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CNS Drugs

, Volume 20, Issue 1, pp 29–42 | Cite as

Polytherapy in Bipolar Disorder

  • Daniel Lin
  • Hiram Mok
  • Lakshmi N. Yatham
Therapy In Practice

Abstract

Bipolar disorder is a life-long condition that is associated with frequent recurrence/relapse of symptoms. Although putative mood stabilisers, such as lithium, are considered to improve the natural course of bipolar disorder, complete long-term remission is rarely achieved. In order to effectively control mood symptoms and to reduce relapse, clinicians often use polypharmacy to treat patients with bipolar disorder. In this article, we examine the recent literature on treatment strategies in bipolar disorder to determine if combination treatments provide additional benefit over monotherapy for the management of various phases of bipolar disorder.

The evidence suggests that for acute mania a combination of lithium or valproate and an atypical antipsychotic is the most effective approach, with approximately 20% more patients responding to the combination than to monotherapy with any antimanic agent. Few studies have examined the use of combination therapy in comparison to monotherapy for bipolar depression. The limited evidence suggests that lithium plus an antidepressant appears to be more effective than lithium alone in those with lower serum lithium concentrations. Similarly, the combination of olanzapine plus fluoxetine is more effective than olanzapine alone. There is consensus that antidepressant monotherapy is not appropriate because of concerns of a manic switch, but monotherapy with lithium or lamotrigine may be adequate for mild to moderate bipolar depression.

For maintenance treatment, commonly used agents, such as lithium, valproate or olanzapine appear to be most effective in preventing manic relapses, whereas lamotrigine is more effective in preventing depressive relapses. As a result of these findings, it makes intuitive sense to combine lamotrigine with lithium, valproate or an atypical antipsychotic to achieve better mood stability. However, the efficacy and safety of such combinations have not been systematically compared with monotherapy. Preliminary studies suggest that lithium plus valproate may be more effective than lithium alone in preventing affective relapses. Similarly, the combination of lithium or valproate plus olanzapine seems to be more effective than monotherapy with a mood stabiliser in preventing manic episodes.

Keywords

Bipolar Disorder Carbamazepine Risperidone Olanzapine Paroxetine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Dr Yatham has been a consultant/speaker and received grant funding from Eli Lilly, AstraZeneca, Janssen, Bristol Myers Squibb, and GlaxoSmithKline. Dr Mok has been a consultant and speaker for Lundbeck, Wyeth, Eli Lilly, Janssen and AstraZeneca. No sources of funding were used to assist in the preparation of this review.

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© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.Department of PsychiatryUniversity of British ColumbiaVancouverCanada
  2. 2.Department of Psychiatry, Mood Disorders CentreUniversity of British ColumbiaVancouverCanada

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