Extended-Release Quetiapine as Adjunct to an Antidepressant in Patients With Major Depressive Disorder: Results of a Randomized, Placebo-Controlled, Double-Blind Study

Objective: This 6-week, randomized, double-blind study evaluated efficacy and safety of adjunctive extended-re lease (XR) quetiapine in patients with major depressive disorder (MDD) and an inadequate response to >= 1 antidepressant. Method: Male or female patients aged 18 to 65 years with DSM-IV-TR MDD were randomly assigned to receive quetiapine XR (150 or 300 mg/day) or placebo adjunctive to continuing antidepressant. Primary endpoint was change from randomization to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. Secondary variables included MADRS response (>= 50% reduction in score from randomization) at weeks 1 and 6, MADRS remission (<= 8 total score) at week 6, and week 6 change in Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety total scores. Safety was assessed throughout the study. The study was conducted between May 8, 2006, and April 7, 2007. Results: Four hundred ninety-three patients were randomly assigned. Mean change from randomization to week 6 in MADRS score was -15.26 and -14.94 for quetiapine XR 150 mg/day and 300 mg/day, respectively (both p <.01 vs. placebo [-12.21]). Quetiapine XR showed separation from placebo in MADRS score from week 1 (p < .001) onward. The MADRS response rates were 55.4%, 57.8%, and 46.3% for quetiapine XR 150 mg/day (p = .107 vs. placebo), 300 mg/day (p < .05), and placebo, respectively; MADRS remission rates were 36.1% (p < .05 vs. placebo), 31.1% (p = .126), and 23.8% for quetiapine XR 150 mg/day, 300 mg/day, and placebo, respectively. Withdrawal rates due to adverse events were 6.6%, 11.7%, and 3.7% with quetiapine XR 150 mg/day, 300 mg/day, and placebo, respectively. The most common adverse events were dry mouth (20.4%, 35.6%, and 6.8%) and somnolence (16.8%, 23.3%, and 3.1%). Conclusions: Adjunctive quetiapine XR (150 mg/day and 300 mg/day) was effective in patients with MDD who had shown an inadequate response to antidepressant treatment. Significant reduction of depressive symptoms occurred as early as week 1. Findings were consistent with the known safety and tolerability profile of quetiapine.