OBJECTIVE: Several lines of research suggested that aripiprazole might be a useful treatment for acute bipolar depression. The aim of this open-label trial is to give more evidence of the clinical effectiveness and tolerability of aripiprazole in acute bipolar depression. RESEARCH DESIGN AND METHODS: Aripiprazole response was prospectively assessed for 16 weeks using the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Severity Scale (CGI-S), and the Young Mania Rating Scale in 85 bipolar patients with acute depression inadequately responsive to one mood stabilizer. MAIN OUTCOME MEASURES: Aripiprazole was well tolerated. Only three (3.5%) patients discontinued the study for side effects. The most common side effect was akathisia, occurring in 17/80 (21.2%) patients. Patients showed statistically insignificant weight gain (0.9 +/- 2.64 kg) over the 16-week trial. RESULTS: Patients showed a significant decrease in mean MADRS and CGI-S, and 80 (94.1%) patients completed the 16-week trial. Thirty-nine (45.8%) patients received aripiprazole as monotherapy and 46 received the drug adjunctively (54.1%). Fifty-two (65%) patients met criteria for response (>/= 50% reduction in MADRS total score), 30 (37.5%) patients met criteria for remission (final MADRS total score </= 12). CONCLUSIONS: Aripiprazole was associated with beneficial effects on mood in patients with bipolar depression, and appears well tolerated with very small changes in mean body weight. These results highlight the potential benefits of aripiprazole for bipolar disorder patients. However, double-blind, placebo-controlled studies are necessary to confirm aripiprazole's efficacy, tolerability and safety in bipolar depression.