Major Depressive Disorder

To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) as monotherapy treatment for major depressive disorder (MDD). This 8-week (6-week active-treatment, randomized phase; 2-week posttreatment drug-discontinuation/tapering phase), multicenter, double-blind, randomized, parallel-group, placebo- and active-controlled, phase 3 study was conducted between April 2006 and May 2007. In total, 612 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-defined MDD were randomly assigned to quetiapine XR 150 mg/day or 300 mg/day, duloxetine 60 mg/day (active control), or placebo. The primary endpoint was the change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. At week 6, both doses of quetiapine XR (p < .001) and duloxetine (p < .01) significantly reduced mean MADRS total score versus placebo. A significant reduction was seen at week 1 with quetiapine XR 150 mg/day and 300 mg/day versus placebo (p < .01), but not with duloxetine. Response rates (>or= 50% reduction in MADRS total score) at week 6 were significantly higher for both doses of quetiapine XR (p < .01) and duloxetine (p < .05) versus placebo. Remission rates (MADRS score <or= 8) were significantly higher for quetiapine XR 300 mg/day and duloxetine versus placebo (p < .05), but not for quetiapine XR 150 mg/day. Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Clinical Global Impressions-Severity of Illness total scores and the proportion of patients with Clinical Global Impressions-Improvement scores of 1 or 2 ("much/very much improved") were significantly improved with both doses of quetiapine XR and duloxetine versus placebo. The most common adverse events reported were dry mouth, sedation, and somnolence for quetiapine XR and nausea, headache, dizziness, and dry mouth for duloxetine. Quetiapine XR monotherapy (150 mg/day and 300 mg/day) is effective, with safety and tolerability consistent with the known profile of quetiapine XR, in the treatment of patients with MDD, with onset of symptom improvement demonstrated at week 1. clinicaltrials.gov Identifier: NCT00321490.