Randomized, double-blind study of the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder.

ABSTRACT

OBJECTIVES: This study assessed the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder (MDD). DESIGN: An 11-week (9-week randomized; 2-week posttreatment phase), double-blind, placebo-controlled, Phase III study (D1448C00014). SETTING: A total of 53 centers in Argentina, Estonia, Finland, Russia, Ukraine, and the United States. PARTICIPANTS: A total of 338 patients (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD, age ≥66 years, Hamilton Rating Scale for Depression [HAM-D] total score ≥22, HAM-D Item 1 [depressed mood] score ≥2) were randomized (mean age 71.3 years). INTERVENTION Patients were randomized to quetiapine XR (n = 166; flexible-dosing 50-300 mg/day) or placebo (n = 172). MEASUREMENTS Primary outcome was Montgomery Åsberg Depression Rating Scale (MADRS) total score change from randomization at Week 9. RESULTS: At Week 9, quetiapine XR (least squares [LS] means -16.33, standard error [SE] 0.95; mean change -16.0, standard deviation [SD] 9.3) significantly reduced MADRS total score from randomization versus placebo (LS means [SE] -8.79 [0.94]; mean [SD] -9.0 [9.9]); significant improvements were also seen at Week 1 (LS means [SE] -4.65 [0.53] versus -2.56 [0.53], respectively; mean [SD] -4.3 [5.1] versus -2.4 [3.7], respectively). At Week 9, secondary outcome variables significantly improved with quetiapine XR versus placebo, including MADRS response (≥50% reduction in total score); MADRS remission (total score ≤8); HAM-D total, HAM-A total, HAM-A psychic and somatic cluster, and Clinical Global Impressions-Severity of Illness (CGI-S) total scores; proportion of patients with CGI-Improvement score of 2 or less; Q-LES-Q-SF% maximum total, Pittsburgh Sleep Quality Index global, and pain Visual Analog Scale scores. Common adverse events (>10% patients with quetiapine XR) were somnolence, headache, dry mouth, and dizziness. CONCLUSION: In elderly patients with MDD, quetiapine XR monotherapy (50-300 mg/day, flexibly dosed) is effective at improving depressive symptoms, with symptom improvement observed as early as Week 1. Overall tolerability and safety were consistent with the known profile of quetiapine.