Reevaluating therapies for bipolar depression.

The most commonly employed pharmacotherapies for bipolar depression include antidepressants, lithium, and anticonvulsants, such as lamotrigine, valproate, and carbamazepine. A combination of these agents, usually an antidepressant and a mood stabilizer, is often required to achieve an optimal response. However, some treatment guidelines still caution that antidepressant exposure should be minimized in patients with bipolar depression, due to concern that they may trigger treatment-emergent mania or cycle acceleration. This advice prevails despite data showing that antidepressants are effective in treating bipolar depression and evidence that coadministration of a mood-stabilizing medication, 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 mood stabilizer monotherapy. Although the antidepressant efficacy of most mood stabilizers has not been satisfactorily proven, first-line therapy with 1 mood stabilizer alone or a combination of 2 mood stabilizers is still recommended by many guidelines. Inappropriate treatment of bipolar depression may leave 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 depression both as monotherapy and when combined with a mood stabilizer should be studied in adequately powered trials in order to revise treatment guidelines. Electroconvulsive therapy remains an option for treatment-refractory patients and those intolerant to pharmacologic treatment, as well as patients who are pregnant or at high risk of suicide.