To evaluate the efficacy and safety of aripiprazole monotherapy as acute and continuation therapy for acute bipolar I mania.

Patients with acute bipolar I mania were randomized (1:1:1) to double-blind aripiprazole (15–30 mg/day; n=155), placebo (n=165) or lithium (900–1500 mg/day; n=160) for 3 weeks. At the end of Week 3, patients randomized to placebo were blindly switched to aripiprazole. Key efficacy outcome measures were mean change from baseline in YMRS Total score at Week 3 (LOCF; primary endpoint) and Week 12.

Improvements in YMRS Total scores from baseline were significantly greater versus placebo as early as Day 2 with aripiprazole (p=0.003) and Day 7 with lithium (p=0.040; LOCF). At Week 3, improvements from baseline in mean YMRS Total scores were significantly greater with aripiprazole (–12.96; p<0.001) and lithium (–12.03; p=0.005) versus placebo (–9.01; LOCF). These improvements were maintained to Week 12 (LOCF) with both aripiprazole (–14.48) and lithium (–12.71). Response rate was significantly greater versus placebo as early as Day 2 with aripiprazole (p=0.026), and Day 10 with lithium (p=0.006; LOCF). Response rates continued to increase over the study period and at Week 12 were 56.5% with aripiprazole and 49.0% with lithium.

Aripiprazole significantly improved symptoms as early as Day 2 and throughout the 3-week, placebo-controlled portion of this study in acutely manic patients. The beneficial effects of aripiprazole were sustained through Week 12 and were similar to lithium, confirming the robust efficacy of aripiprazole in these patients.