Efficacy and adverse effect profile of vortioxetine in major depressive disorder: A meta-analysis

Background: Major depressive disorder (MDD) is a globally prevalent condition associated with significant morbidity and cognitive dysfunction. Vortioxetine, a novel antidepressant with multimodal serotonergic activity, has shown potential advantages over conventional antidepressants in both efficacy and tolerability. This meta-analysis evaluates the efficacy, cognitive improvement, and safety profile of vortioxetine in MDD. Methods: A comprehensive search of multiple search engines yielded 16 randomized controlled trials that studied the efficacy of vortioxetine and other antidepressants. About 3127 MDD patients in the vortioxetine group and 3102 in the control group were analyzed. Primary efficacy outcomes were changes in Montgomery-Åsberg Depression Rating Scale, Clinical Global Impression-Improvement, and Clinical Global Impression-Severity scores, and the secondary outcome measure was cognition using the digit symbol substitution test scores. Safety was assessed via reported adverse effects (AEs), including the treatment-induced sexual dysfunction. The sensitivity analysis was done excluding the study with a high impact. Results: Vortioxetine demonstrated a small but significant reduction in depressive symptoms compared to placebo, but showed similar efficacy to duloxetine and venlafaxine. Excluding the high-impact study did not cause much variation in the findings. There was a small but statistically insignificant improvement in cognition with vortioxetine compared to the control group. Vortioxetine had a favorable safety profile with only mild symptoms reported. The most commonly reported symptom was nausea. Vortioxetine also showed a non-significant trend toward fewer sexual AEs. Conclusion: Vortioxetine is an effective and well-tolerated antidepressant for the management of MDD. Though the tolerability was comparable to other antidepressants, there was a potentially lower incidence of sexual side effects. A further elaborate exploration in terms of dose-specific efficacy and cognitive improvement will be promising for optimizing individualized treatment strategies.