Randomized, placebo-controlled trial of quetiapine XR and divalproex ER monotherapies in the treatment of the anxious bipolar patient

J Affect Disord. 2013 Feb 15;145(1):83-94. doi: 10.1016/j.jad.2012.07.016. Epub 2012 Aug 21.


Background: Anxiety disorders complicate the treatment of bipolar disorder but are seldom the focus of bipolar treatment studies.

Methods: The anxiolytic effect of quetiapine XR 50-300 mg/day compared to divalproex ER (500-3000 mg/day) was tested in an 8-week, double-blind, placebo-controlled, randomized clinical trial in 149 patients with bipolar disorder and a co-occurring panic disorder or GAD. The primary efficacy measure was the Clinician Global Improvement-21 Anxiety Scale (CGI-21). Secondary measures included the Hamilton Anxiety Scale (HAM-A) and Sheehan Panic Disorder Scale (SPS).

Results: Repeated measures last-observation-carried-forward (LOCF) analyses of variance demonstrated significant treatment-by-time interaction effects on 3 of the 4 anxiety measures. Quetiapine XR at a mean endpoint dose of 186 mg/day produced rapid sustained improvements relative to baseline, divalproex ER and placebo on anxiety. Mean baseline-to-endpoint improvement was significantly greater for quetiapine XR compared to divalproex ER and placebo on the HAM-A and SPS. Both active medications were well tolerated, but weight gain was higher on quetiapine XR.

Limitations: The study was limited to 8 weeks and to patients with bipolar disorder and comorbid panic disorder or GAD. The results may not be applicable to quetiapine XR as an add-on treatment to mood stabilizers or to bipolar disorder comorbid with other anxiety disorders.

Conclusions: Quetiapine XR in a dose range of 50-300 mg/day appears to reduce anxiety in bipolar patients with comorbid panic disorder or GAD treated for 8 weeks. The efficacy of other second-generation antipsychotics and mood stabilizers in patients with bipolar disorder and a co-occurring 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

  • Adult
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / adverse effects
  • Bipolar Disorder / complications
  • Bipolar Disorder / drug therapy*
  • Delayed-Action Preparations / administration & dosage
  • Dibenzothiazepines / administration & dosage*
  • Dibenzothiazepines / adverse effects
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Panic Disorder / complications
  • Panic Disorder / drug therapy*
  • Quetiapine Fumarate
  • Treatment Outcome
  • Valproic Acid / administration & dosage*
  • Valproic Acid / adverse effects
  • Weight Gain


  • Antipsychotic Agents
  • Delayed-Action Preparations
  • Dibenzothiazepines
  • Quetiapine Fumarate
  • Valproic Acid