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.