Aripiprazole plus divalproex for recently manic or mixed patients with bipolar I disorder: a 6-month, randomized, placebo-controlled, double-blind maintenance trial.

Objectives: The goal of this study was to investigate the safety and efficacy in preventing relapse of a mood episode in recently manic or mixed episode patients with bipolar I disorder stabilized with aripiprazole and divalproex combination.

Methods: This randomized, 24-week, double-blind, placebo-controlled multicenter study enrolled patients from 23 centers in Korea. Patients with bipolar I disorder who had manic or mixed episode entered a 6-week open-label stabilization phase. After meeting stabilization criteria, 83 patients were randomly assigned to placebo + divalproex or aripiprazole + divalproex treatment group for the 24-week, double-blind maintenance phase.

Results: During the 6-month double-blind treatment, the time to relapse of any mood episode in the aripiprazole group was longer than the placebo group, but the difference did not reach statistical significance (p = 0.098). After controlling for mean divalproex level, the time to depressive episode relapse in the aripiprazole group was longer than those in the placebo group (p = 0.029). Weight gain (≥ 7% increase) occurred in 22.5% aripiprazole group and 18.6% placebo group (p = 0.787).

Conclusions: In this study, relapse of mood episode occurred fewer and later for aripiprazole with divalproex treatment than divalproex monotherapy, but the differences were not statistically significant.