Effectiveness and Safety of Vortioxetine for the Treatment of Major Depressive Disorder in the Real World: A Systematic Review and Meta-Analysis

Abstract

Introduction: Major depressive disorder (MDD) is a highly prevalent and burdensome condition. This study aims to evaluate the effectiveness, tolerability, and safety of vortioxetine in treating MDD based on real-world data.

Methods: A systematic search of 8 electronic databases was performed from inception until October 2022 to identify real-world studies, excluding randomized controlled trials. We conducted subgroup, meta-regression, sensitivity analyses, publication bias, and quality assessments using the random-effects model. The effects were summarized by rates or standardized mean difference (SMD) with 95% confidence interval (CI).

Results: Of the 870 records identified, 11 studies (3139 participants) and 10 case reports or series were eligible for inclusion. Vortioxetine significantly relieved depression symptoms as assessed by both patients (SMD = 2.25, 95% CI = 1.60-2.89) and physicians (SMD = 3.73, 95% CI = 2.78-4.69). Cognitive function (SMD =1.86, 95% CI = 1.11-2.62) and functional disability (SMD =1.71, 95% CI = 1.14-2.29) were similarly markedly improved. Subgroup and meta-regression analyses showed that geographic location and medication regimen (whether combined with other antidepressants) were crucial factors influencing effectiveness (in terms of depression severity and cognitive function), potentially contributing to significant heterogeneity. The estimated response and remission rates were 66.4% (95% CI = 51.2%-81.5%) and 58.0% (95% CI = 48.9%-67.1%), respectively. Vortioxetine was well tolerated, with a pooled dropout rate of 3.5% (95% CI = 1.8%-5.8%), and the most common adverse event was nausea, with an estimated rate of 8.9% (95% CI = 3.8%-15.8%).

Limitations: The study has some limitations, including significant heterogeneity and limited evidence for some outcomes.

Conclusions: Vortioxetine is effective, well tolerated, and safe for treating MDD in clinical practice, with significant improvements observed in depressive severity, cognitive function, and functioning. Future studies should directly compare vortioxetine with other antidepressants in real-world settings to further evaluate its clinical utility.

Keywords: Vortioxetine; cognitive function; major depressive disorder; real world; safety.

Figure 1.

PRISMA 2020 flow diagram for identification of studies via databases.

Figure 2.

The forest plot of meta-analysis with vortioxetine treatment for major depressive disorder (MDD). (A) Improvement in depression severity (assessed using self-rated scales). (B) Improvement in depression severity (assessed using other rated scales). (C) Improvement in functional disability (assessed using the patient-reported Sheehan Disability Scale). (D) Improvement in cognitive function (assessed by the Perceived Deficits Questionnaire-Depression). (E) Incidence of nausea after transformation by double arcsine. (F) Remission rate after vortioxetine treatment. (G) Response rate after vortioxetine treatment.

Figure 3.

Subgroup analysis of improvement in depression severity (assessed using self-rated scales) (A) and cognitive function (B).