Efficacy and tolerability of different doses of three new antidepressants for treating major depressive disorder: A PRISMA-compliant meta-analysis

In last decade, the US FDA has approved three new antidepressants: vortioxetine, levomilnacipran, and vilazodone. Many studies have researched the effects of these antidepressants on major depressive disorder (MDD), but they have not determined the optimum dosage. This meta-analysis investigated the efficacies of these three drugs at different dosages in the treatment of MDD. The PubMed, Embase, Cochrane Library, psycINFO, and ClinicalTrials.gov databases were searched to identify relevant literature. The primary outcomes were efficacy [quantified as the change from baseline in total score on the Montgomery-Asberg Depression Rating Scale (MADRS)] and tolerability (discontinuations due to adverse events). The effect size was quantified as the weighted mean difference for continuous data and the risk ratio (RR) for dichotomous data. Overall 22 studies were included. The changes in the MADRS total score were significantly higher for vortioxetine at 5, 10, 20, and 10–20 mg/day than for placebo. The tolerability was significantly worse for 20 mg/day vortioxetine than for placebo (RR = 1.84, 95% confidence interval = 1.13 to 3.02). In addition, increasing the dosage improved the efficacy of vortioxetine but worsened the tolerability. Levomilnacipran and vilazodone at any dosage produced a significantly higher mean change from baseline in the MADRS total score and a worse tolerability than for placebo. In conclusion, considering both efficacy and tolerability, 10 mg/day vortioxetine might be optimal for the treatment of MDD. The long-term efficacy and safety of vortioxetine needed to be investigated, and more studies of levomilnacipran and vilazodone are needed to define their optimal dosages.