title: A meta-analysis of randomized, placebo-controlled trials of vortioxetine for the treatment of major depressive disorder in adults.
abstract: The efficacy and safety of vortioxetine, an antidepressant approved for the treatment of adults with major depressive disorder (MDD), was studied in 11 randomized, double-blind, placebo-controlled trials of 6/8 weeks׳ treatment duration. An aggregated study-level meta-analysis was conducted to estimate the magnitude and dose-relationship of the clinical effect of approved doses of vortioxetine (5-20mg/day). The primary outcome measure was change from baseline to endpoint in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Differences from placebo were analyzed using mixed model for repeated measurements (MMRM) analysis, with a sensitivity analysis also conducted using last observation carried forward. Secondary outcomes included MADRS single-item scores, response rate (≥50% reduction in baseline MADRS), remission rate (MADRS ≤10), and Clinical Global Impressions scores. Across the 11 studies, 1824 patients were treated with placebo and 3304 with vortioxetine (5mg/day: n=1001; 10mg/day: n=1042; 15mg/day: n=449; 20mg/day: n=812). The MMRM meta-analysis demonstrated that vortioxetine 5, 10, and 20mg/day were associated with significant reductions in MADRS total score (Δ-2.27, Δ-3.57, and Δ-4.57, respectively; p<0.01) versus placebo. The effects of 15mg/day (Δ-2.60; p=0.105) were not significantly different from placebo. Vortioxetine 10 and 20mg/day were associated with significant reductions in 9 of 10 MADRS single-item scores. Vortioxetine treatment was also associated with significantly higher rates of response and remission and with significant improvements in other depression-related scores versus placebo. This meta-analysis of vortioxetine (5-20mg/day) in adults with MDD supports the efficacy demonstrated in the individual studies, with treatment effect increasing with dose.
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. Electronic address: thase@mail.med.upenn.edu.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.affiliation: Takeda Development Center Americas, Deerfield, IL 60015, USA.
authors.forename: Atul R
authors.initials: AR
authors.lastname: Mahableshwarkar
authors.affiliation: H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Dragheim
authors.affiliation: H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Loft
authors.affiliation: Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010879:Piperazines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013440:Sulfides / Q000627:therapeutic use*; D016896:Treatment Outcome; D000078784:Vortioxetine
chemical_list: D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013440:Sulfides; D000078784:Vortioxetine
keywords: Clinical efficacy; Drug dose–response relationship; Major depressive disorder; Meta-analysis; Vortioxetine