INTRODUCTION: Vortioxetine is an antidepressant with multimodal activity which 
has shown efficacy in major depressive disorder (MDD) patients in six of ten 
short-term, randomized, placebo-controlled trials (completed end 2012).
METHODS: We performed meta-regression analyses to indirectly compare 
vortioxetine to seven marketed antidepressants with different mechanisms of 
action. To ensure study comparability, only experimental drug and placebo arms 
from placebo-controlled registration studies were included in primary analyses. 
The main outcomes were efficacy (standardized mean difference in change from 
baseline to 2 months on primary endpoint [MADRS/HAM-D]), and tolerability 
(withdrawal rate due to adverse events).
RESULTS: For efficacy, estimates of treatment effect (negative estimates favor 
vortioxetine) for vortioxetine versus comparators were: agomelatine, -0.16 (p = 
0.11); desvenlafaxine, 0.03 (p = 0.80); duloxetine, 0.09 (p = 0.42); 
escitalopram, -0.05 (p = 0.70); sertraline, -0.04 (p = 0.83); venlafaxine IR/XR, 
0.12 (p = 0.33); and vilazodone, -0.25 (p = 0.11). For tolerability, all but one 
combination was numerically in favor of vortioxetine (odds ratio < 1), although 
not all differences were statistically significant: agomelatine, 1.77 (p = 
0.03); desvenlafaxine, 0.58 (p = 0.04); duloxetine, 0.75 (p = 0.26); 
escitalopram, 0.67 (p = 0.28); sertraline, 0.30 (p = 0.01); venlafaxine, 0.47 (p 
= 0.01); and vilazodone, 0.64 (p = 0.18). Sensitivity analyses did not 
significantly alter antidepressant effect estimates or relative ranking.
CONCLUSION: These meta-regression data show that vortioxetine offers a 
comparable or favorable combination of efficacy (measured by MADRS/HAM-D) and 
tolerability (measured by withdrawal rate due to adverse events) versus other 
antidepressants in registration studies in MDD. Alternative methods like 
mixed-treatment comparison and inclusion of all randomized studies and active 
reference arms may provide complementary information to this analysis (more 
evidence but also more heterogeneity). Key messages: Indirect comparisons based 
on registration studies allow a useful comparison between a recently approved 
antidepressant and an approved drug. Vortioxetine offers a comparable or 
favorable combination of efficacy (measured by MADRS/HAM-D assessments) and 
tolerability (measured by withdrawal rate due to adverse events) versus other 
antidepressants in registration studies in MDD.