Risperidone long-acting injectable monotherapy in the maintenance treatment of bipolar I disorder

Biol Psychiatry. 2010 Jul 15;68(2):156-62. doi: 10.1016/j.biopsych.2010.01.015. Epub 2010 Mar 15.


Background: Treatment adherence is a significant problem in patients with bipolar disorder. This study was designed to determine the efficacy of risperidone long-acting injectable (LAI) in the maintenance treatment of bipolar I disorder.

Methods: Eligible patients with current or recent manic or mixed episodes (n = 559, aged 18-65 years) were treated with open-label oral risperidone for 3 weeks (period II) and open-label risperidone LAI for 26 weeks (n = 501; period III). Patients who maintained response (n = 303) were randomly allocated 1:1 to placebo injections (n = 149) or to continue risperidone LAI (n = 154) for up to 24 months (period IV).

Results: Most (77%) patients on risperidone LAI received a dose of 25 mg every 2 weeks during period IV. Time to recurrence for any mood episode (primary outcome variable) was significantly longer in the risperidone LAI group versus placebo (p < .001); the difference was significant for time to recurrence of elevated-mood episode (p < .001) but not time to recurrence of depressive episode (p = .805). Weight gains > or = 7% (compared with the period's baseline) occurred in 15% of patients in period III; in 12% of patients on risperidone LAI and 3% of patients on placebo in period IV.

Conclusions: Risperidone LAI monotherapy significantly delayed the time to recurrence of mood episodes, versus placebo, in this controlled, randomized study in patients with bipolar I disorder. Risperidone LAI was tolerable and no new safety concerns emerged compared with previous studies of risperidone LAI.

Trial registration: ClinicalTrials.gov NCT00132678.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use
  • Bipolar Disorder / drug therapy*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Injections, Intramuscular
  • Kaplan-Meier Estimate
  • Male
  • Medication Adherence
  • Middle Aged
  • Risperidone / administration & dosage*
  • Risperidone / therapeutic use
  • Treatment Outcome


  • Antipsychotic Agents
  • Risperidone

Associated data

  • ClinicalTrials.gov/NCT00132678