Randomized, placebo-controlled trial of risperidone for acute treatment of bipolar anxiety

J Affect Disord. 2009 Jun;115(3):376-85. doi: 10.1016/j.jad.2008.10.005. Epub 2008 Nov 29.


Background: The treatment of bipolar disorder is often complicated by the presence of a co-occuring anxiety disorder. Although second generation antipsychotics are being used with increasing frequency in bipolar patients, their anxiolytic effects have not been well studied in this population.

Methods: The anxiolytic effect of risperidone 0.5-4 mg/day was tested in an 8-week, double-blind, placebo-controlled, randomized clinical trial in 111 patients with bipolar disorder and a co-occuring panic disorder or generalized anxiety disorder (GAD). The primary outcome measure was the Clinician Global Improvement-21 Anxiety scale (CGI-21 Anxiety). Secondary measures included the Hamilton Anxiety Scale (HAM-A) and the Sheehan Panic Disorder Scale.

Results: On the last-observation-carried forward analysis of repeated measures analysis of variance (ANOVA), risperidone was not more effective than placebo for the CGI-21 Anxiety score or the other anxiety outcome measures. Risperidone was well tolerated, with only two patients withdrawing because of adverse events.

Limitations: The risperidone treated group had more patients with mixed states and lifetime panic disorder at randomization than the placebo group. The study was limited to 8 weeks and to individuals with bipolar and comorbid panic disorder or GAD. The results may not be applicable to risperidone as an add-on treatment to mood stabilizers, or to bipolar disorder comorbid with anxiety disorders other than panic disorder or GAD.

Conclusions: Risperidone monotherapy was not an effective anxiolytic for bipolar patients with comorbid panic disorder or GAD in doses of 0.5-4 mg/day over 8 weeks of treatment. The efficacy of other second generation antipsychotics and mood stabilizers on anxiety in patients with bipolar disorder and a co-occuring anxiety disorder should be investigated in double-blind, placebo-controlled studies.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Anxiety / drug therapy*
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / psychology
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / psychology
  • Comorbidity
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Panic Disorder / drug therapy
  • Psychiatric Status Rating Scales
  • Risperidone / administration & dosage
  • Risperidone / adverse effects
  • Risperidone / therapeutic use*
  • Serotonin Antagonists / administration & dosage
  • Serotonin Antagonists / adverse effects
  • Serotonin Antagonists / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Serotonin Antagonists
  • Risperidone