SIGN clarifies the use of mood stabilisers in bipolar disorder

Bipolar affective disorder (manic depressive disorder) is relatively common, and many patients will be managed for most of their lives in the community. If they are to reach their full potential in life, it is important for the primary care team to be aware of the special needs and strengths of this group.

Prevalence of the disorder

With a lifetime prevalence of around 1.3%,^1,2 bipolar disorder is about as common as schizophrenia, but much less so than unipolar depression. The illness is episodic in nature, and patients may be severely incapacitated during their manic or depressive phase, yet function perfectly well between episodes, although some patients have subclinical symptoms or cognitive difficulties during these intervals. On the other hand, greater than average creativity can be found among both sufferers and their families.³

Difficulties with diagnosis

Because of the intermittent nature of symptoms, diagnosis of bipolar disorder can be difficult. Omitting the question about past episodes of increased activity, overspending or elation when interviewing depressed patients or their families may result in misdiagnosis.

Mania and hypomania are often confused: mania is the more severe version of the disorder; patients requiring admission to hospital are, by definition, manic. The American Psychiatric Association terminology distinguishes between bipolar I (illness with mania and often depression) and bipolar II disorder (illness with only hypomania and usually depression).²

Therapeutic options for bipolar illness

Treatment is complex and potentially tricky: unopposed antidepressant medication can trigger a manic episode, leading to the need for urgent intervention. Research into bipolar illness has traditionally been funded less generously than schizophrenia research. Because of this, and the difficulty of conducting long-term studies on this condition, the evidence base of well controlled studies is limited.

A number of expert-led reviews and guidelines for treatment are available,^4,5 and the Scottish Intercollegiate Guidelines Network (SIGN) has now published the first guideline on bipolar affective disorder based on SIGN methodology.⁶ For SIGN guidelines, a multidisciplinary development group of health professionals and patients uses an established format of systematic literature searching and evaluation, to demonstrate a direct link between evidence and clinical recommendations. ^6-8 To this end, studies and recommendations are graded according to the strength and applicability of the available evidence (Figure 1, below).⁶ The guideline is structured to reflect the natural history of bipolar disorder, being divided into treatment of mania and hypomania (Box 1, below), treatment of depressive episodes (Box 2, below) and long-term prophylactic treatment, both pharmacological and psychosocial (Box 3, below).⁶

Figure 1: Levels of evidence and grades of recommendation

Treatment of mania

Mania tends to be managed in hospital, while hypomania is treated in outpatient and community settings. In the UK, the traditional drug treatment for mania has been antipsychotic medication.

Some of the older antipsychotic drugs have been used as the gold standard to validate the effectiveness of the newer generation antipsychotics, so that results from a significant number of controlled trials are now available. There is also good evidence for the use of valproate (in its semisodium form) in acute mania.⁹

Lithium has the disadvantage that manic symptoms only respond after a delay, so that initial treatment with antipsychotics or valproate may be necessary.

Treatment of depression

Unopposed antidepressant treatment can trigger manic episodes. It is therefore recommended that antidepressants should be combined with antimanics (lithium, semisodium valproate or an antipsychotic).¹⁰

Prevention of relapse

Prevention of relapse in unipolar depression and schizophrenia relies mainly on continuation of acute treatments, but prophylaxis of manic and bipolar depressive episodes requires a fine balance of antimanic and antidepressant effects.

Evidence for these management strategies is very limited, owing to the complications involved in conducting randomised blind studies over at least 1 year, but there is good evidence for the efficacy of lithium salts in preventing mania and hypomania.¹¹ However, the narrow therapeutic dose range for lithium means that patients require regular review and blood testing.

Good practice suggests that local protocols for shared care should be implemented to minimise the risk of toxicity.⁶

The antimanic semisodium valproate is often used for prophylaxis, although there is good evidence only for its efficacy in acute episodes.¹² Carbamazepine is indicated for the prophylaxis of bipolar disorder if lithium is ineffective. In bipolar I, but probably not bipolar II, disorder lithium is more effective than carbamazepine.¹³

Some patients show poor concordance with oral medication, and sudden lithium withdrawal is associated with increased relapse rates. Intermittent use of medication can be responsible for the illness having a less stable course. For practical reasons, depot antipsychotic medication is occasionally used in such cases, sometimes in combination with antidepressant treatment.

Finally, one of the newer anticonvulsant drugs,lamotrigine,has been used off licence to prevent relapse of depression in bipolar illness.¹⁴

Psychosocial interventions to maintain symptom improvement

Psychotherapy for acute mania tends to be difficult and is generally avoided. Recommendations for the treatment of bipolar depression can only be made by extrapolating from evidence from depressed patients in general. For this reason, advice in the SIGN guideline is limited to psychotherapy for the maintenance of recovery in patients with bipolar affective disorder.⁶

A number of conceptual approaches have been used. Cognitive behavioural therapy assumes that thinking, mood and behaviour interact. Patients are taught techniques to monitor, examine and change their dysfunctional thinking and behaviour that is associated with undesirable mood states.¹⁵

Interpersonal and social rhythm therapy focuses on the impact of disrupted social rhythms, teaching patients to regularise their sleep-wake patterns, work, exercise, mealtimes and other daily activities, as well as addressing interpersonal problem areas.¹⁶

Behavioural family therapies for bipolar affective disorder have three main components: psycho-education, communication enhancement training and problem-solving skills training. They are designed to improve mood and family functioning, and reduce risk of relapse.¹⁷

Interestingly, there are areas of overlap between different interventions: both interpersonal and social rhythm therapy and cognitive behavioural therapy focus on the detection of early warning signs of relapse. Psycho-educational approaches generally emphasise compliance with medication, detecting early signs and seeking help.¹⁸

Managing the risk of suicide

A significant risk in bipolar affective disorder is that of suicide during a depressive or mixed (e.g. depressed mood rapidly followed by playful overactivity) affective episode. Controlled studies suggest that lithium treatment reduces the risk of suicide in these patients.¹⁹ This is one of the very few instances of evidence for the efficacy of a medical intervention in reducing suicide risk (although it should be noted that these studies were not randomised). Optimising treatment with lithium by enhancing compliance and minimising side-effects is clearly indicated. It cannot be excluded that the protective effect of lithium on suicide risk may be non-specific, i.e. related to the increased support and supervision that these patients receive.

Pregnant patients

GPs have an important role in preconception counselling of patients with bipolar disorder.⁶ As well as general problems, such as smoking and alcohol use, nutrition, rubella, HIV and hepatitis B status, there are potential problems which are more specific to bipolar affective disorder (Box 4, below). Depending on the circumstances, the GP may want to work in a shared care arrangement with a specialist psychiatrist or obstetrician.

Conclusion

The management of patients with bipolar affective disorder, particularly on lithium, is a major challenge to clinical and organisational skills. Usually a computerised register and a recall system are required to prevent the gradual development of toxicity and to maximise treatment compliance. The effort is worthwhile, however, because there is good evidence that patients on lithium (or attending a lithium clinic, which is often the same thing) have reduced suicide rates.

Collaboration with other professionals e.g. psychologists or community psychiatric nurses, who may offer one of the psychotherapies that enhance early symptom recognition and compliance with medication, is often helpful.

Increasingly, patient groups such as the Manic Depression Fellowship (www.mdf.org.uk/) are available to advise and provide feedback on healthcare issues. Professionals should make full use of such resources. The guideline contains a list of sources of further information and support for patients and carers.

SIGN Guideline 82. Bipolar affective disorder can be downloaded from the SIGN website: www.sign.ac.uk

Reference

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