BACKGROUND: Vortioxetine was approved by the U.S. Food and Drug Administration 
(FDA) in September 2013 for treating major depressive disorder (MDD). Thus far, 
a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) 
of vortioxetine have been conducted in patients with MDD. We performed a 
meta-analysis to increase the statistical power of these studies and enhance our 
current understanding of the role of vortioxetine in the treatment of MDD.
METHODS: We performed an extensive search of databases and the clinical trial 
registry. The mean change in total scores on the 24-item Hamilton Rating Scale 
for Depression (HAM-D) and the Montgomery- Åsberg Depression Rating Scale 
(MADRS) from the baseline were the primary outcome measures. The secondary 
efficacy measures were the response and remission rates, as defined by a 50% or 
greater reduction in HAM-D/MADRS total scores and as a score of 10 or less in 
the MADRS and 7 or less in the HAM-D total scores at the end of treatment.
RESULTS: We included 7 published and 5 unpublished short-term (6-12 wk) RCTs in 
our meta-analysis. Vortioxetine was significantly more effective than placebo, 
with an effect size (standardized mean difference [SMD]) of -0.217 (95% 
confidence interval [CI] -0.313 to -0.122) and with odds ratios (ORs) for 
response and remission of 1.652 (95% CI 1.321 to 2.067) and 1.399 (95% CI 1.104 
to 1.773), respectively. Those treated with vortioxetine did not differ 
significantly from those treated with selective norepinephrine reuptake 
inhibitors/agomelatine with regard to the SMD of the primary outcome measure 
(0.081, -0.062 to 0.223) or for response (OR 0.815, 95% CI 0.585 to 1.135) and 
remission (OR 0.843, 95% CI 0.575 to 1.238) rates. Discontinuation owing to lack 
of efficacy (OR 0.541, 95% CI 0.308 to 0.950) was significantly less common 
among those treated with vortioxetine than among those who received placebo, 
whereas discontinuation owing to adverse events (AEs; OR 1.530, 95% CI 1.144 to 
2.047) was significantly more common among those treated with vortioxetine than 
among those receiving placebo. There was no significant difference in 
discontinuation rates between vortioxetine and comparators owing to inefficacy 
(OR 0.983, 95% CI 0.585 to 1.650), whereas discontinuation owing to AEs was 
significantly less common in the vortioxetine than in the comparator group (OR 
0.728, 95% CI 0.554 to 0.957).
LIMITATIONS: Studies examining the role of vortioxetine in the treatment of MDD 
are limited.
CONCLUSION: Although our results suggest that vortioxetine may be an effective 
treatment option for MDD, they should be interpreted and translated into 
clinical practice with caution, as the meta-analysis was based on a limited 
number of heterogeneous RCTs.