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Reevaluating Therapies for Bipolar Depression

Heinz Grunze, MD, PhD

Published: June 15, 2005

Article Abstract

The most commonly employed pharmacotherapies for bipolar depression include antidepressants,lithium, and anticonvulsants, such as lamotrigine, valproate, and carbamazepine. A combinationof these agents, usually an antidepressant and a mood stabilizer, is often required to achieve an optimalresponse. However, some treatment guidelines still caution that antidepressant exposure shouldbe minimized in patients with bipolar depression, due to concern that they may trigger treatment-emergentmania or cycle acceleration. This advice prevails despite data showing that antidepressantsare effective in treating bipolar depression and evidence that coadministration of a mood-stabilizingmedication, at least with modern antidepressants, such as the selective serotonin reuptake inhibitors,can reduce the risk of treatment-emergent mania to levels comparable with those observed with moodstabilizer monotherapy. Although the antidepressant efficacy of most mood stabilizers has not beensatisfactorily proven, first-line therapy with 1 mood stabilizer alone or a combination of 2 mood stabilizersis still recommended by many guidelines. Inappropriate treatment of bipolar depression mayleave patients at high risk of suicide and increased chronicity of symptoms; effective therapy should,therefore, be provided as early as possible. The efficacy and safety of antidepressants for bipolar depressionboth as monotherapy and when combined with a mood stabilizer should be studied in adequatelypowered trials in order to revise treatment guidelines. Electroconvulsive therapy remains anoption for treatment-refractory patients and those intolerant to pharmacologic treatment, as well aspatients who are pregnant or at high risk of suicide.

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