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

Author(s): Sheehan DV(1), Harnett-Sheehan K, Hidalgo RB, Janavs J, McElroy SL, Amado D, Suppes T.

Affiliation(s): Author information: (1)Clinical and Translational Science Institute, University of South Florida, College of Medicine, 3515 East Fletcher Ave, Tampa, FL 33613, USA. dsheehan@health.usf.edu

Publication date & source: 2013, J Affect Disord. , 145(1):83-94

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.