The safety and efficacy of vortioxetine for acute treatment of major depressive disorder: a systematic review and meta-analysis

Abstract

BackgroundVortioxetine is the first mixed serotonin agonist and antagonist antidepressant approved in the US. We sought to evaluate all published and unpublished data available to determine the efficacy and harms of vortioxetine in adults with major depressive disorder.MethodsWe used a predefined search strategy of MEDLINE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Drugs@FDA to identify studies evaluating vortioxetine in the acute treatment of major depressive disorder. Only randomized controlled trials (RCTs) that provided results on relevant clinical efficacy and safety outcomes were included. Study quality was assessed and results were pooled using mixed effect meta-analyses where applicable.ResultsWe identified 11 RCTs with 6,145 participants meeting inclusion criteria (eight were published and three were unpublished). The trials did not exceed 8 weeks in duration. The response rate with vortioxetine was significantly higher for 1-mg (relative risk (RR) = 1.91; 95% confidence interval (CI) 1.36 to 2.69), 5-mg (RR = 1.33; 95% CI 1.10 to 1.61), 10-mg (RR = 1.42; 95% CI 1.21 to 1.67), and 20-mg doses (RR = 1.58; 95% CI 1.19 to 2.08) compared to placebo. Remission rates were significantly higher for the 10-mg group (RR = 1.45; 95% CI 1.18 to 1.77) and the 20-mg group (RR = 1.68; 95% CI 1.19 to 2.37) compared to placebo. Meta-regression of dose on the log odds ratio of response was not statistically significant (β = 0.01; P = 0.46). Vortioxetine response rates were lower than active serotonin and norepinephrine reuptake inhibitor (SNRI) comparators for the 5-mg (RR = 0.88; 95% CI 0.80 to 0.98), 15-mg (RR = 0.78; 95% CI 0.68 to 0.90), and 20-mg (RR = 0.82; 95% CI 0.72 to 0.94) doses. The most common adverse events were nausea and vomiting which increased in frequency with higher doses.ConclusionsVortioxetine was significantly more effective than placebo for acute treatment of major depressive disorder (MDD). Although treatment effect estimates varied substantially between studies, a dose effect was not observed. Vortioxetine does not appear to be more effective, and is potentially less effective, than an SNRI.Systematic review registrationPROSPERO CRD42013006198.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-015-0001-y) contains supplementary material, which is available to authorized users.

The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature

“…vortioxetine, vilazodone and levomilnacipran) remain limited. Nevertheless, similarly to other antidepressant agents, nausea was one of the most frequently reported side effects [38,39,40]. …”

Low-Dose Combination of Aripiprazole for Treatment of Severe Depression with Cognitive Impairment: Case Report

“…Thus, in addition to difficulties in concentration, problems in decision making were recently specified within the diagnostic criteria of depression [9].Our case exemplifies the existence of cognitive deficits in depression regardless of cardinal humor symptoms. Recently, medications such as vortioxetine have been designed to treat both spheres of depression: cognition and mood [10][11][12]. However, the commercialization of this drug only began to be performed in Brazil in early 2016, that is after the treatment reported in this article.…”

What role for ▼vortioxetine?

“…A second meta-analysis (11 studies, 6,145 participants) showed that, compared with placebo, response rates were significantly higher with vortioxetine 5mg (relative risk [RR] 1.3, 95% CI 1.1 to 1.6), 10mg (RR 1.4, 95% CI 1.2 to 1.7) and 20mg (RR 1.6, 95% CI 1.2 to 2.1) but not with 15mg, and did not significantly increase with increasing dose 20. Compared with placebo, remission rates were higher with 10mg (RR 1.5, 95% CI 1.2 to 1.8) and 20mg doses (RR 1.7, 95% CI 1.2 to 2.4), but not with 5mg or 15mg.…”