Clinical Review - Bipolar disorder

A clinical review of the dianosis and management of bipolar disorder.

Psychoeducation can help the patient manage their condition (Photograph: SPL)
Psychoeducation can help the patient manage their condition (Photograph: SPL)

Section 1: Epidemiology and aetiology
Bipolar disorder affects about 2 per cent of the population, so an average GP list will include about 20-40 patients with the illness. The first onset occurs most commonly in late teens and early 20s. The WHO has estimated that bipolar disorder is the fourth most important cause of worldwide disability in 15-45 year-olds.

Public awareness of bipolar disorder has increased in part due to a number of celebrity sufferers, such as Stephen Fry. There has been an increase in the number of people presenting to primary and secondary care concerned that they have bipolar disorder. Careful assessment is required.

Bipolar disorder is strongly heritable and twin studies have found high concordance rates. So far, only genes of small effect have been identified and it appears these may act as susceptibility genes, shared with other disorders including schizophrenia. Causation is likely to be multifactorial, with genetic susceptibility interacting with environmental stressors leading to acute episodes.

Classification
There is a spectrum of mood variability in the general population and mood disorders are classified according to the nature and severity of the mood disturbance (see figure below).

Bipolar disorder, also known as manic depressive disorder, is classified according to the severity of the manic symptoms:

Type 1: One or more manic episodes, whether or not there has been a depressive episode.

Type 2: One or more depressive episodes and one or more hypomanic episodes.

Bipolar disorder is also classified according to its course. If there are more than four discrete episodes of mania and/or depression per year, this is called rapid cycling.

Section 2: Making the diagnosis
Mood variability, the main feature of bipolar disorder, can be episodic with clear-cut manic and depressive episodes. Over time, the most disabling part of the illness is the depression.

Mania
The key symptom of bipolar disorder is elated mood. Hypomania is a happiness and zest for life in excess of that which is normal and is likely to be recognised by other people.

At this level, there may only be a limited degree of functional impairment. The increased sense of well-being and energy can actually make the person more active, although, for many people, the reduced need for sleep and increased activity can make this unsustainable.

As the severity of mood disturbance increases, the overactivity leads to multiple tasks being initiated but rarely done well or completed.

The patient may also have impaired concentration, be talkative, disinhibited and easily distracted.

In the DSM-IV1 the criteria for mania are met when the manic symptoms cause substantial impairment of occupational and social functioning and have lasted for seven days or more.

At this stage, psychotic symptoms may be present. Thought processes become speeded up (flight of ideas) and speech becomes very rapid.

The person may have delusions, which are typically mood congruent and grandiose. They may believe themselves to have special powers (for example, that they can fly). They may experience auditory hallucinations supporting these beliefs.

In DSM-IV, the term hypomania is restricted to episodes which last at least four days and include at least three manic symptoms.

This is clinically useful when subtyping bipolar disorder. In type 1, the person has had at least one manic episode and in type 2 at least one hypomanic episode (but no manic episode).

Depression
The symptoms of bipolar depressive episodes are essentially the same as in unipolar depressive disorder: low mood, loss of concentration, loss of energy and suicidal ideation.

Recent research suggests that patients with bipolar depression may tend to present with fewer typical features, such as insomnia and sadness, than those with unipolar depression.2

Mixed episodes
Sometimes mood is very variable, with rapid changes and/or both manic and depressive symptoms occurring.

Anxiety symptoms are often prominent, occurring in up to 80 per cent of patients. Patients with bipolar disorder are particularly at increased risk of cardiovascular disease, diabetes mellitus and thyroid disease.3

Other mental disorders, such as schizophrenia and substance abuse, should be considered. Medical disorders, such as hyperthyroidism, may present with elevated mood and hypercalcaemia with depressed mood. Apart from excluding other diagnoses, there is no diagnostic test for bipolar disorder.

Differential diagnosis
Bipolar disorder is often misdiagnosed. A common mistake is failure to ask about prior manic or hypomanic episodes in patients presenting with depressive episodes.

In our specialist clinic, we see a substantial number of patients who have presented with severe mania after being treated with antidepressant monotherapy. Therefore, it is important to consider the diagnosis in all patients presenting with clinically low mood.

Mania may be confused with schizophrenia when psychotic symptoms are present and it can be very difficult to differentiate between the two disorders purely on the basis of the clinical picture.

It is essential to obtain a history of the development of the disorder but even then there may be diagnostic uncertainty.

Particularly in younger patients with very variable mood, bipolar disorder may be misdiagnosed as emotionally unstable (borderline) personality disorder.

While there is some overlap in symptoms between the two disorders, the characteristic interpersonal difficulties are not a central feature of bipolar disorder. Adding to the complexity, the two disorders may co-exist.

NICE recommends that bipolar disorder should only be diagnosed if there is unequivocal evidence of mania.

Section 3: Managing the condition
Management is conventionally divided into acute (manic and depressive) and long term. Current developments emphasise the importance of facilitating self-management by psychoeducation, early symptom recognition and intervention in acute episodes.

Patients need rapid intervention (within hours or days) when they become ill. The GP, with responsive specialist back-up, is ideally placed to provide this model of care.

Treatment of mania and mixed episodes
Patients with manic symptoms that are not causing serious functional or behavioural disturbance and who retain insight can be successfully treated as outpatients. It is essential to start treatment early while the patient still has insight that they need treatment. More severe mania, especially if psychotic, will often require admission as this is the only way to guarantee treatment and avoid complications of the disease.

  • If patient is taking an antidepressant, it should be stopped.
  • Second generation (atypical) antipsychotics (SGAs) are highly effective and low doses may be used if given early (for example, risperidone 1mg or olanzapine 2.5mg). Adverse effects include sedation and weight gain. Risperidone and olanzapine are probably the most effective.
  • Lithium and valproate are also effective antimanics, although complex to use and less effective than SGAs.
  • Benzodiazepines are sometimes used but are not antimanic and SGAs should be preferred.
  • If the patient is taking lithium, the blood level should be checked and optimised (it also gives some indication of recent adherence).

Treatment of depressive episodes in bipolar disorder
Depressive episodes and symptoms in bipolar disorder can cause severe dysfunction and may be chronic and difficult to treat. The management of bipolar depression is now quite different from that of unipolar depression.

  • Optimise any mood stabiliser.
  • Use an SSRI plus antimanic. NICE recommends that antidepressants should be discontinued early.
  • Quetiapine 150-300mg.
  • Conventional antidepressants (particularly more potent drugs, such as venlafaxine and tricyclics) may worsen mood instability.

Prevention of relapse
Mood monitoring and diaries can help to prevent relapse. For example, the True Colours system allows remote mood monitoring by email and/or text message.

True Colours: allows remote mood monitoring by email or text

The patient receives a weekly email or text message and replies with the scores on a validated rating scale for both mania and depression. The scores over time are available to the patient and their clinicians.

As well as showing the total scores, the display can be annotated with events or changes in medication. It also shows the severity of symptoms - the more intense the colour the worse the manic or depressive symptoms. True Colours is available in some parts of the UK.

Long-term drug treatment
Long-term drug treatment should be offered if the patient has had at least two manic episodes, although it may be started after one serious episode, especially when there is a family history of bipolar disorder.

Lithium remains the standard therapy for bipolar disorder and reduces the risk of relapse by about 40-50 per cent (more effective against manic than depressive relapse) and also reduces the risk of suicide.4,5 NICE guidance for monitoring should be followed:

  • Serum lithium levels measured every three months.
  • Monitor older adults carefully for symptoms of lithium toxicity.
  • Monitor weight, especially in patients with rapid weight gain.
  • Perform thyroid and renal function tests every six months and more often if there is evidence of impaired renal function.

Other mood stabilisers
Valproate and olanzapine reduce the risk of manic relapse although the evidence base is less robust than lithium. Lamotrigine reduces the risk of depressive relapse. Other drugs, such as carbamazepine, may also be used although evidence is limited.

Psychological treatment
Family-focused therapy and psychoeducation can prevent relapse and help the patient to manage their own condition. The current evidence for cognitive behavioural therapy is conflicting.

Most psychological approaches share some common features including psychoeducation, problem-solving about community functioning and strategies to cope with mental illness stigma.

Other aspects of management
NICE recommends that people with bipolar disorder should have an annual physical health review, normally in primary care.

The check should include:

  • lipid levels, including cholesterol in all patients over 40 (because of high risk of cardiovascular disease)
  • glucose
  • weight
  • smoking and alcohol use
  • BP

Patients with bipolar disorder should be advised not to drive when acutely unwell and need to inform the DVLA of their disorder.

Section 4: Prognosis
Bipolar disorder runs a remitting and relapsing course in 90 per cent of patients. After one episode, the annual average risk of relapse is about 20 per cent. After more than three episodes, the annual average risk of relapse is about 40 per cent.

The prognosis is worse in young onset cases, rapid cycling bipolar disorder and women. Suicide and mortality rates are similar to depressive disorder.

Social problems
The disruption caused by the illness, especially the manic phases, often leads to problems maintaining relationships, employment and accommodation.

Over time, it is the depressive episodes rather than the manic episodes that cause most disability for most patients.

Section 5: Case study
Mrs RK is a 45-year-old married lady who first became manic at 35 following the death of her mother. Prior to this, she had suffered a number of depressive episodes starting at the age of 16, but had never been treated.

A friend described her personality as 'bubbly'. Following her mother's death, RK started to spend excessively, clean the house at night and had an extra-marital affair.

When she first presented, she was elated, irritable and talkative. She said that she felt better than she ever had before and refused treatment. She was eventually detained in hospital under the Mental Health Act and treated with olanzapine 15mg, making a good response over six weeks.

She was discharged and returned to work as a journalist but became depressed. The depression was difficult to treat and was maintained by the financial and relationship difficulties caused by the manic episode.

She was treated initially with fluoxetine 20mg but did not respond, so this was switched to venlafaxine increasing to 375mg daily. After six months her depression lifted but again her mood became elevated.

This was followed by a mixed episode in which her mood varied markedly during the day.

Lithium
The venlafaxine was stopped and olanzapine restarted. Her mood settled and she commenced lithium. She also commenced regular mood monitoring and was helped to identify early warning signs of manic and depressive episodes.

She read books, started to attend Manic Depression Fellowship groups and a self-management course and became an expert patient.

The lithium appeared to help attenuate the manic episodes but her recurrent low mood remained troublesome. Lamotrigine was added to the lithium and this helped reduce the severity of the low mood.

Mrs RK returned to full-time work and remained well, being seen annually in psychiatric outpatients and having lithium levels and physical health monitored regularly by her GP.

At her last appointment she was concerned that her 16-year-old daughter was beginning to display signs of mood instability and asked if there was a risk her daughter was developing bipolar disorder.

Section 6: Evidence base
Clinical trial

The bipolar affective disorder: lithium anticonvulsant comparative evaluation (BALANCE) trial compared lithium plus valproate with either drug alone in 330 patients with bipolar disorder type 1. Patients were recruited from 41 sites in UK, France and Italy.6

The risk of relapse was 40 per cent lower in patients allocated to combination therapy with lithium plus valproate than in those on valproate monotherapy.

Key text
The DSM-IV is produced by the American Psychiatric Association and provides criteria for the classification of mental disorders.

Curriculum
The RCGP covers this topic in statement 13 Care of People with Mental Health Problems. healthcarerepublic.com/curriculum

Online

  • Manic Depression Fellowship - The Bipolar Organisation www.mdf.org.uk

The website of the leading patient organisation focusing on bipolar disorder, previously known as the Manic Depression Fellowship.

The main patient information site of the NHS also includes links to Map of Medicine, which includes care pathways.

Guidelines

  • NICE. Bipolar disorder. CG38. 2006

This clinical guideline provides a comprehensive, evidence-based overview of the management of bipolar disorder. www.nice.org.uk

  • The British Association for Psychopharmacology guideline

This provides a comprehensive, up-to-date overview of general management and pharmacological treatment. www.bap.org.uk/pdfs/Bipolar_guidelines.pdf

References
1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders 2000. 4th ed, text revision. Washington, DC.

2. Perlis RH, Brown E, Baker RW et al.Clinical features of bipolar depression versus major depressive disorder in large multicenter trials. Am J Psychiatry 2006; 163(2): 225-31.

3. Kupfer DJ. The increasing medical burden in bipolar disorder. JAMA 2005; 293: 2528-30.

4. Geddes JR, Burgess S, Hawton K et al. Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials Am J Psychiatry 2004; 161(2): 217-22.

5. Cipriani A, Pretty H, Hawton K et al. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. Am J Psychiatry 2005; 162: 1805-19.

6. Geddes JR, Goodwin GM, Rendell J et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. Lancet 2010; 375 (9712): 385-95.

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Reflect on this article and add notes to your CPD Organiser on MIMS Learning

CPD IMPACT: Earn More Credits

These further impact points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Summarise this article and review the NICE guidelines on bipolar disorder, presenting the key points to your colleagues.
  • Write a practice protocol of how to manage patients who present acutely with psychosis.
  • Audit your prescribing of antidepressants, how often do you ask about features of rebound mania?

  • Contributed by Professor John Geddes, professor of epidemiological psychiatry at Warneford Hospital and the University of Oxford.

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