Ziprasidone plus a mood stabilizer in subjects with bipolar I disorder: a 6-month, randomized, placebo-controlled, double-blind trial

J Clin Psychiatry. 2010 Feb;71(2):130-7. doi: 10.4088/JCP.09m05482yel. Epub 2010 Jan 26.

Abstract

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 > or = 14 were enrolled. Subjects achieving > or = 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 > or = 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.

Trial registration: clinicaltrials.gov Identifier: NCT00280566.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antimanic Agents / administration & dosage*
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / adverse effects
  • Bipolar Disorder / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination / adverse effects
  • Female
  • Humans
  • Lithium Compounds / administration & dosage*
  • Male
  • Middle Aged
  • Piperazines / administration & dosage*
  • Piperazines / adverse effects
  • Placebos
  • Psychiatric Status Rating Scales
  • Severity of Illness Index
  • Thiazoles / administration & dosage*
  • Thiazoles / adverse effects
  • Treatment Outcome
  • Valproic Acid / administration & dosage*

Substances

  • Antimanic Agents
  • Antipsychotic Agents
  • Lithium Compounds
  • Piperazines
  • Placebos
  • Thiazoles
  • Valproic Acid
  • ziprasidone

Associated data

  • ClinicalTrials.gov/NCT00280566