Characterizing relapse prevention in bipolar disorder with adjunctive ziprasidone: clinical and methodological implications

J Affect Disord. 2013 Jan 10;144(1-2):171-5. doi: 10.1016/j.jad.2012.04.024. Epub 2012 Sep 21.

Abstract

Background: Ziprasidone, adjunctive to either lithium or valproate, has previously been shown to be associated with a significantly lower risk of relapse in bipolar disorder compared with lithium or valproate treatment alone.

Methods: This placebo-controlled outpatient trial with ziprasidone adjunctive to lithium or valproate or lithium and valproate alone, for subjects with a recent or current manic or mixed episode of bipolar I disorder, comprised a 2.5- to 4-month, open-label stabilization period, followed by a 6-month, double-blind maintenance period. These post hoc analyses characterize the relapse outcomes by dose, relapse types and timing as well as all-reason discontinuations during the maintenance period.

Results: Time to relapse and all-reason discontinuation were both statistically significant in favor of the ziprasidone 120mg/day group compared with placebo (p=0.004 and 0.001, respectively) during the 6-month double-blind period. There was no difference in time to relapse in the 80 and 160mg/day dose groups compared with placebo (p=0.16 and 0.40, respectively) and, likewise, for time to all-reason discontinuation (p=0.20 for both doses). The majority of relapses in each group occurred prior to week 8, and most were depressive in nature.

Limitations: The primary study was not designed to compare relapse rates by dose groups.

Conclusions: These analyses confirm the effectiveness of ziprasidone (80-160mg/day) in preventing relapses in subjects with bipolar disorder, with the 120mg/day dosage appearing to have the highest relapse prevention rate.

Publication types

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

MeSH terms

  • Antipsychotic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / prevention & control
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination / methods
  • Follow-Up Studies
  • Humans
  • Lithium / therapeutic use*
  • Piperazines / therapeutic use*
  • Secondary Prevention
  • Thiazoles / therapeutic use*
  • Treatment Outcome
  • Valproic Acid / therapeutic use*

Substances

  • Antipsychotic Agents
  • Piperazines
  • Thiazoles
  • Valproic Acid
  • ziprasidone
  • Lithium