Amisulpride plus valproate vs haloperidol plus valproate in the treatment of acute mania of bipolar I patients: a multicenter, open-label, randomized, comparative trial.

The primary objective of this study was to compare the effectiveness of combination treatment of valproate and amisulpride with that of valproate and haloperidol in bipolar I disorder. Adult inpatients with a current manic episode fulfilling DSM-IV-TR diagnostic criteria for bipolar type I disorder were included. Patients were randomized to amisulpride (400-800 mg/day) or haloperidol (5-15 mg/day) for 3 months and all received valproate. The primary effectiveness criterion was the percentage of responders (defined by a decrease of >/=50% of the Y-MRS) in patients completing the study. Safety was evaluated by adverse event reporting, determination of extrapyramidal function and clinical examination. Sixty-two patients were randomized to receive valproate-amisulpride, and 61 to receive valproate-haloperidol. At study end, responder rates were 72.6% in the amisulpride group and 65.5% in the haloperidol group. Remission rates were 83.9% and 89.7%, respectively. At study end, neither response rates nor remission rates differed significantly between groups. Treatment-emergent adverse events occurred significantly (p = 0.009) more frequently in the haloperidol group (86.4%) than in the amisulpride group (66.1%). In conclusion, the valproate-amisulpride combination was as effective as the valproate - haloperidol combination in bipolar I patients, with a better safety profile.