Ziprasidone Plus a Mood Stabilizer in Subjects With Bipolar I Disorder: A 6-Month, Randomized, Placebo-Controlled, Double-Blind Trial

Objective: To evaluate the efficacy and safety of ziprasidone adjunctive to a mood stabilizer for the maintenance treatment of bipolar mania. Method. Subjects with DSM-IV bipolar I disorder with a Mania Rating Scale score >= 14 were enrolled. Subjects achieving >= 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or valproate (period 1) were randomly assigned in the 6-month, double-blind maintenance period (period 2) to ziprasidone plus mood stabilizer or placebo plus mood stabilizer. The primary and key secondary end points were the time to intervention for a mood episode and time to discontinuation for any reason, respectively. Inferential analysis was performed using a Kaplan-Meier product-limit estimator (log-rank test). The study was conducted from December 2005 to May 2008. Results: A total of 127 and 113 subjects were randomly assigned to ziprasidone and placebo, respectively. Intervention for a mood episode was required in 19.7% and 32.4% of ziprasidone and placebo subjects, respectively. The time to intervention for a mood episode was significantly longer for ziprasidone than placebo (P = .0104). The median time to intervention for a mood episode among those requiring such an intervention (n = 61) was 43.0 days for ziprasidone versus 26.5 days for placebo. The time to discontinuation for any reason was significantly longer for ziprasidone (P = .0047). Adjunctive ziprasidone treatment was well tolerated. Among treatment-emergent adverse events occurring in >= 5% of subjects in either treatment group during period 2, only tremor occurred more frequently in the ziprasidone versus placebo group (6.3% vs 3.6%). Conclusions: Ziprasidone is an effective, safe, and well-tolerated adjunctive treatment with a mood stabilizer for long-term maintenance treatment of bipolar mania.