Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: A 100-week, double-blind study versus placebo

Objective: A 26-week, double-blind, placebo-controlled relapse prevention study of aripiprazole was designed a priori with a prospective, 74-week, double-blind, placebo-controlled extension phase. Efficacy and tolerability of aripiprazole for relapse prevention in bipolar I disorder was, therefore, evaluated for 100 weeks. Method: Patients with DSM-IV bipolar I disorder, recent manic or mixed episode, received open-label aripiprazole 15 or 30 mg/day (started at 30 mg/day) for 6 to 18 weeks. Patients achieving stabilization (Young Mania Rating Scale score <= 10 and Montgomery-Asberg Depression Rating Scale score <= 13 for 6 consecutive weeks) entered the double-blind phase, at which point they were randomly assigned to double-blind treatment with aripiprazole or placebo for 26 weeks. The primary endpoint was time to relapse for any mood episode. Patients who completed the 26-week stabilization continued in a double-blind fashion with aripiprazole or placebo for an additional 74 weeks and were monitored for relapse, efficacy, and tolerability. The study was conducted from March 2000 to June 2003. Results: In total, 161 patients met the stabilization criteria and were randomly assigned to aripiprazole (N = 78) or placebo (N = 83). At 100 weeks, time to relapse was significantly longer with aripiprazole (N = 7) than placebo (N = 5; hazard ratio = 0.53 [p =.011; 95% CI = 0.32 to 0.87]); however, a further 24 patients had discontinued due to study closure. Aripiprazole was superior to placebo in delaying time to manic relapse (p =.005; hazard ratio = 0.35 [95% CI = 0. 16 to 0.75]); however, no significant differences were observed in time to depressive relapse (p =.602; hazard ratio = 0.81 [95% CI= 0.36 to 1.81]). The adverse events reported during 100 weeks of treatment with aripiprazole versus placebo (>= 5% incidence and twice placebo rate) were tremor, akathisia, dry mouth, hypertension, weight gain, vaginitis, abnormal thinking, pharyngitis, and flu syndrome. Mean weight change from baseline to 100 weeks (last observation carried forward) was +0.4 +/- 0.8 kg with aripiprazole and -1.9 +/- 0.8 kg with placebo. Conclusions: Over a 100-week treatment period, aripiprazole monotherapy was effective for relapse prevention in patients who were initially stabilized on aripiprazole for 6 consecutive weeks, and it maintained a good safety and tolerability profile.