Evidence-based guidance should improve the shared care management of bipolar affective disorder in the community, says Professor Klaus Ebmeier

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
Box 1: Recommendations for the treatment of acute mania, with grades
  • Acute manic episodes should be treated with oral administration of an antipsychotic drug or semisodium valproate (A)
  • Lithium can be used if immediate control of overactive or dangerous behaviour is not needed or otherwise should be used in combination with an antipsychotic (A)
  • Intramuscular injection of antipsychotics and/or benzodiazepines (lorazepam), should be used in emergency situations, in accordance with local protocols (GPP)
  • Benzodiazepines may be used as adjunctive treatment in acute mania where sedation is a priority (GPP)
  • Patients who suffer an acute manic episode whilst on maintenance treatment with an antimanic drug should have their dose of antimanic drug optimised. Treatment with an antipsychotic or valproic acid should be initiated as appropriate (GPP)
  • Severe, treatment-resistant mania may require electroconvulsive treatment (ECT) to avert harm due to the illness (GPP)
  • Combination therapy with several antimanic agents from different classes may be required in treatment resistant cases (GPP)
  • Duration of treatment will be determined by the reduction of symptoms, the emergence of side-effects and the need to provide treatment for residual symptoms and prevent relapse (see section 4) (GPP)
  • Antidepressant drug treatment should be reduced and discontinued during an acute manic episode (see section 3.2.1) (GPP)
  • A clear terminology should be implemented to avoid confusion in the prescription of sodium valproate and semisodium valproate, as well as the different lithium salts and preparations (GPP)
Box 2: Recommendations for the treatment of acute depression, with grades
  • An antidepressant in combination with an antimanic drug (lithium, semisodium valproate or an antipsychotic drug), or lamotrigine is recommended for the treatment of acute bipolar depression in patients with a history of mania (B)
  • Patients maintained on mood stabilisers who suffer a depressive episode should be started on an antidepressant after optimising their mood stabiliser (GPP)
  • Interactions between serotonergic antidepressants, antipsychotic drugs and lithium and the risk of triggering mania or rapid cycling should be considered when selecting an antidepressant (GPP)
  • ECT should be considered for patients with bipolar depression who are at high risk of suicide or self-harm (GPP)
Box 3: Strategies for prevention of relapses, with grades
Pharmacological relapse prevention
  • Lithium is the treatment of choice for relapse prevention in bipolar affective illness (A)
  • Lithium should be prescribed at an appropriate dose with a daily dosing regimen (A)
  • The withdrawal of lithium should be gradual to minimise the risk of relapse (A)
  • In general practice, lithium should be prescribed in the context of a shared care protocol to minimise side-effects and toxicity (GPP)
  • Before embarking on maintenance treatment with lithium, patient and doctor should consider severity of the last episode, number, frequency and severity of previous episodes, personal factors, such as a wish to become pregnant or the wish to avoid sick leave from work or education. Patient concordance and ability to take regular medication will be essential for some treatments (lithium), but not for others (depot antipsychotic medication) (GPP)
  • Carbamazepine can be used as an alternative to lithium, particularly in patients with bipolar II, or when lithium is ineffective or unacceptable (A)
  • Lamotrigine can be used for prophylaxis in patients who have initially stabilised with lamotrigine, particularly if depressive relapse is a greater problem than manic relapse (A)
  • Re-establishing prophylactic treatment should be considered after delivery in women who have discontinued treatment during pregnancy (GPP)
Psychosocial interventions
  •  

    Evidence-based psychosocial interventions should be available to patients in addition to pharmacological maintenance treatment, especially if complete or continued remission cannot be achieved (B)
Suicide prevention
  •  

    Acute and maintenance lithium treatment of patients with bipolar affective disorders should be optimised to make every effort to minimise the risk of suicide (D)

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.

Box 4: Potential problems to be considered in pregnant patients with bipolar affective disorder
  • The effects of the disorder on the pregnancy, such as the effects on physical health associated with depression
  • The effects of drugs used to treat bipolar disorder, especially lithium and anticonvulsant drugs. Most of the drugs used for long-term treatment are potentially teratogenic.The SIGN guideline makes recommendations for the use of lithium, valproate and carbamazepine during pregnancy and breastfeeding
  • The use of folic acid to prevent neural tube defects
  • Monitoring of the illness: this may need to be increased to provide additional reassurance to the patient and also to detect early relapse
  • Relapse during pregnancy, which is more likely if lithium is discontinued
  • Postnatal relapse: if lithium is stopped, there is an eightfold increase in hospital admission rates in the first month postpartum, and a twofold increase in admission rates between months 2 and 12 20
  • The risk of the child suffering from bipolar disorder in later life
  • Postnatal issues including breastfeeding, postnatal withdrawal from psychotropic drugs and potential long-term consequences6

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

  1. Weissman MM, Bland RC, Canino GJ et al. Crossnational epidemiology of major depression and bipolar disorder. JAMA 1996; 276: 293-9.
  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edition. Washington, DC: American Psychiatric Association, 1994.
  3. Jamison KR.Touched with fire: manic-depressive illness and the artistic temperament. New York: Free Press, 1994.
  4. American Psychiatric Association. Practice guidelines for the treatment of psychiatric disorders compendium 2002. Washington: American Psychiatric Association, 2002.
  5. Goodwin GM,Young AH.The British Association for Psychopharmacology guidelines for treatment of bipolar disorder: a summary. J Psychopharmacol 2003;17(4 Suppl): 3-6.
  6. Scottish Intercollegiate Guidelines Network. SIGN 82. Bipolar affective disorder. Edinburgh: SIGN, 2005.
  7. Scottish Intercollegiate Guidelines Network. SIGN 50. A guideline developerís handbook (revised and updated). Edinburgh: SIGN, 2004.
  8. National Institute for Clinical Excellence (NICE) Scottish Intercollegiate Guidelines Network (SIGN) Comparison of methodologies. www.sign.ac.uk/methodology/comparison.html.
  9. Macritchie K, Geddes JR, Scott J et al.Valproate for acute mood episodes in bipolar disorder (Cochrane Review). In: The Cochrane Library, Issue 2. Chichester, UK: John Wiley & Sons, 2004.
  10. Gijsman HJ, Geddes JR, Rendell JM et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 2004; 161: 1537-47.
  11. 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: 217- 22.
  12. Bowden CL, Calabrese JR, McElroy SL et al. A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Arch Gen Psychiatry 2000; 57: 481-9.
  13. Greil W, Kleindienst N. The comparative prophylactic efficacy of lithium and carbamazepine in patients with bipolar I disorder. Int Clin Psychopharmacol 1999; 14: 277-81.
  14. Calabrese JR, Bowden CL, Sachs G et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry 2003; 64: 1013-24.
  15. Lam DH, Watkins ER, Hayward P et al. A randomized controlled study of cognitive therapy for relapse prevention for bipolar affective disorder: outcome of the first year. Arch Gen Psychiatry 2003; 60: 145-52.
  16. Frank E, Hlastala S, Ritenour A et al. Inducing lifestyle regularity in recovering bipolar disorder patients: results from the maintenance therapies in bipolar disorder protocol. Biol Psychiatry 1997; 41: 1165-73.
  17. Miklowitz DJ, George EL, Richards JA et al. A randomized study of family-focused psychoeducation and pharmacotherapy in the outpatient management of bipolar disorder. Arch Gen Psychiatry 2003; 60: 904-12.
  18. Gonzalez-Pinto A, Gonzalez C, Enjuto S et al. Psychoeducation and cognitive-behavioral therapy in bipolar disorder: an update. Acta Psychiatr Scand 2004; 109: 83-90.
  19. Tondo L, Hennen J, Baldessarini RJ. Lower suicide risk with long-term lithium treatment in major affective illness: a meta-analysis. Acta Psychiatr Scand 2001; 104: 163-72.
  20. Altshuler LL, Cohen L, Szuba MP et al. Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines. Am J Psychiatry 1996; 153: 592-606.

Guidelines in Practice, August 2005, Volume 8(8)
© 2005MGP Ltd
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