To evaluate the efficacy, safety and tolerability of aripiprazole plus valproate/lithium in the treatment of patients with bipolar I mania partially non-responsive to lithium or valproate monotherapy.

This multicentre, randomized study included patients with bipolar I disorder (manic/mixed episode, with/without psychotic features). Partial non-responders with therapeutic lithium (0.6–1.0 mmol/l) or valproate (50–125 μg/ml) levels were randomized (2:1) to double-blind combination aripiprazole (aripiprazole [15–30 mg/day] + lithium/valproate; n=253) or placebo + lithium/valproate (n=131). The primary endpoint was mean change from baseline in YMRS Total Score at Week 6 (LOCF).

The aripiprazole combination therapy demonstrated significant improvement from baseline in the YMRS Total score versus placebo + lithium/valproate at Week 1 and all subsequent visits (all p<0.05) up to Week 6 (–13.3 vs. –10.7, p=0.002; LOCF). Significant improvements from baseline to Week 6 were observed with aripiprazole vs. placebo + lithium/valproate in CGI-BP-S (mania) score (–1.9 vs. –1.6; p=0.014; LOCF) and the LIFE-RIFT score (–1.76 vs. –0.99; p=0.046; LOCF). At endpoint, aripiprazole plus lithium/valproate was associated with significantly greater remission rate (YMRS Total score ≤12) and response rate (≥50% improvement from baseline in YMRS Total) than placebo + lithium/valproate. Similar percentages of patients had clinically relevant weight gain (aripiprazole + lithium/valproate vs. placebo + lithium/valproate: 3.0% vs. 3.9%; p=0.718, Week 6, LOCF). Aripiprazole combination therapy was well tolerated.

In patients with bipolar mania, aripiprazole in combination with lithium/valproate is an effective and well-tolerated treatment that improves psychosocial functioning.