Efficacy and safety of quetiapine-XR as monotherapy or adjunctive therapy to a mood stabilizer in acute bipolar depression with generalized anxiety disorder and other comorbidities: a randomized, placebo-controlled trial.

Objective: To study the efficacy and safety of quetiapine-XR as monotherapy or adjunctive therapy to a mood stabilizer in acute bipolar I or II depression with comorbid generalized anxiety disorder (GAD) and other comorbidities.

Method: The study was conducted from January 2007 to November 2011. The Mini-International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV bipolar disorder, GAD, and other Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. The Hamilton Depression Rating Scale-17 items (HDRS-17) was used as a primary outcome to evaluate the difference between the 2 groups using the change from baseline to end of study. Last observation carried forward and mixed-effects modeling for repeated measures were used to analyze the primary and secondary outcome measures.

Results: Of the 120 patients screened, 100 patients were randomized to receive quetiapine-XR (n = 50) or placebo (n = 50). Twenty-six patients in the quetiapine-XR and 18 in the placebo group completed the study. The mean quetiapine-XR dose was 276 ± 50 mg/d (50-300 mg/d). There was no significant difference between the 2 groups in the change from baseline to end of study in HDRS-17 total score with an effect size of 0.19 favoring quetiapine-XR. There were also no significant differences between the 2 groups in secondary efficacy and safety outcome measures.

Conclusions: Quetiapine-XR was not significantly superior to placebo in bipolar I or II depression with GAD and other comorbidities, suggesting that data from relatively "pure" bipolar patients may not be generalizable to a highly comorbid population.

Trial Registration: ClinicalTrials.gov identifier: NCT00671853.