This study assessed the efficacy, tolerability and safety of vortioxetine versus 
placebo in adults with recurrent major depressive disorder. This double-blind, 
randomized, placebo-controlled study included 608 patients [Montgomery-Åsberg 
Depression Rating Scale (MADRS) total score ≥ 26 and Clinical Global Impression 
- Severity score ≥ 4]. Patients were randomly assigned (1 : 1 : 1 : 1) to 
vortioxetine 15 mg/day, vortioxetine 20 mg/day, duloxetine 60 mg/day or placebo. 
The primary efficacy endpoint was change from baseline in MADRS total score at 
week 8 (mixed model for repeated measurements). Key secondary endpoints were: 
MADRS responders; Clinical Global Impression - Improvement scale score; MADRS 
total score in patients with baseline Hamilton Anxiety Rating Scale ≥ 20; 
remission (MADRS ≤ 10); and Sheehan Disability Scale total score at week 8. On 
the primary efficacy endpoint, both vortioxetine doses were statistically 
significantly superior to placebo, with a mean difference to placebo (n = 158) 
of -5.5 (vortioxetine 15 mg, P < 0.0001, n = 149) and -7.1 MADRS points 
(vortioxetine 20 mg, P < 0.0001, n = 151). Duloxetine (n = 146) separated from 
placebo, thus validating the study. In all key secondary analyses, both 
vortioxetine doses were statistically significantly superior to placebo. 
Vortioxetine treatment was well tolerated; common adverse events (incidence ≥ 
5%) were nausea, headache, diarrhea, dry mouth and dizziness. No clinically 
relevant changes were seen in clinical safety laboratory values, weight, ECG or 
vital signs parameters. Vortioxetine was efficacious and well tolerated in the 
treatment of patients with major depressive disorder.