The efficacy of extended-release levomilnacipran in moderate to severe major depressive disorder: secondary and post-hoc analyses from a randomized, double-blind, placebo-controlled study

Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin and norepinephrine reuptake inhibitor that is Food and Drug Administration approved for once-daily treatment of major depressive disorder in adults. Secondary and post-hoc analyses were carried out on data from a positive 10-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter, proof-of-concept trial (EudraCT Number: 2006-002404-34) on 75 or 100 mg/day levomilnacipran extended release (ER). Included outpatients (18-70 years) met the criteria for a major depressive episode. There was a statistically significant difference in favor of levomilnacipran ER versus placebo in change from baseline to week 10 on every Montgomery angstrom sberg Depression Rating Scale (MADRS) single item (mixed-effects model for repeated measures; P<0.05) and most Hamilton Depression Rating Scale (HAMD(17)) single items. Significantly more levomilnacipran ER versus placebo patients (P<0.05) achieved complete' (MADRS5; 24 vs. 10%) and sustained' (MADRS10 in Weeks 4-10; 16 vs. 10%) remission, Sheehan Disability Scale (SDS) response (total score12 and each item score4; 52 vs. 35%) and remission (total score6 and each item score2; 26 vs. 17%), and combined symptomatic (MADRS) and functional (SDS) remission (19 vs. 8%). Treatment effects of similar magnitude were observed in the severe depression subgroup (MADRS30). These results demonstrate the benefit of levomilnacipran ER over placebo for patients with symptomatic and functional impairment associated with major depressive disorder. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.