A Randomized, Double-blind Study of the Efficacy and Tolerability of Extended Release Quetiapine Fumarate (Quetiapine XR) Monotherapy in Patients with Major Depressive Disorder

Objectives: Evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD). Methods: 10-week (8-week active-treatment/2-week post-treatment), randomized, double-blind, placebo- and active-controlled study (D1448C00004). Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in MADRS total score) at Week 2 received double-treatment dose. Primary endpoint: Week 8 change from randomization in MADRS total score. Secondary endpoints included: MADRS response (>= 50% improvement) and remission (score <= 8), HAM-D total and Item 1, HAM-A total, psychic and somatic, CGI-S total, PSQI global, and Q-LES-Q-SF% maximum total scores; tolerability was assessed throughout. Results: 471 patients were randomized. No significant improvements in MADRS total score were observed at Week 8 (LOCF) with either active treatment (quetiapine XR, -17.21 [p = 0.174]; escitalopram, -16.73 [p = 0.346]) versus placebo (-15.61). There were no significant differences in secondary endpoints versus placebo, with the exception of Week 8 change in PSQI global score (quetiapine XR, -4.96 [p < 0.01] versus placebo, -3.37). MMRM analysis of observed cases data suggested that the primary analysis may not be robust. Most commonly reported AEs included: dry mouth, somnolence, and dizziness for quetiapine XR; headache and nausea for escitalopram. Conclusions: In this study, neither quetiapine XR (150/300 mg/day) nor escitalopram 10/20 mg/day) showed significant separation from placebo. Both compounds have been shown previously to be effective in the treatment of MDD; possible reasons for this failed study are discussed. Quetiapine XR was generally well tolerated with a profile similar to that reported previously. Psychopharmacology Bulletin. 2012;45(1):5-30.