Efficacy and safety of levomilnacipran, vilazodone and vortioxetine compared with other second-generation antidepressants for major depressive disorder in adults: A systematic review and network meta-analysis

Background Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are the latest therapeutic options approved for the treatment of MDD. This systematic review aims to compare the benefits and harms of vilazodone, levomilnacipran, and vortioxetine with one another and other second-generation antidepressants. Methods We searched electronic databases up to September 2017 and reviewed reference lists and pharmaceutical dossiers to detect published and unpublished studies. Two reviewers independently screened abstracts and full text articles, and rated the risk of bias of included studies. Randomized controlled trials (RCTs) and controlled observational studies including adult outpatients with MDD were eligible for inclusion. We conducted network meta-analyses on response to treatment using frequentist multivariate meta-analyses models. Placebo- and active-controlled trials were eligible for network meta-analyses. Results Twenty-four studies met our inclusion criteria. Direct comparisons were limited to vilazodone versus citalopram, and vortioxetine versus duloxetine, paroxetine, or venlafaxine XR (extended release). Results of head-to-head trials and network meta-analyses, overall, indicated similar efficacy among levomilnacipran, vilazodone, or vortioxetine and other second-generation antidepressants. Although rates of overall adverse events and discontinuation due to adverse events were similar, RCTs reported several differences in specific adverse events. For most outcomes the strength of evidence was low. Limitations Limitations are the focus of literature searches on studies published in English, possible reporting biases, and general methodological limitations of network meta-analyses. Conclusions Overall, the available evidence does not indicate greater benefits or fewer harms of levomilnacipran, vilazodone, and vortioxetine compared with other second-generation antidepressants.