Ziprasidone HCl capsules for the adjunctive maintenance treatment of bipolar disorder in adults.

This article reviews the evidence for the use of ziprasidone for the maintenance treatment of bipolar I disorder in adults as an adjunct to lithium or valproate, as approved by the US FDA in 2009. Ziprasidone is an 'atypical' or 'second-generation' antipsychotic that has garnered clinical interest because of its metabolically friendly tolerability profile. A placebo-controlled trial was conducted in subjects whose most recent episode was manic or mixed, with or without psychotic features, and with symptoms that began no more than 90 days prior to the screening visit. Patients were stabilized during a 10-16-week, open-label period on the combination of ziprasidone 80-160 mg/day plus lithium (0.6-1.2 mEq/l) or valproate (50-125 microg/ml). Patients whose symptoms stabilized for 8 consecutive weeks were randomized to either continue combination treatment with adjunctive ziprasidone or receive lithium or valproate with adjunctive placebo for up to 24 weeks of double-blind treatment. The primary outcome measure was time to intervention for a mood episode during the double-blind period, tested statistically using survival analysis and assessing Kaplan-Meier curves. Of the 584 patients enrolled in the open-label period, 241 (41%) completed. A total of 238 subjects were analyzed for efficacy in the double-blind period (ziprasidone 127, placebo 111). Ziprasidone was superior to placebo in increasing the time to recurrence of a mood episode (p = 0.0104) during the 6 months of double-blind treatment. Only 19.7% (25 out of 127) of the ziprasidone subjects required intervention for a mood episode, compared with 32.4% (36 out of 111) of the placebo subjects (number needed to treat [NNT] 8; 95% CI: 5-62). The most robust effects were noted for the combination of ziprasidone and lithium and for the avoidance of manic/mixed episodes. Ziprasidone had no remarkable effect on weight or blood glucose. Limitations of this study include the enriched sample and exclusion of the most severely ill, and the inclusion of only those patients whose most recent bipolar episode was manic or mixed. Indirect comparisons of adjunctive ziprasidone with adjunctive quetiapine reveals a lower (i.e., more robust) NNT for quetiapine in terms of proportions of subjects experiencing a mood event (NNT: 4), but a higher incidence of bodyweight gain of at least 7% from baseline.