Background: Bipolar disorder is a chronic, recurrent disorder with a significant negative impact on quality of life. Effective treatments are available for acute mania. In contrast, there is a lack of consensus on the treatment of acute bipolar depression and long treatment options for bipolar disorder require more study. Aripiprazole is FDA approved for the treatment of acute mania. This paper reviews current data on the efficacy of aripiprazole in the treatment of acute bipolar depression and in maintenance therapy of bipolar disorder.
Methods: PubMed and abstracts of recent conferences were searched for randomized, double-blind studies that investigated the efficacy of aripiprazole in acute bipolar depression or maintenance therapy of bipolar disorder.
Results: Two studies assessed the efficacy of aripiprazole monotherapy in the treatment of acute bipolar depression. These showed that although aripiprazole significantly reduced depressive symptoms early in treatment, the results were not significantly different from placebo at the primary end point of week 8. As to long-term treatment, aripiprazole was superior to placebo in delaying time to relapse for manic episodes, but not for depressive episodes after 26 and 100 weeks of maintenance therapy. Aripiprazole was as effective as lithium, and adjunctive aripiprazole with lithium or valproate was more effective than placebo plus lithium or valproate, in preventing a manic relapse. Reductions in manic and mixed relapse rates compared to placebo were achieved in a study combining aripiprazole with lamotrigine; however, the results were not statistically significant. Similar to other maintenance studies, depressive relapse rates were not significantly reduced compared to placebo.
Limitations: Negative findings for aripiprazole in the treatment of acute bipolar depression have been attributed to high study doses, rapid titration, and high placebo rates. A recent post-hoc analysis demonstrated that aripiprazole was more effective in patients with severe depressive symptoms, particularly for patients on a lower dose. Further research is needed to confirm this finding. The inability of aripiprazole to reduce the time to depressive relapse during maintenance therapy may be due to the recruitment of patients with an index manic episode and a consequent lower incidence of depressive relapses. Therefore, studies using a depression index episode are needed to appropriately evaluate relapse prevention.
Conclusions: Although aripiprazole has proven efficacy for acute mania and the prevention of mania, the evidence available thus far does not support the efficacy of aripiprazole for the treatment of acute bipolar depression and prevention of depressive relapse. Further studies with appropriate doses and a depressive index episode are needed to clarify the role of aripiprazole in bipolar disorder.
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