Evaluation of functional health and well-being in patients receiving levomilnacipran ER for the treatment of major depressive disorder

Introduction: Levomilnacipran extended-release (ER) is an FDA-approved serotonin norepinephrine reuptake inhibitor (SNRI) for treating major depressive disorder (MDD). SF-36v2 Health Survey outcomes from a Phase Ill, randomized, double-blind, placebo-controlled study (NCT00969709) were evaluated. Methods: Prospective and post hoc analyses of SF-36 Mental and Physical Component Summaries (MCS, PCS), and individual domains compared pooled levomilnacipran ER doses (40, 80, 120 mg/day) with placebo. Patients (18-65 years) had MDD, depressive episode >= 8 weeks, and Montgomery-Asberg Depression Rating Scale total score >= 30. SF-36 score changes from baseline to Week 8 were analyzed using ANCOVA and the observed cases approach (Intent-to-Treat [ITT] Population). Minimally important differences (MID) evaluated clinical relevance. Results: Baseline MCS scores reflected marked mental deficits in the ITT Population (levomilnacipran ER=529; placebo = 175). MCS change at Week 8 was significantly greater for levomilnacipran ER than placebo (LSMD [SE]=4.8 [1.5]; P=0.0011); MID exceeded the 3-point threshold. Baseline PCS scores suggested minimal physical deficits; no between-group difference at Week 8 was noted. LSMD was nominally statistically significant (P < 0.05) for levomilnacipran ER versus placebo in 5 domains (General Health [244; P=0.0010], Vitality [2.48; P=0.0307], Social Functioning [325; P=0.0097], Role Emotional [3.38; P=0.0078], Mental Health [4.34; P=0.0005]); changes in Vitality, Social Functioning, and Mental Health exceeded MID. Limitations: The trial was limited by short duration; analyses were post hoc and adjustments were not made for multiplicity. Conclusion: Statistically significant and clinically meaningful improvement on the MCS and several individual domains suggest overall and dimensional improvement in health related functioning for patients with MDD treated with levomilnacipran ER versus placebo. (C) 2014 The Authors. Published by Elsevier B.V.