The role of ziprasidone in adjunctive use with lithium or valproate in maintenance treatment of bipolar disorder

OBJECTIVES: This article addresses the clinical role for ziprasidone used adjunctively with a mood stabilizer in maintenance treatment of bipolar disorder. This review also addresses the strengths and limitations of design features in adjunctive studies of second-generation antipsychotic drugs added to mood stabilizers. METHODS: The principal study relevant to this review enrolled subjects who were ≥18 years of age, experiencing a recent or current manic or mixed bipolar I episode, with at least moderately severe current manic symptoms. To meet criteria for randomization to 6 months maintenance treatment, patients had to have failed a short course of treatment with either lithium or valproate and achieved benefit with added ziprasidone for 8 consecutive weeks. RESULTS: Time to intervention for a new mood episode as well as time to discontinuation for any reason was significantly longer with adjunctive ziprasidone treatment than with monotherapy treatment with mood stabilizer. Three dosages of ziprasidone augmentation were studied. Patients treated with 120 mg/day had better efficacy and overall outcomes than did patients who received 80 or 160 mg/day of ziprasidone. CONCLUSIONS: Good evidence exists that adjunctive ziprasidone will likely provide greater overall efficacy coupled with good tolerability for at least a 6-month period than a strategy of continued monotherapy with a mood stabilizer. Changes in open phases of maintenance studies to reduce study enrichment, in study endpoints, and in statistical approaches to analysis of data are warranted.