Gang Wang1, Alexander McIntyre1, Willie R Earley1, Shane Raines1, Hans Eriksson1. 1. Dr. Wang, MD, PhD, Beijing Anding Hospital, Capital Medical University, Xicheng District, Beijing, China. Dr. McIntyre, FRCPC, Department of Psychiatry, Penticton Regional Hospital, Penticton, British Columbia, Canada. Dr. Earley, MD, Mr. Raines, MS, AstraZeneca Pharmaceuticals, Wilmington, DE. Dr. Eriksson, MD, PhD, MBA, AstraZeneca R&D, Södertälje, Sweden.
Abstract
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.
RCT Entities:
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.
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