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Abstract
Acute manic episodes in bipolar disorder require rapid and effective relief. Bipolar depression is a major component of the bipolar disorder spectrum. Existing treatment options for bipolar depression include lithium, lamotrigine and conventional antidepressants. However, lithium is more effective in treating mania or hypomania than depression, both acutely and prophylactically, lamotrigine has only been demonstrated to be effective in one adequately powered study in acute bipolar I depression, and conventional antidepressants have been associated with emergent mania and cycle acceleration. Symptomatic outpatients can expect to spend, on average, 33% of their time in the depressive phase compared with 11% in the manic phase. Consequently, there is a need for additional agents to effectively treat bipolar depression. The atypical agents olanzapine, risperidone and quetiapine have demonstrated efficacy against the manic phase of bipolar disorder and appear also to have potential in the depressive phase. Olanzapine monotherapy significantly improved depressive symptoms compared with placebo in patients with bipolar disorder in an 8-week randomized, controlled clinical study, but the magnitude of the clinical effect was small. The observed improvement in depressive symptoms became moderately large when olanzapine was combined with the antidepressant fluoxetine. Quetiapine monotherapy also resulted in significant improvements compared with placebo in patients with either bipolar I or bipolar II disorder in another 8-week randomized, controlled clinical study, but the effect size was large. A 6-month open-label study of risperidone added to ongoing therapy demonstrated improvements in depressive symptoms in patients with bipolar and schizoaffective disorders experiencing a manic, hypomanic, mixed or depressive episode. The receptor-binding profile of these agents supports a role in the treatment of depressive symptoms and clinical data are beginning to emerge of their efficacy in both the acute and maintenance setting.