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

• Published in: The American journal of geriatric psychiatry 2013-08, Vol.21 (8), p.769-784
• Main Authors: Katila, Heikki, M.D, Mezhebovsky, Irina, M.D, Mulroy, Amy, M.D, Berggren, Lovisa, M.Sc, Eriksson, Hans, M.D., Ph.D., M.B.A, Earley, Willie, M.D, Datto, Catherine, M.D., M.S
• Format: Article
• Language: English
• Subjects: Aged; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Atypical antipsychotic; Delayed-Action Preparations - adverse effects; Delayed-Action Preparations - therapeutic use; Depressive Disorder, Major - drug therapy; Dibenzothiazepines - administration & dosage; Dibenzothiazepines - adverse effects; Dibenzothiazepines - therapeutic use; Double-Blind Method; elderly; extended release; Female; Humans; Internal Medicine; major depressive disorder; Male; Quetiapine Fumarate; quetiapine XR
• ISSN: 1064-7481; 1545-7214
• DOI: 10.1016/j.jagp.2013.01.010

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.