bipolar II disorder usually seek help only for depressive
episodes. This is probably in part because hypomanic episodes
are often not perceived by the patient as abnormal. Patients may
experience mood elevation as constructive and enjoyable.6,18
ANSWER 7
While hypomanic episodes are by definition less severe than manic
episodes, the overall course of bipolar II disorder is associated with
substantial morbidity that is often no less severe than bipolar I.
High rates of occupational, leisure and relationship dysfunction are
common, and bipolar II disorder may be more recurrent than
11
CASE 2
bipolar I (ie. patients tend to have a greater total number of
episodes). Furthermore, bipolar II disorder is associated with
increased morbidity if it becomes chronic, is undiagnosed or
inappropriately treated.19
ANSWER 8
Depression is the main source of disability in bipolar I and II.
Depressive symptoms typically affect up to 30–50% of the patient’s
life, while manic symptoms affect about 5–10%.18
ANSWER 9
The Resources section lists a number of useful sources of information
that can help patients as well as practitioners. It is helpful to ask patients
what they have looked up and actively discuss this with them.20
ANSWER 10
Psychological treatments help reduce the risk of relapse and can
therefore be helpful even to euthymic patients. While CBT is an effective
treatment in many patients with bipolar disorder, particular approaches
don’t suit some patients. So in Sue’s situation, she may wish to try
other psychological strategies. Possibilities for Sue include:10
t
further psychoeducation
t
interpersonal and social rhythm therapy
Table 3. Some reasons for referral21
t
Primary care clinicians should urgently refer to specialist mental health
services, patients with mania or severe depression who are a danger to
themselves or other people
t
When a patient with existing bipolar disorder registers with a practice,
the GP should consider referring them for assessment by a psychiatrist
or specialist mental health service
t
When a patient with bipolar disorder is managed solely in primary care,
an urgent referral should be made:
– if there is an acute exacerbation of symptoms, in particular the
development of mania or severe depression
– if there is an increase in the degree of risk, or change in the nature of
risk, to self or others
– if there are psychotic symptoms
t
When a patient with bipolar disorder is managed solely in primary care, a
review by a psychiatrist/public mental health service or increased contact
in primary care should be considered if:
– the patient’s functioning declines significantly or their condition
responds poorly to treatment
– treatment adherence is a problem
– comorbid alcohol and/or drug misuse is suspected
– the patient is considering stopping prophylactic medication after a
period of relatively stable mood
t
Specialist treatment is usually required in cases with comorbid
psychiatric conditions, mixed episodes or rapid cycling, and where there
is failure to respond to treatment
t
Specialist input will also be needed in new diagnoses, if there is
uncertainty regarding the diagnosis and may be needed in cases with
significant medical comorbidity
Adapted and reproduced with permission from The Royal College of
Psychiatrists, London
12
check Bipolar disorders
t
couples therapy (if she reunites with her partner)
t
group therapy.
It is useful to ask patients to describe any psychological interventions
they have had in the past, and what aspects of these they
found helpful. Some patients appreciate being told about the
characteristics of different modalities as well as the potential benefits
and risks so that they can make an informed decision about what
type of treatment they would like to engage in.
ANSWER 11
Sue should be informed of the symptoms and signs of lithium
toxicity.
The appropriate pretreatment tests include thyroid and renal
function, serum calcium and electrocardiogram.
Monitoring of lithium treatment should include:
t
serum lithium level every 3–6 months once a stable level is
achieved (aim for 0.6–0.8 mmol/L for maintenance therapy)12,17
t
serum urea and creatinine every 3–6 months
t
thyroid stimulating hormone, serum calcium, weight at 6 months
then annually.
Lithium can cause hypothyroidism and hyperthyroidism,
hyperparathyroidism, and renal impairment.12,22
Lithium toxicity can cause:
t
ataxia
t
nausea/vomiting
t
diarrhoea
t
coarse tremor
t
disorientation
t
dysarthria
t
muscle twitches
t
impaired consciousness
t
acute renal failure
t
even death.22
ANSWER 12
There is a risk of rebound mania if lithium is ceased abruptly.
ANSWER 13
Although there may be an increased risk of depressive symptoms
around the time of menopause, and sex hormones may play a role in
the pathophysiology of some psychiatric disorders, there is currently
no clear evidence for the benefit of HRT on these symptoms.15
Pharmacological treatment of psychiatric illness should be managed
in the same way as it would in any other patient. Similarly, decisions
about prescribing HRT should be made as they would be for women
without psychiatric illness. There are circumstances in which HRT
may have a role in the treatment of psychiatric symptoms, but
decisions on this are limited to specialist practice.
check Bipolar disorders CASE 3

QUESTION 3
CASE 3
How would you clarify Sally’s diagnosis?
SALLY HASN’T BEEN HER USUAL SELF
Sally, 23 years of age, is a single university student.
She recently moved out of home and is living
with a flatmate. She was taken to the emergency
department by friends after she cut her foot on
some glass at a nightclub.
Sally’s friends say they have been worried because
she has been:
t
excessively social over the past month
t
neglecting her studies
QUESTION 4
t
bringing men home for sex (she is usually very shy)
Sally’s father has bipolar disorder. How does this affect her risk of
t
spending excessive amounts of money
developing bipolar disorder?
t
getting very little sleep
t
very angry when it was suggested she ‘slow down’.
Sally is skimpily clad in bright, revealing clothes,
with garish makeup. She is coquettish and has
pressured speech. She says that she has been
feeling very depressed, so has been smoking
cannabis daily and has used intravenous
amphetamines twice in the last month. Her father
has bipolar disorder.
FURTHER INFORMATION
After Sally’s foot is sutured, she becomes abusive and starts
QUESTION 1 yelling in the emergency department. Physical examination
What is your differential diagnosis for Sally’s presentation? and investigations are normal apart from cannabinoids in
her urine. She is admitted to the acute psychiatry ward.
She settles on an atypical antipsychotic and sodium valproate.
She is discharged 2 weeks later.
Two months after this she presents to you as her GP, having
become depressed. She has recommenced smoking marijuana
on a daily basis and is drinking 6–8 standard drinks every
other day. She also thinks she might be pregnant.

QUESTION 5
List some of the aspects of Sally’s physical health which you need
QUESTION 2 to address.
Could cannabis do this? What effects does cannabis have on mood?

13
CASE 3
QUESTION 6
What are the problems associated with sodium valproate in this
patient? What other medication strategies might you consider?
QUESTION 7
How would you address Sally’s ongoing substance use?
QUESTION 8
What are the stages of behavioural change? How would you
structure the questions you ask about a patient’s stage of change?
What intervention would you consider for each stage?
14
check Bipolar disorders
QUESTION 9
If Sally was not pregnant what approaches could you use to treat
Sally’s depression?
CASE 3 ANSWERS
ANSWER 1
The differential diagnosis is:
t
manic or mixed episode of bipolar disorder
t
hypomanic episode
t
substance (cannabis or amphetamine) precipitated mood or
psychotic disorder
t
mood disorder or psychotic disorder due to a general medical
condition
t
schizophrenia
t
schizoaffective disorder.
ANSWER 2
Acutely, one of the most characteristic effects of intoxication
with Cannabis sativa is euphoria.23 In people who use cannabis
frequently or are cannabis dependent, rates of depression are
elevated, although there does not appear to be an increased risk of
depression associated with infrequent cannabis use. There are no
systematic studies of cannabis and bipolar disorder.24
In Sally’s case, marijuana intoxication itself is not an adequate
explanation for her symptoms. A drug precipitated mood disorder
(mania) is possible, ie. she has underlying bipolar disorder that was
triggered or exacerbated by cannabis use.
Drug and alcohol use comorbidity is common in people with bipolar
disorder. Furthermore, bipolar disorder is frequently associated
with other comorbid psychiatric conditions. Anxiety disorders
such as obsessive compulsive disorder are particularly common.
Comorbid conditions worsen the outcome of bipolar disorder.25
They should be screened for and treated.
check Bipolar disorders
ANSWER 3
Sally’s diagnosis could be clarified by considering the possibility of
substance-induced symptoms – resulting from intoxication, chronic
use or withdrawal (Table 4), or a nonsubstance-induced disorder –
and employing direct questioning toward this.
ANSWER 4
Affective disorders tend to aggregate in families. Relatives of
bipolar sufferers have an increased risk of both unipolar depression
and bipolar disorder. The risk of first degree relatives of those with
bipolar disorder developing the condition is about 5–10 times that
of the general population.26
ANSWER 5
The following aspects of Sally’s physical health need to be
addressed.
t
Pregnancy testing and contraception – given that many
pregnancies are unplanned, it is important to discuss the
possibility of pregnancy and contraception options with all
women with possible bipolar disorder. One should plan in
advance for pregnancy wherever possible so that adequate
support and medical review can be ensured. Various
contraceptive options are available including condoms, the
contraceptive pill (in the appropriate dose) and etenogestrel
implant, with the latter being a suitable option where compliance
may be a problem
t
Prevention of sexually transmitted infections including use of
condoms and screening for sexually transmitted infections
including tests for chlamydia and gonorrhoea (a first pass urine
for polymerase chain reaction [PCR] or endocervical swabs for
PCR – endocervical swabs should not be taken in pregnancy)
and trichomonas (a high vaginal swab) and serology for hepatitis
B (HepBsAg, HepBsAb) hepatitis C, HIV and syphilis (rapid
plasma reagin)
t
Drug use – this is discussed further in Answer 7 and 8 of this
case.
Addressing aspects of Sally’s health may proceed concurrently
with addressing aspects of her psychiatric condition.
ANSWER 6
Sodium valproate is teratogenic. It is therefore best not to use it
first line in women of child bearing potential. There is a 1–5% risk
of neural tube defects compared to a population risk of 0.03%.
Facial and cardiac malformations can also occur. Folic acid
supplementation is recommended.27 Other side effects of sodium
valproate include weight gain, transient hair loss, and rarely, hepatic
toxicity. It is also associated with polycystic ovarian syndrome.12,22
No pharmacotherapy for bipolar disorder is risk free during
pregnancy, and no psychotropic medications have been thoroughly
studied with regards to safety in pregnancy and lactation.
First generation antipsychotics may confer a lower foetal risk
CASE 3
Table 4. Substance-induced symptoms28
Substance-induced symptoms can result from intoxication,
chronic use or withdrawal
t
Intoxication with cannabis can produce a transient, self limiting psychotic
disorder characterised by hallucinations and agitation
t
Prolonged heavy use of psychostimulants (eg. amphetamine,
methylenedioxymethamphetamine [MDMA]) can produce a psychotic
picture
t
Hallucinogen induced psychosis is usually transient, but may persist if use
is sustained
t
Heavy alcohol use can be associated with alcoholic hallucinosis and
morbid jealousy
t
Psychotic symptoms can also occur during withdrawal (eg. delirium
tremens) and delirious states
t
A nonsubstance-induced disorder should be considered when:
– symptoms precede the onset of substance use
– symptoms persist for longer than 1 month after acute withdrawal or
severe intoxication
– symptoms are not consistent with the substance used
– there is a history of symptoms during periods
(greater than 1 month) of abstinence
– there is a personal or family history of a nonsubstance-induced
psychiatric disorder
Adapted and reproduced with permission from The Medical Journal of Australia
than lithium or anticonvulsants, although there is inadequate data
for many agents. There is inadequate data available for second
generation antipsychotics, although gestational diabetes has been
associated with olanzapine. Lithium is associated with a risk of
Ebstein abnormality of about 1 in 1000, compared to the general
population rate of 1 in 20 000. Carbamazepine carries a risk of
neural tube defects of about 1%. It is also associated with facial
malformations, and developmental delay.27
Women with a history of bipolar disorder are particularly vulnerable
during pregnancy and the postpartum. Untreated bipolar disorder puts
both the mother and foetus at risk, but at the same time all psychotropic
drugs have the potential to affect the foetus.
The management of bipolar disorder during pregnancy is best decided
on a case-by-case basis after evaluation of the risk/benefit ratio for
each individual.
Bipolar disorder in pregnancy requires specialist (psychiatric)
management in collaboration with the GP, obstretrician, midwife and
psychological care.
ANSWER 7
Addressing Sally’s ongoing substance abuse involves establishing
rapport and a good therapeutic alliance, educating her about the
effects of her substance use and its link to her current psychological
symptoms, treating her mood disorder, assessing her motivation for
change, referral to the appropriate services, discussing triggers for
relapse and discussing relapse prevention. Table 5 lists these principles
of management for a GP involved in the care of a patient with ongoing
substance use.
15
CASE 3 check Bipolar disorders

ANSWER 8
The stages of behavioural change are precontemplation,
contemplation, preparation, action, maintenance and relapse.
Questions can be structured around each of these stages. It is
importance that the questions are open ended, nonjudgemental, and
actively involve the patient to participate in their own decision making
in each of these stages. The type of intervention varies depending on
the stage of Sally’s behavioural change. Education is appropriate at
the precontemplation phase, exploring the pros and cons of change
is appropriate at the contemplation stage, determining strategies for
change is appropriate at the preparation stage, assisting the patient
with implementation is helpful at the action phase, reviewing relapse
prevention strategies is important at the maintenance phase and
assisting in change is relevant at the relapse stage. Table 6 outlines
the stages of change involved in altering certain behaviours and
the interventions a health professional can undertake to support a
patient through the change in that behaviour.
ANSWER 9
Approaches to deal with Sally’s depression include the following.
t
Dealing with Sally’s illicit drug and alcohol use, first with the
strategies described above, before altering her prescribed
medication then assessing her residual depressive symptoms once
she has not been using illicit drugs for a period of time
t
Dealing with her depression concurrently, as depression can
predispose an individual to use illicit drugs and alcohol in an
attempt to relieve their symptoms
t
Checking compliance with, and optimising dosage of, her current
antipsychotic and sodium valproate
t
Considering the use of psychological strategies such as supportive
psychotherapy, CBT, interpersonal and social rhythm therapy
t
Providing advice regarding diet, physical exercise and sleep routine.
Table 5. Principles of management of patients with
comorbid substance misuse28
t
First engage patients, adopting a nonjudgmental attitude
t
Educate the patient:
– give general advice about harmful effects of substance misuse
– advise about safe and responsible levels of substance use
(eg. National Health and Medical Research Council guidelines for safe
alcohol use)
– help the patient understand and appreciate links between substance
misuse and symptoms (eg. cannabis use and mood changes)
– inform the patient about safe practices (eg. using clean needles, not
injecting alone, practicing ‘safe sex’)
t
Treat mood disorder and monitor the patient for potential side effects
t
Help the patient establish advantages and disadvantages of current use,
and motivate the patient for change
t
Evaluate the need for concurrent substance-use medications
(eg. methadone, acamprosate, nicotine replacement therapy)
t
Refer the patient to relevant clinical and community services as
appropriate
t
Devise relapse prevention strategies that address both mental illness and
substance misuse
t
Identify triggers to relapse (eg. meeting other drug users, being paid,
family conflict) and explore alternative coping strategies. It is important to
identify triggers for both substance use and mood episodes, and to show
links between these where they exist
Adapted and reproduced with permission from The Medical Journal of Australia

FEEDBACK
An antidepressant is sometimes added to a medication
regimen that consists of a single prophylactic medication.
Adding an antidepressant could cause cycle acceleration (ie.
frequent exacerbations of bipolar disorder) so if this option is
pursued, it is recommended that the patient be referred to a
psychiatrist, be closely monitored and that consideration be
given to withdrawing the antidepressant within 1–2 months of
successful resolution of bipolar depression.
Note that antidepressant monotherapy is not recommended in the
bipolar disorders because of the risk of inducing rapid cycling.

16
check Bipolar disorders CASE 3

Table 6. Stages of change and interventions28,29

Stage of change Characteristics Questions to the patient Intervention

Precontemplation t
Not thinking about change t
What warning signs would let you know t
Educate patient about substance
Goal: patient to begin t
May be resigned that this is a problem? misuse
thinking about change t
Feeling of no control t
How will you know when it is time to quit? t
Help the patient to examine problems
t
Have you tried to change in the past? with their current behaviour
t
Denial – does not believe it applies
to self
t
Believes consequences are not
serious

Contemplation t
Weighing benefits and costs of t
Why do you want to change at this time? t
Explore ‘pros and cons’ of change
Goal: patient to examine behaviour and proposed change t
What were the reasons for not changing? t
Acknowledge patient’s ambivalence
benefits and barriers to t
What are the barriers today that keep you and resistance to change
change from change?
t
What might help you with those aspects?
t
What things (eg. people, programs and
behaviours) have helped in the past?
t
What would help you at this time?

Preparation t
Experimenting with small changes t
Have you tried doing anything differently? t
Help patient to determine the most
t
What do you think has been helpful, or appropriate strategies for change
unhelpful?
t
Are there other things that you would be
interested in trying, or hearing about?
t
What has worked in the past? Would you
like to try this again?
t
Would you like to discuss some of the
other options available (eg. psychological
treatments, medications, programs)?

Action t
Taking a definitive action to change t
Do you have any questions about this t
Assist patient to instigate planned
action? changes
t
How have things been going with this
action?
t
What aspect of this action have you found
most effective?

Maintenance t
Maintaining new behaviour over t
Could you tell me about some prevention t
Encourage new skills
time strategies you’ve learned? t
Rehearse relapse revention strategies
t
Have there been any times where you were
close to using again?
t
Could we talk about ways of dealing with
these times should they arise again?
t
What strategies are working well? Maybe
you could write these down so that you can
remember them in case you have a lapse.

Relapse t
A normal part of the process of t
(A lapse is very common. In fact, most t
Support patient
change people who eventually recover from drug t
Assist in renewing process of change
t
Usually feels demoralised or alcohol use lapse at least once.) How do
you feel about your use now?

17
CASE 4 check Bipolar disorders

FURTHER HISTORY
CASE 4 Sam is provisionally diagnosed with a major depressive
SAM LOST HIS JOB episode and commenced on escitalopram 10 mg at morning.
On review 1 week later, his symptoms are worse. In particular,
Sam is 24 years of age. He is a labourer who is
he feels more irritable but is still having periods where he feels
currently on unemployment benefits. Since he lost
‘very good’. He is sleeping less, now only 3 hours per night.
his job 2 months ago he has been feeling irritable.
His thoughts are ‘more racy’.
His mood has been ‘going up and down’, from
feeling depressed to feeling ‘really good’. At the
QUESTION 2
time of presentation he is not enjoying anything
in life and feels worthless. He has a decreased How does this information change your differential diagnosis?
need for sleep. His thoughts have been racing. He
feels hyperactive, can’t concentrate, and is easily
distracted. He is more talkative than usual, he has
lost a few kilograms in weight and has had some
thoughts that life is not worth living but has no
suicidal plans or intent.
Sam lost his job due to altercations with his
colleagues and boss, and broke up with his
girlfriend of 6 months shortly afterwards.
Further questioning reveals longstanding episodes
of irritability of mood. Similar to the current episode,
these are characterised by sustained irritability,
FURTHER INFORMATION
hyperactivity, overspending, and a decreased need
for sleep. These symptoms last for weeks and Sam is referred to a psychiatrist and diagnosed with bipolar
are followed by depression, which lasts weeks to disorder, mixed episode. The selective serotonin reuptake
months. inhibitor (SSRI) is stopped, and sodium valproate 400 mg twice
per day is commenced.
He has a background of longstanding alcohol use
and increasing use of intranasal speed which ‘helps Over the next few weeks, his irritability, talkativeness, and
mood and concentration’. racing thoughts settle. Dominant depressive symptoms remain,
consistent with a major depressive episode. In particular, Sam
He never really got on with others at school and
complains of poor sleep. As Sam’s GP, you discuss this with
dropped out at age 15. He describes himself as ‘just
the psychiatrist, who suggests that quetiapine 200 mg at night
hopeless’ at academic work.
be added.
He has had warnings for domestic violence and pub
Sam visits again and says that his mood ‘is generally good
fights, and lost his driver’s licence for speeding.
now’, he feels calmer and his sleep has returned to normal,
but he still can’t concentrate on things. He says his poor
concentration and distractibility are longstanding. He says
QUESTION 1 he read something about adult attention deficit hyperactivity
What is your differential diagnosis for Sam’s presentation? disorder (ADHD) in a magazine and asks if he might have this.

QUESTION 3
Could this be adult ADHD? How would you differentiate between
bipolar disorder and ADHD?

18
check Bipolar disorders
FURTHER HISTORY
Since he started school Sam has always had attention
problems. He never really managed any school subjects and
was held back in year 2. Then he just ‘pushed through’ until he
left school at age 15. He was always a fidgety child, and ‘never
sat still’. He was a risk taker and ‘always in trouble’.
QUESTION 4
How might you attempt to further support a diagnosis of adult ADHD?
QUESTION 5
What is the relationship between bipolar disorder and ADHD in
adults?
QUESTION 6
What further treatment options might you consider and what are the
risks and benefits?
CASE 4
FURTHER INFORMATION
Sam is commenced on methylphenidate 10 mg per day by his
psychiatrist (who has a special interest in adult ADHD), increasing
daily to maximum effect. Stimulant prescription is commenced
on the condition that he have regular urine drug screens for illicit
substances given his history of use. Valproate and quetiapine
are continued. He is referred for neuropsychological testing to
further elucidate his deficits related to ADHD, so that these can
be targeted specifically with the aim of maximising his
socio-occupational functioning. He tolerates methylphenidate
well, with sustained ‘even’ mood and marked improvement in
attention. However, if he misses quetiapine, he finds that he has
trouble sleeping and becomes ‘cranky’.
QUESTION 7
What nonpharmacological treatments would be useful to Sam?
CASE 4 ANSWERS
ANSWER 1
The differential diagnosis is:
t
major depression with irritability
t
anxiety disorder
t
substance-induced mood disturbance
t
bipolar disorder (mixed episode)
t
adjustment disorder
t
adult ADHD
t
cluster B personality disorder/traits.
ANSWER 2
The exacerbation of symptoms makes a mixed episode more likely.
A mixed episode is defined as a period of at least 1 week where
symptoms of both a manic episode and a major depressive episode
are present nearly every day. Symptoms of mania were present
in the initial presentation, including a decreased need for sleep,
increased talkativeness, subjective experience that thoughts are
racing, and distractibility.
19
CASE 4 check Bipolar disorders

ANSWER 3 of childhood ADHD must be obtained, beginning with a good

A good history is key (Table 7 and 8 ) in determining the cause of developmental history. Reviewing Sam’s school records and
poor concentration or distractibility, and can prevent an iatrogenic interviewing his parents would be helpful.
exacerbation of symptoms that may occur with inappropriate therapy. A rating scale may also help (eg. Wender Utah Rating Scale,32 Conners
Adult ADHD Rating Scale33).
ANSWER 4 It is important to confirm that ongoing inattentiveness and hyperactivity
The diagnosis of adult ADHD is controversial, but it appears that a has occurred in the absence of drug use.
subset of children with ADHD go on to have symptoms as adults, with
significant social and occupational consequences.30,31 ANSWER 5
Note that ADHD does not tend to develop in adulthood without There is little research in this area, and it is unclear what relationship
preceding symptoms of ADHD in childhood. Evidence suggestive (if any) exists between ADHD and bipolar disorder.35 Nonetheless
some epidemiological evidence suggests that they do co-occur more
commonly than would be expected by chance. One study showed a
Table 7. Diagnostic symptoms of a manic episode and
lifetime prevalence of ADHD of 9.5% in people with bipolar disorder.36
ADHD34
Manic episode ADHD Degree of overlap
ANSWER 6
Psychomotor agitation Hyperactivity Extensive
Sam can be provided with details of available stimulants. The potential
Impulsive Impulsivity Extensive
risk of a manic switch with stimulants should be discussed (although
Distractibility Inattention Extensive this would be lower if he was also on a mood stabiliser).
Irritability Ubiquitous Extensive Some general management tips for people with comorbid ADHD and
More talkative Talks too fast Moderate bipolar disorder are listed in Table 9.
Elation – Little Information about medications for ADHD can be found in the Australian
Grandiosity – Little Medicines Handbook37 and Therapeutic Guidelines.22
Flight of ideas/racing thoughts – Little
Decreased need for sleep Difficulty settling Little ANSWER 7
for sleep Little research has been carried out on psychosocial treatment of
Increased goal-directed activity – Little ADHD in adults. Residual symptoms in people on pharmacotherapy are
Excessive pleasurable activities – Little common, and CBT-based approaches that target deficits in planning,
(eg. hypersexuality) organisation and attention, and include psychoeducation may help.38
Reproduced with permission from Springer Psychological treatments for Sam’s drug and alcohol comorbidities
should also be implemented (eg. motivational interviewing,39 as well as
psychological treatments aimed at bipolar disorder).10
Table 8. Diagnostic symptoms of bipolar depression
and ADHD34
Bipolar depression ADHD Degree of
overlap
Table 9. The sequential initiation of treatment for
patients with bipolar disorder and concurrent ADHD34
Depressed mood Dysphoria Extensive
t
Remove the offending agent
Insomnia Difficulty settling Extensive
– stimulants (if you cannot completely discontinue, try for ‘drug
Irritability Irritability Extensive holidays’ – short breaks)
Difficulty concentrating Inattention Extensive – antidepressants
Psychomotor agitation Hyperactivity Moderate – benzodiazepines
Disinhibition Impulsivity Moderate t
Maximise antimanic treatments
Weight loss/gain Weight loss with Moderate (after – use adequate blood levels and doses
stimulants stimulant treatment) t
Attempt to reintroduce the stimulant only after the mood is stabilised and
Psychomotor retardation – Little it has been demonstrated that such treatments continue to be indicated.
If you cannot wait, remember that it is likely to delay the treatment
Fatigue or loss of energy – Little
response time for the antimanic
Hypersomnia – Little
t
Try to ‘kill two birds with one stone’ when possible (eg. use agents that
Loss of interest or pleasure – Little may improve more than one pole of bipolar disorder)
Thoughts of death/suicidality – Little t
Consider discontinuation of stimulants periodically
Reproduced with permission from Springer Reproduced with permission from Springer

20
check Bipolar disorders
CASE 5
IS MRS SMITH DEPRESSED?
You have just taken over the care of patients in a local
nursing home from a GP who retired. The nursing staff ask
you to see Gladys Smith, a 70 year old lady who is in low-
level care.
Mrs Smith moved to the nursing home 1 month ago, after
being discharged from an old age psychiatry unit. Before
her admission, she had been living independently. The
immediate precipitant for her admission was a fire in her
flat. When the fire department arrived, Mrs Smith was
running around the perimeter of the building claiming that
she was the Messiah and that the blaze was started by
demons. She was taken to hospital, diagnosed with a manic
episode and transferred to the old age psychiatry unit.
Basic blood tests, including thyroid function, B12, folate,
and syphilis serology were normal. A cerebral MRI showed
mild generalised atrophy thought to be consistent with age
related changes. There was also evidence of small vessel
ischaemia. She was commenced on lithium. When her manic
symptoms resolved, she had occupational therapy and
neuropsychological assessments. Mini Mental State Exam
(MMSE) was 25/30. She was found to have mild executive
functioning and verbal memory deficits. It was felt that she
needed supported accommodation because of decreased
mobility due to osteoarthritis, and she was approved for low-
level care. Mrs Smith initially settled into the nursing home
well. She socialised with the other residents and participated
in activities.
Mrs Smith has had one previous psychiatric admission
15 years ago for a manic episode and at that time was
QUESTION 1
What is the differential diagnosis for Mrs Smith’s presentation? What
is the most likely diagnosis?
CASE 5
commenced on lithium but ceased taking this after
discharge.
She is currently taking lithium 500 mg twice per day as well
as paracetamol 1 g four times per day and celecoxib 100
mg twice per day, which were commenced 3 weeks ago for
osteoarthritic pain. There is no other known medical history.
Over the past 2 weeks, Mrs Smith hasn’t been eating much
and has been spending much of the day lying in bed. The
nursing staff think she has lost some weight. She has been
seen wandering the halls at night on a few occasions. She is
agitated and seems confused. On one occasion she asked the
staff, “Are the Russians here yet?” One of the nurses thinks
Mrs Smith has been seeing things.
You are asked by staff if you think she is depressed. You
examine Mrs Smith.
She is confused and able to provide only a limited account of
things but says that she feels nauseated and has had some
diarrhoea.
An MMSE is 12/30:
t
not oriented to time or place
t
scores 0/5 for serial 7s
t
0/3 for three item recall.
Heart rate, respiratory rate, blood pressure, temperature and
oxygen saturation are within normal limits. She has a coarse
tremor of her hands. Oral mucosa is mildly dry. There are
osteoarthritic changes in her upper and lower limbs. Pinprick
blood sugar is 5.1 mmol/L. Otherwise, cardiovascular,
gastrointestinal, respiratory, and neurological examinations
are normal. A serum lithium level is 1.5 mmol/L; urea,
electrolytes and creatinine are normal.
QUESTION 2
Is it possible that Mrs Smith has dementia? How could you tell?
21
CASE 5 check Bipolar disorders

QUESTION 3
CASE 5 ANSWERS
What is your short term management plan?

ANSWER 1
Differential diagnoses in this scenario include delirium, dementia and
depression. Delirium secondary to lithium toxicity is the most likely
cause of this presentation. Note that delirium is often misdiagnosed
as depression.40–42 Lithium toxicity can occur at lower levels in the
elderly than in a younger population, even at supposedly therapeutic
levels (see Answer 4).
The recently commenced celecoxib could have caused this.
Angiotensin converting enzyme inhibitors, diuretics, and nonsteroidal
anti-inflammatory drugs can increase lithium levels. Lithium toxicity
can also be caused by reduced fluid intake, fluid loss from vomiting,
diarrhoea or excessive sweating, or by deliberate or inadvertent
overdose.22
It is essential to consider delirium in differential diagnosis in an
elderly person who is presenting with emotional, cognitive, or
QUESTION 4 behavioural symptoms, especially if they are of abrupt onset.
Over the longer term, what monitoring and follow up should Mrs
Smith have? ANSWER 2
The clinical distinction between delirium and dementia can be
complicated.
Dementia is the main risk factor for delirium. Two-thirds of cases of
delirium occur in patients with dementia.40 It would be reasonable
to consider the possibility of underlying dementia once the cause
of Mrs Smith’s delirium has been treated, but dementia would not
account for her acute change (Table 10).

Table 10. Clinical features of delirium verses dementia

Feature Delirium Dementia
Onset Rapid Insidious
Primary deficit Attention Short term memory
Course Fluctuating Progressive

QUESTION 5 Duration Days to weeks Months to years

Are psychological treatments for bipolar disorder indicated in the
elderly? Would these be helpful for Mrs Smith?
Consciousness Clouded Clear
Delirium is common and is frequently missed. It is an important
nonspecific sign that often heralds the development of a life
threatening illness. It includes the following features.
t
It typically has an acute onset and tends to fluctuate, and is often
worse at night
t
Inattention and sleep-wake cycle disturbances – these may be the
most frequent findings41
t
Other common features include a disturbance of consciousness,
cognitive impairment, perceptual disturbance, disorganised
thinking, emotional/behavioural disturbances
t
Orientation alone is an insufficient screening test, this may be the
least frequent cognitive deficit.41

22
check Bipolar disorders
There are hyperactive and hypoactive forms of delerium. The
hypoactive form is more common in the elderly, and is often
missed. Mild states are also often missed, especially by those not
familiar with the patient’s usual intellectual performance. Differential
diagnoses include dementia and mood disorders, especially
depression (delirium is often misdiagnosed as depression).40–42
Almost any physical illness can give rise to delirium in the elderly.
Common causes include medications, infections, metabolic and
endocrine derangement, cardiovascular disease, respiratory
disease, intracranial pathology, gastrointestinal disease, metabolic
derangement, and alcohol withdrawal. A broad differential diagnosis
should be considered, and a thorough physical examination is
essential.
Some common misunderstandings about delirium are listed in
Table 11.
Table 11. Common misunderstandings about delirium41
t
The typical presentation is of delirium tremens (ie. agitated, floridly
psychotic)
t
More severe delirium is associated with a greater degree of hyperactivity
t
Quiet and well behaved patients are generally cognitively intact
t
Older people are normally forgetful and easily disoriented
t
Irritability or vagueness often reflects personality rather than an altered
mental state
t
Patients are offended by tests of cognition
t
A patient’s level of orientation and cognitive function are consistent over
24 hours
t
Delirium rarely responds to treatment in those with underlying advanced
disease
Modified and reproduced with permission from The Royal College of
Psychiatrists, London
ANSWER 3
Delirium is a medical emergency. Lithium toxicity can be fatal. Mrs
Smith should be transferred immediately to the nearest emergency
department via ambulance. You or the nursing home staff should
inform her relatives.
Lithium toxicity is treated by withdrawal of lithium, intravenous fluid
resuscitation, and electrolyte replacement, as well as treatment
of any underlying medical condition. Haemodialysis may be
needed.22,43
ANSWER 4
Regular monitoring of lithium levels, renal function, and thyroid
function should be undertaken:
t
creatinine clearance can decrease with age, affecting serum
lithium levels
CASE 5
t
recommended lithium ranges for acute mania are usually
0.8–1.2 mmol/L. Lower ranges (eg. 0.6–0.8 mmol/L) are
recommended for maintenance treatment. Toxicity occurs at
levels >1.5 mmol/L, but can occur at ‘therapeutic levels’ in the
elderly. Levels >3.5 mmol/L are potentially lethal.22 There is not
much data upon which to guide serum levels in older adults, but
levels of 0.5–0.8 mmol/L are often recommended.17
Over the longer term, monitor for cognitive decline (Mrs Smith had
some mild deficits when neuropsychological testing was done in her
first hospitalisation).
Assessment for vascular risk factors:
t
monitor blood pressure
t
check fasting lipids
t
monitor weight, waist circumference, waist to hip ratio and BMI
t
Mrs Smith’s recent blood sugar level was normal, but you should
consider checking this again in the future.
Mrs Smith should also be monitored for signs and symptoms of
major depression or mania.
ANSWER 5
Psychotherapy is effective in older people but is frequently not
offered.44
Psychological approaches can also be helpful for patients with
cognitive impairment, although the approach needs to be modified.
In such cases it would be wise to consider referral to someone with
experience in providing therapy to people with cognitive impairment,
such as an old age psychiatrist (psychogeriatrician), or a psychologist
with relevant training and experience.
With respect to Mrs Smith’s current state, psychological
interventions (aside from those aimed at assisting reorientation) are
clearly contraindicated in delirium. Once her delirium has settled, it
would be sensible to provide some psychoeducation to Mrs Smith,
and the nursing staff at the aged care facility. In particular, it would
be useful to ensure the nursing staff understand:
t
early warning signs of depression, mania, and delirium
t
what to do if she appears to be relapsing into mania or
depression, or if she appears to be delirious.
In the future, if she relapses into mania or depression, more
extensive psychotherapeutic treatment should be considered.10
23
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check Bipolar disorders
PROFESSIONAL RESOURCES
t
Bipolar disorder: new understandings, emerging treatments. MJA
Supplement 16 August 2010;193. Available at www.mja.com.au/
public/issues/193_04_160810/contents_suppl_160810.html
t
GP Psych Support Service provides advice for GPs from a
psychiatrist via phone, fax or secure email and is available
24 hours per day, 7 days per week. Tel 1800 200 588
Fax 1800 012 422. Available at www.psychsupport.com.au
t
The Royal Australian and New Zealand College of Psychiatrist’s
Code of Ethics. Available at www.ranzcp.org/resources/conduct-
and-ethics.html
t
Motivational interviewing in general practice. check Program
October 2009;unit 451.
STATE AND TERRITORY OUTREACH OR ON CALL
PSYCHIATRIC SERVICES
24 hour mobile on call psychiatric services are available in most
(but not all) parts of Australia.
Australian Capital Territory
Crisis Assessment and Treatment Team (CATT)
http://health.act.gov.au/c/health?a=sp&pid=1061186615
Tel 1800 629 354 (24 hour service) or 02 6205 1065
New South Wales
Crisis Service/Team or CATT
www.health.nsw.gov.au/mhdao/contact_service.asp
Northern Territory
Alice Springs Community House Crisis Assessment Team
CATT www.health.nt.gov.au
Tel 08 8951 7710 (business hours) or 08 8951 7777 (after hours)
Top End Mental Health Service
Tel 08 8999 4988
Queensland
Mobile Intensive Support Team (MIST/MIT)
Also ACTT/ACS: www.health.qld.gov.au/mentalhealth
South Australia
Assessment and Crisis Intervention Service (ACIS)
www.health.sa.gov.au/mentalhealth
Statewide Emergency Crisis Tel 131 465
Rural and Remote Emergency Triage and Liaison Tel 131 464
Tasmania
CATT www.dhhs.tas.gov.au/mentalhealth
Tel 1800 332 388
Victoria
CATT. Available at www.health.vic.gov.au/search.htm?q=CAT+Team
Western Australia
The Mental Health Emergency Response Line (or Rural Link in rural
areas) takes referrals, the Community Emergency Response Team
(CERT) and Acute Community Intervention Team (ACIT) provide
assessment and treatment. Available at www.mentalhealth.wa.gov.
au Tel 1300 555 788 or 1800 332 388
RESOURCES
RESOURCES FOR PATIENTS AND CARERS
t
SANE Australia: www.sane.org
t
beyondblue: www.beyondblue.org.au
t
Black Dog Institute: www.blackdoginstitute.org.au
t
Victorian Better Health Channel: www.betterhealth.vic.gov.au/
bhcv2/bhcarticles.nsf/pages/Bipolar_disorder?open
t
MoodSwings is an online self-help program for bipolar disorder.
Intake of registrations may vary with time. Information on this site
is also relevant. www.moodswings.net.au
t
Multicultural Mental Health Australia: www.dhi.gov.au/
Multicultural-Mental-Health-Australia/default.aspx.
The following online self management programs are directed at
depression and anxiety, but are applicable to bipolar disorder,
particularly as anxiety is a common comorbidity:
t
Moodgym: www.moodgym.anu.edu.au
t
E-couch: http://ecouch.anu.edu.au
t
Anxiety online: www.anxietyonline.org.au.
STATE AND TERRITORY MENTAL HEALTH ACTS
t
Australian Capital Territory Mental Health (Treatment and Care)
Act 1994. Available at www.legislation.act.gov.au/a/1994-44/
default.asp
t
New South Wales Mental Health Act, 2007. Available at
www.austlii.edu.au/au/legis/nsw/consol_act/mha2007128
t
Northern Territory Mental Health and Related Services Act, 2010.
Available at www.health.nt.gov.au/Mental_Health/Legislation/
index.aspx and www.austlii.edu.au/au/legis/nt/consol_act/
mharsa294
t
Queensland, Mental Health Act, 2000. Available at www.health.
qld.gov.au/mha2000
t
South Australia Mental Health Act, 2009. Available at www.
austlii.edu.au/au/legis/sa/consol_act/mha2009128/index.html
t
Tasmania Mental Health Act, 1996. Available at www.austlii.edu.
au/au/legis/tas/consol_act/mha1996128
t
Victoria Mental Health Act, 1986. Available at www.austlii.edu.au/
au/legis/vic/consol_act/mha1986128/index.html
t
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www.mhrbwa.org.au/publications.
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The editors apologise for any confusion or inconvenience.
25
CHECK CATEGORY 2 QI&CPD ACTIVITY
Bipolar disorder
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activity associated with this unit:
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1800 284 789.
QUESTION 1
Wendy, age 52, presents with a 9 month history of amenorrhoea, mild
hot flushes, decreased libido, irritability and a loss of interest in her
usual activities. She also feels an increased need for sleep and has
gained 6 kg in weight. Your first step in management is to:
A. prescribe hormone replacement therapy (HRT) to treat her
menopausal symptoms
B. discuss the overlap between symptoms of depression and
menopause and suggest a trial of treatment for her depressive
symptoms
C. tell her all women have to go through menopause and it will pass
soon enough
D. prescribe both HRT and an antidepressant from the outset
E. recommend she keep a food and exercise diary and return in
3 months.
QUESTION 2
Susie, 37 years of age, is a patient of yours who presents with acute
mania. You transfer her to hospital. Upon discharge she has been
stabilised on lithium. When treating a patient with lithium:
26
check Bipolar disorders
A. no blood tests are required before giving the first dose
B. baseline thyroid function, renal function, serum calcium
and electrocardiogram (ECG) should be established before
commencing treatment
C. serum urea and creatinine should be checked every 12 months
D. thyroid function tests should be repeated only if symptoms of
hypothyroidism develop
E. lithium toxicity usually only occurs in the first few weeks of
treatment.
QUESTION 3
Susie is stabilised on lithium but forgets to take her tablets away
with her on a 3 month holiday. Your advice when she rings you
from interstate is:
A. resume the same dose she usually takes when she returns
from holidays
B. resume her lithium on a lower dose when she returns, then
C. do not cease her lithium abruptly due to the risk of mania. You
need to help her arrange a supply of medication
D. take a double dose for 2 days when she returns
E. have a trial of not taking her medication while she is away on
holidays as her stress levels will be lower.
QUESTION 4
Fleur is the wife of one of your patients Brett, who is known to
be a regular cannabis user. Fleur presents concerned about her
husband’s behaviour. He has recently been seen apparently talking
to himself and is frequently very agitated. She also suspects
that he may have lost his job, although he has not divulged this
information to her. He appears to be excessively confident about
his new online poker hobby. The possible explanation is:
A. he is experiencing intermittent bouts of cannabis intoxication
B. he has started using other recreational drugs such as
amphetamine
C. he may be experiencing a manic episode as part of an
emerging bipolar disorder
D. he may have an organic neurological illness
E. all of the above.
QUESTION 5
Christie, 35 years of age, is a married woman who has recently
been diagnosed with bipolar disorder and presents with her
husband wishing to discuss her medication in the context of
wanting to start a family in the future. Concerning pharmaceutical
management of this case, you would:
A. use sodium valproate as your drug of first choice
B. advise her to continue her medication until she falls pregnant then
stop immediately as most women feel better during pregnancy
check Bipolar disorders CHECK CATEGORY 2 QI&CPD ACTIVITY

C. discuss the possibility of pregnancy and contraceptive options, QUESTION 9

explaining the potential risks of unplanned pregnancy and When you see Alice she appears a little vague but is oriented to time,
psychotropic medication place and person. The nurse says she was much worse overnight.
D. avoid discussing the possible teratogenic effects of medication as Which of the following is true?
you don’t want to dissuade her from taking her medication A. More severe delirium is associated with a greater degree of
E. advise her that she should have a tubal ligation. hyperactivity
B. Vagueness in this age group is always due to dementia
QUESTION 6 C. A patient’s level of orientation and cognitive function are variable
Sally comes to see you to discuss her son Marcus, age 25. Marcus over a 24 hour period
was recently diagnosed with a manic episode after presenting with D. Quiet and well behaved patients are generally cognitively intact
symptoms of hyperactivity, difficulty concentrating, and excessive
E. After 5 years her lithium will be well tolerated.
spending. Sally brings in an article she found on the internet about
adult attention deficit hyperactivity disorder (ADHD). She asks if this
condition could better explain Marcus’ symptoms. In differentiating QUESTION 10
between ADHD and a manic episode the most useful symptom/s to You look at Alice’s file to see when she last had her lithium level
elucidate are: tested. Regarding lithium monitoring, which of the following is true?
A. elation and grandiosity A. Optimum lithium dose can change with age as creatinine
clearance decreases
B. hyperactivity and impulsivity
B. Recommended serum lithium level for acute mania is
C. distractibility and irritability
0.8–1.2 mmol/L
D. talkativeness
C. Toxicity occurs at serum lithium levels >1.5 mmol/L (or lower in
E. insomnia and hypersomnia. the elderly)
D. More frequent monitoring may be needed if other medications
QUESTION 7
change
You explain to Sally that the diagnosis of adult ADHD is controversial
E. All of the above.
and that it is unclear whether there is any relationship between ADHD
and bipolar disorder. For diagnostic purposes, which of the following
can be helpful?
A. Confirmation of ongoing inattentiveness and hyperactivity in the
absence of drug use
B. Review of school records
C. Interviewing the parents of adult patients
D. Awareness of any issues involving the law or relationship
breakdowns
E. All of the above.

QUESTION 8
You are asked to review Alice Brown, age 70, a nursing home patient
with a past history of manic episodes who has been prescribed lithium
for 5 years. She has a 2 week history of a loss of appetite, social
withdrawal and vagueness. Alice was started on a new medication for
her arthritis 1 month ago. From the history, you suspect a diagnosis
of delirium and plan to review Alice as soon as possible. Which of the
following is false about delirium?
A. It is a rare condition associated with alcohol withdrawal
B. It has an acute onset, often worse at night
C. It is associated with inattention and sleep-wake cycle disturbance
D. It is an important nonspecific sign that often heralds the
development of a life threatening illness
E. It commonly causes a disturbance of consciousness.

27
NOTES check Bipolar disorders

28
 Untypical atypical
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anxiety disorder (GAD): Treatment of generalised anxiety disorder. DOSAGE: Once daily, without food.
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PBS Information: Authority required (STREAMLINED). Maintenance treatment of bipolar I disorder. Monotherapy,
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