Efficacy and Safety of Vortioxetine 15 and 20 mg in an 8-Week Placebo-Controlled and Duloxetine-Referenced Trial of Adults with Major Depressive Disorder

Objective: To assess the efficacy, tolerability, and safety of vortioxetine 15 and 20mg versus placebo in adults with major depressive disorder (MDD).
Methods: In this 8-week, double-blind, duloxetine-referenced trial, US adults with MDD were randomized to vortioxetine 15mg or 20mg, placebo or duloxetine 60mg daily. The primary efficacy endpoint was mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 8 (MMRM). Secondary endpoints included MADRS response, CGI-I score, MADRS total score in subjects with baseline HAM-A ≥20, MADRS remission, and SDS total score. Safety and tolerability assessments included adverse events (AEs), vital signs, Columbia-Suicide Severity Rating Scale (C-SSRS), Arizona Sexual Experience scale (ASEX) and Discontinuation-Emergent Signs and Symptoms (DESS) checklist.
Results: 614 subjects were randomized to placebo (161), vortioxetine 15mg (147), vortioxetine 20mg (154) and duloxetine 60mg (152). Vortioxetine 20mg significantly reduced mean change from baseline in MADRS total score at week 8 (-15.57), compared with placebo (-12.83, P=0.023) while vortioxetine 15mg (-14.30) was not significantly different from placebo (P=0.224). Duloxetine 60mg separated from placebo (P<0.001), confirming assay sensitivity. There were no significant differences in any key secondary endpoints. AEs reported in ≥5% of the vortioxetine groups were nausea, headache, dry mouth, dizziness, diarrhea, constipation, vomiting, insomnia, fatigue, nasopharyngitis, and respiratory tract infection. Vortioxetine was similar to placebo in ASEX, C-SSRS and DESS scores at week 8. 
Conclusions: In this trial of adults with MDD, vortioxetine 20mg significantly reduced MADRS total score after 8 weeks’ treatment. Both vortioxetine 15mg and 20mg were well tolerated.