BACKGROUND: This 8-week, randomized, double-blind, placebo-controlled study, 
conducted August 2010-May 2012 in the United States, evaluated the safety and 
efficacy of vortioxetine 10 mg and 15 mg in patients with major depressive 
disorder (MDD). The mechanism of action of vortioxetine is thought to be related 
to direct modulation of serotonin (5-HT) receptor activity and inhibition of the 
serotonin transporter.
METHOD: Adults aged 18-75 years with MDD (DSM-IV-TR) and Montgomery-Asberg 
Depression Rating Scale (MADRS) total score ≥ 26 were randomized (1:1:1) to 
receive vortioxetine 10 mg or 15 mg or placebo once daily, with the primary 
efficacy end point being change from baseline at week 8 in MADRS analyzed by 
mixed model for repeated measures. Adverse events were recorded during the 
study, suicidal ideation and behavior were assessed using the Columbia-Suicide 
Severity Rating Scale (C-SSRS), and sexual dysfunction was assessed using the 
Arizona Sexual Experience (ASEX) scale.
RESULTS: Of the 1,111 subjects screened, 469 subjects were randomized: 160 to 
placebo, 157 to vortioxetine 10 mg, and 152 to vortioxetine 15 mg. Differences 
from placebo in the primary efficacy end point were not statistically 
significant for vortioxetine 10 mg or vortioxetine 15 mg. Nausea, headache, dry 
mouth, constipation, diarrhea, vomiting, dizziness, and flatulence were reported 
in ≥ 5% of subjects receiving vortioxetine. Discontinuation due to adverse 
events occurred in 7 subjects (4.4%) in the placebo group, 8 (5.2%) in the 
vortioxetine 10 mg group, and 12 (7.9%) in the vortioxetine 15 mg group. ASEX 
total scores were similar across groups. There were no clinically significant 
trends within or between treatment groups on the C-SSRS, laboratory values, 
electrocardiogram, or vital sign parameters.
CONCLUSIONS: In this study, vortioxetine did not differ significantly from 
placebo on MADRS total score after 8 weeks of treatment in MDD subjects.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01179516.