A meta-analysis of randomized, placebo-controlled trials of vortioxetine for the treatment of major depressive disorder in adults

作者：Thase Michael E; Mahableshwarkar Atul R; Dragheim Marianne; Loft Henrik; Vieta Eduard

来源：European Neuropsychopharmacology, 2016, 26(6): 979-993.

DOI：10.1016/j.euroneuro.2016.03.007

• Vortioxetine
• Major depressive disorder
• Clinical efficacy
• Meta-analysis
• Drug dose-response relationship

The efficacy and safety of vortioxetine, an antidepressant approved for the treatment of adults with major depressive disorder (MDD), was studied in 11 randomized, double-blind, placebo controlled trials of 6/8 weeks' treatment duration. An aggregated study-level meta-analysis was conducted to estimate the magnitude and dose-relationship of the clinical effect of approved doses of vortioxetine (5-20 mg/day). The primary outcome measure was change from baseline to endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) total score. Differences from placebo were analyzed using mixed model for repeated measurements (MMRM) analysis, with a sensitivity analysis also conducted using last observation carried forward. Secondary outcomes included MADRS single-item scores, response rate (>= 50% reduction in baseline MADRS), remission rate (MADRS <= 10), and Clinical Global Impressions scores. Across the 11 studies, 1824 patients were treated with placebo and 3304 with vortioxetine (5 mg/day: n=1001; 10 mg/day: n=1042; 15 mg/day: n=449; 20 mg/day: n=812). The MMRM meta analysis demonstrated that vortioxetine 5, 10, and 20 mg/day were associated with significant reductions in MADRS total score (Delta-2.27, Delta-3.57, and Delta-4.57, respectively; p <0.01) versus placebo. The effects of 15 mg/day (Delta-2.60; p=0.105) were not significantly different from placebo. Vortioxetine 10 and 20 mg/day were associated with significant reductions in 10 of 10 MADRS single-item scores. Vortioxetine treatment was also associated with significantly higher rates of response and remission and with significant improvements in other depression-related scores versus placebo. This meta-analysis of vortioxetine (5-20 mg/day) in adults with MDD supports the efficacy demonstrated in the individual studies, with treatment effect increasing with dose.

• 出版日期2016-6