Randomized, Placebo-Controlled Effectiveness Study of Quetiapine XR in Comorbid Depressive and Anxiety Disorders.

Objective: Quetiapine is approved as an adjunctive treatment for major depressive disorder (MDD) and as monotherapy for bipolar depression. It is often used off-label for treating anxiety conditions and as an augmentation agent for treatment-resistant depression. However, its benefit in depression with comorbid anxiety disorders has not been systematically evaluated. The current study evaluated the benefit and tolerability of quetiapine as augmentation to first-line antidepressants for MDD comorbid with anxiety disorders.Methods: In this multicenter trial (June 2008-June 2013), 76 adults (aged 18-65 years) with a primary diagnosis of unipolar depression comorbid with at least 1 anxiety disorder (per DSM-IV-TR criteria) received flexible-dose quetiapine extended-release (XR) 50-300 mg/d or placebo as add-on for 12 weeks in a 2:1 ratio. Depression, anxiety, life satisfaction, and adverse events were assessed.Results: Depression, anxiety, and function improved significantly in both groups. On primary outcome measures, quetiapine was superior to placebo in improving depression (17-item Hamilton Depression Rating Scale score: mean difference = -3.64; 95% CI, -7.01 to -0.27) and anxiety symptoms (Hamilton Anxiety Rating Scale score: mean difference = -4.02; 95% CI, -7.41 to -0.64), as well as Clinical Global Impressions-Severity of Illness scale score (mean difference = -0.64; 95% CI, -1.13 to -0.15). On secondary measures including the Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, Penn State Worry Questionnaire, and Quality of Life Satisfaction and Enjoyment Questionnaire, quetiapine produced a greater degree of improvement compared to placebo, but group differences were not statistically significant. Quetiapine was well tolerated, with mostly minor and no serious adverse effects.Conclusions: Quetiapine augmentation may be a useful intervention for MDD with comorbid anxiety.Trial Registration: ClinicalTrials.gov Identifier: NCT00688818.

Evaluation of the feasibility of switching from immediate release quetiapine to extended release quetiapine fumarate in stable outpatients with schizophrenia.

This double-blind, double-dummy study (D1444C00146) evaluated the efficacy and safety of switching patients with clinically stable schizophrenia from quetiapine immediate release (IR) to the same dose of once-daily extended release quetiapine fumarate (quetiapine XR). Patients received quetiapine IR 400-800 mg/day twice daily for 4 weeks, and were then randomized (2 : 1) to a once-daily equivalent dose of quetiapine XR or maintained on IR for 6 weeks. The primary variable was the proportion of patients who discontinued treatment owing to lack of efficacy or whose Positive and Negative Syndrome Scale scores increased by at least 20% from randomization to any visit. In total, 497 patients were randomized to quetiapine XR (n=331) or IR (n=166). Noninferiority (6% margin; one-sided test, 2.5% significance level) was narrowly missed for the primary efficacy variable for the modified intention-to-treat population (9.1%, quetiapine XR; 7.2%, quetiapine IR; difference 1.86%; 95% confidence interval: -3.78, 6.57; P=0.0431), but was shown for the per-protocol population (5.3%, quetiapine XR; 6.2%, quetiapine IR; difference: -0.83%; 95% confidence interval: -6.75, 3.71; P=0.0017). Serious adverse event incidence was low for quetiapine XR and IR; there were no unexpected adverse events. In conclusion, efficacy was maintained without compromising safety/tolerability when switching patients with stable schizophrenia from twice-daily quetiapine IR to once-daily quetiapine XR (400-800 mg/day).