Vortioxetine improves symptomatic and functional outcomes in major depressive disorder: A novel dual outcome measure in depressive disorders.

BACKGROUND: With symptomatic remission and functional recovery as the overarching therapeutic objectives of antidepressant therapy, composite endpoint measures that conjointly consider both aspects of treatment are needed. This analysis evaluated the combined effect of vortioxetine on depressive symptoms and functional capacity in adults with MDD.

METHODS: NCT01564862, a multinational, double-blind, placebo-controlled, duloxetine-referenced study, conducted between April 2012 and February 2014, in 602 adult outpatients (18-65 years) with moderate-to-severe MDD (Montgomery-Åsberg Depression Rating Scale (MADRS) ≥ 26), a major depressive episode of ≥ 3 months' duration, and self-reported cognitive symptoms were randomized to once-daily vortioxetine (10 or 20mg), duloxetine (60mg), or placebo for 8 weeks. Assessments included the University of California San Diego Performance-based Skills Assessment (UPSA) and the MADRS. Two versions of UPSA were utilized; UPSA ‒Validation of Intermediate Measures and UPSA Brief form. An aligned UPSA-B (communication and finance items) was examined for sensitivity analysis. Efficacy was analyzed versus placebo according to the dual response (change from baseline in UPSA ≥ 7 and ≥ 9 and reduction in MADRS total score from baseline ≥ 50%).

RESULTS: Significantly more vortioxetine-treated patients were classified as dual responders for change in MADRS total score and UPSA score of ≥ 7 (clinically important difference [CID]) (27.4% vs 14.5%; P = 0.004), and change above CID (≥ 9) (23.4% vs 13.9%; P = 0.025). Duloxetine did not differ significantly from placebo for these dual response criteria. Sensitivity analysis using the aligned UPSA-B confirmed these results for vortioxetine.

LIMITATIONS: An exploratory analysis of a new dual outcome measure in patients with MDD.

CONCLUSIONS: Vortioxetine, but not duloxetine, demonstrated a robust combined effect on depressive symptoms and functional capacity in patients with MDD.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01564862; European Clinical Trials Database [EudraCT] Number 2011-005298-22.