Abstract

For the majority of patients with bipolar disorder, major depressive episodes represent the most debilitating and difficult-to-treat illness dimension. Patients spend significantly more time depressed than manic or hypomanic, and attempt suicide more frequently during this illness phase, yet the availability of treatments remains limited. The discovery of more effective therapeutics for managing depressive episodes is arguably the greatest unmet need in bipolar disorder. This article provides an evidence-based summary of pharmacological treatments for the acute and longitudinal management of bipolar depression. Clinical trial results are reviewed for a diverse array of compounds, inclusive of traditional mood stabilizers (eg, lithium and divalproex), atypical antipsychotics, unimodal antidepressants, and modafinil. Where applicable, differences in efficacy across compounds are examined through discussion of number needed to treat and effect size determinations. A pragmatic clinical approach is presented for management of the depressed phase of bipolar disorder.

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