Efficacy of aripiprazole versus placebo as adjuncts to lithium or valproate in relapse prevention of manic or mixed episodes in bipolar I patients stratified by index manic or mixed episode

J Affect Disord. 2013 May;147(1-3):365-72. doi: 10.1016/j.jad.2012.11.042. Epub 2013 Jan 3.


Background: Differences in response to treatment have been observed for bipolar disorder (BPD) patients with manic or mixed episodes. This post-hoc analysis examined the maintenance effect of aripiprazole in combination with lithium or valproate in subpopulations of patients entering a relapse prevention study with either manic or mixed bipolar episodes.

Methods: A long-term relapse prevention study of BPD patients with manic or mixed episodes included a single-blind stabilization phase, in which patients were stabilized with single-blind aripiprazole plus lithium or valproate (maintaining stability for 12 weeks), and a double-blind relapse assessment phase, where patients were randomized to aripiprazole or placebo plus lithium or valproate for up to 52 weeks. Lithium and valproate groups were pooled.

Results: The time to relapse of any mood episode was longer in the adjunctive aripiprazole group versus the lithium/valproate monotherapy group for the manic (p<0.01) but not mixed population (p=0.59). The LOCF analysis indicated a significantly greater reduction in YMRS total score from baseline with continued aripiprazole versus placebo at 52 weeks in both manic (treatment difference=-3.32, p<0.01) and mixed episode populations (treatment difference=-2.56, p=0.02). Overall, adverse event profiles were similar between the populations.

Limitation: The lithium and valproate subgroups were combined.

Conclusions: The continuation of aripiprazole in stabilized BPD patients treated with lithium or valproate increased the time to relapse of any mood episode for manic but not mixed patients; both groups achieved greater stability in YMRS total score with adjunctive aripiprazole. Thus, adjunctive aripiprazole may be more appropriate for stabilized patients with manic episodes.

Publication types

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

MeSH terms

  • Adult
  • Aripiprazole
  • Bipolar Disorder / prevention & control*
  • Bipolar Disorder / psychology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Lithium Compounds / therapeutic use*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Piperazines / therapeutic use*
  • Quinolones / therapeutic use*
  • Secondary Prevention
  • Single-Blind Method
  • Tranquilizing Agents / therapeutic use*
  • Valproic Acid / therapeutic use*


  • Lithium Compounds
  • Piperazines
  • Quinolones
  • Tranquilizing Agents
  • Valproic Acid
  • Aripiprazole