Vortioxetine versus Placebo for Major Depressive Disorder: A Comprehensive Analysis of the Clinical Trial Dataset

Abstract

Objective: A meta-analysis of studies of vortioxetine in adults with major depressive disorder (MDD). Data Sources: Abstracts were identified using PubMed by cross-referencing “vortioxetine” with “placebo” and “randomized.” No language or publication year restrictions were used. Study Selection: Randomized, double-blind, placebo-controlled clinical trials comparing oral vortioxetine monotherapy with placebo for acute treatment of MDD. Data Extraction: Data were extracted with a pre-coded form, as follows: number of patients randomized, treatment group, Montgomery-Asberg Depression Rating Scale (MADRS) response and remission rates, mean change in scores from baseline and standard errors for the MADRS, Hamilton Anxiety Rating Scale (HAM-A), and Digit Symbol Substitution Test (DSST). Results: 7,269 subjects randomized to vortioxetine (n=3,630) or placebo (n=3,639) from 17 studies were included. The probability of receiving placebo did not predict difference in change in MADRS scores between vortioxetine and placebo (estimate 4.1, p=0.54). The standardized mean difference (SMD) (95% CI) for change in MADRS versus placebo was 0.33 (0.24 - 0.41), and was 0.25 (0.08 - 0.39), 0.33 (0.19 - 0.47), 0.26 (-0.06 to 0.58), and 0.44 (0.27 - 0.62) for 5mg, 10 mg, 15 mg, and 20 mg doses respectively. Greater difference in efficacy between drug and placebo was observed in studies with a low than a high placebo response rate. Conclusion: Vortioxetine is more effective than placebo in improving depression, anxiety and cognition. Less informative or uninformative studies obscured the true treatment effect.