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Preventing Relapse in Bipolar Disorder

Content provided by the Faculty of the Harvard Medical School

An international study has concluded that lithium alone, or the combination of lithium and valproate (Depakote), is more effective than valproate alone in preventing relapse in patients with bipolar disorder. At the same time, however, the study provides a reminder that relapse is common in such patients, even when they take medication regularly.

Investigators launched the Bipolar Affective Disorder: Lithium/Anticonvulsant Evaluation (BALANCE) trial in part because prescription patterns have changed so dramatically since 2000. Lithium was once the only option available to patients with bipolar disorder, and is still considered the best agent for reducing risk of suicide. Although effective, lithium can damage the kidneys. When lithium levels in a patient's blood exceed a narrow therapeutic window, this drug can also have other toxic effects.

Current practice guidelines recommend valproate as an alternative first-line treatment for long-term maintenance therapy. Partly as a result, prescription patterns have changed. In the United States, for example, lithium prescriptions dropped by about 40% in the 1990s, while valproate prescriptions rose by 250%.

The BALANCE trial enrolled patients with bipolar disorder, ages 16 and older, in the United States, United Kingdom, France, and Italy. Investigators randomly assigned 330 patients to lithium alone, valproate alone, or combination treatment. This was an open-label study, which meant that both the researchers and participants knew which drug a patient was taking during the trial. Participants were then followed for up to two years, with relapse determined by the need for a greater dosage, a different drug, or hospitalization.

At the 24-month mark, 54% of participants who took both lithium and valproate had relapsed, compared with 59% of participants who took lithium alone and 69% of participants who took valproate alone. The difference in relapse rates was statistically significant — and worse — only for valproate alone. Combination treatment appeared most effective in preventing manic episodes, while lithium alone was better at preventing depressive episodes.

The study had several limitations, notably the absence of a placebo treatment and a structured assessment of symptoms. But given the results, the authors recommended that clinicians consider advising patients that they might have a better outcome by taking lithium, alone or in combination with valproate.

Geddes JR, et al. "Lithium Plus Valproate Combination Therapy versus Monotherapy for Relapse Prevention in Bipolar I Disorder (BALANCE): A Randomized Open-Label Trial," The Lancet (Jan. 30, 2010): Vol. 375, No. 9712, pp. 385–95.

Last Annual Review Date: 2010-05-01T00:00:00-06:00 Copyright: © Harvard Health Publications

Reference: Bipolar Disorder section on Better Medicine


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