A randomized, double-blind, placebo-controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder

Objective: To investigate the safety and efficacy of aripiprazole in preventing relapse of a mood episode in recently manic- or mixed-episode patients with bipolar I disorder stabilized on aripiprazole. Method: This randomized, double-blind, parallel-group, placebo-controlled, multicenter study enrolled patients from 76 centers in 3 countries (Argentina, Mexico, United States) from March 2000 to June 2003. Bipolar I disorder (DSM-IV) patients who had recently been hospitalized and treated for a manic or mixed episode entered an open-label stabilization phase (aripiprazole monotherapy: 15 or 30 mg/day, 6-18 weeks). After meeting stabilization criteria (Young Mania Rating Scale score of! 10 and Montgomery-Asberg Depression Rating Scale score of <= 13 for 6 consecutive weeks), 161 patients were randomly assigned to aripiprazole or placebo for the 26-week, double-blind phase. The primary endpoint was time to relapse for a manic, mixed, or depressive episode (defined by discontinuation caused by lack of efficacy). Results: Aripiprazole was superior to placebo in delaying the time to relapse (p = .020). Aripiprazole-treated patients had significantly fewer relapses (25%) than placebo patients (43%; p = .013). Aripiprazole was superior to placebo in delaying the time to manic relapse (p = .01); however, no significant differences were observed in time to depressive relapse (p = .68). Weight gain ( >= 7% increase) occurred in 7 (13%) aripiprazole-treated and 0 placebo-treated patients. Adverse events ( >= 5% incidence and twice that of placebo) reported by aripiprazole-treated patients were akathisia, pain in the extremities, tremor, and vaginitis. Conclusions: Aripiprazole, 15 or 30 mg/day, was superior to placebo in maintaining efficacy in patients with bipolar I disorder with a recent manic or mixed episode who were stabilized and maintained on aripiprazole treatment for 6 weeks, as shown by a longer time to relapse.