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 (5-20mg/day). The primary outcome measure was change from baseline to endpoint in Montgomery-Åsberg 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 (5mg/day: n=1001; 10mg/day: n=1042; 15mg/day: n=449; 20mg/day: n=812). The MMRM meta-analysis demonstrated that vortioxetine 5, 10, and 20mg/day were associated with significant reductions in MADRS total score (Δ-2.27, Δ-3.57, and Δ-4.57, respectively; p<0.01) versus placebo. The effects of 15mg/day (Δ-2.60; p=0.105) were not significantly different from placebo. Vortioxetine 10 and 20mg/day were associated with significant reductions in 9 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 (5-20mg/day) in adults with MDD supports the efficacy demonstrated in the individual studies, with treatment effect increasing with dose.
Keywords: Clinical efficacy; Drug dose–response relationship; Major depressive disorder; Meta-analysis; Vortioxetine.
Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.