title: 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.
abstract: 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 Åsberg Depression Rating Scale (MADRS) single item (mixed-effects model for repeated measures; P<0.05) and most Hamilton Depression Rating Scale (HAMD17) single items. Significantly more levomilnacipran ER versus placebo patients (P < 0.05) achieved 'complete' (MADRS ≤ 5; 24 vs. 10%) and 'sustained' (MADRS ≤ 10 in Weeks 4-10; 16 vs. 10%) remission, Sheehan Disability Scale (SDS) response (total score ≤ 12 and each item score ≤ 4; 52 vs. 35%) and remission (total score ≤ 6 and each item score ≤ 2; 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 (MADRS ≥ 30). These results demonstrate the benefit of levomilnacipran ER over placebo for patients with symptomatic and functional impairment associated with major depressive disorder.
authors.affiliation: aImperial College School of Medicine, University of London, London, UK bPierre Fabre Medicament, Toulouse, France cPrescott Medical Communications Group, Chicago, Illinois dForest Research Institute, Jersey City, New Jersey, USA.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Montgomery
authors.forename: Lucilla
authors.initials: L
authors.lastname: Mansuy
authors.forename: Adam C
authors.initials: AC
authors.lastname: Ruth
authors.forename: Dayong
authors.initials: D
authors.lastname: Li
authors.forename: Carl
authors.initials: C
authors.lastname: Gommoll
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000627:therapeutic use*; D003521:Cyclopropanes / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003521:Cyclopropanes; D003692:Delayed-Action Preparations; D000078764:Milnacipran