title: Evaluation of functional health and well-being in patients receiving levomilnacipran ER for the treatment of major depressive disorder.
abstract: BACKGROUND
  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 III, 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-Åsberg 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 [2.44; P = 0.0010], Vitality [2.48; P = 0.0307], Social Functioning [3.25; 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.
  
  
  CONCLUSIONS
  The trial was limited by short duration; analyses were post hoc and adjustments were not made for multiplicity.
  
  
  CONCLUSIONS
  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.
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Steven I
authors.initials: SI
authors.lastname: Blum
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA. Electronic address: stavros.tourkodimitris@frx.com.
authors.forename: Stavros
authors.initials: S
authors.lastname: Tourkodimitris
authors.affiliation: Prescott Medical Communications Group, Chicago, IL, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Ruth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D003521:Cyclopropanes / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology*; D004311:Double-Blind Method; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008603:Mental Health; D008875:Middle Aged; D000078764:Milnacipran; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012919:Social Behavior; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D003521:Cyclopropanes; D003692:Delayed-Action Preparations; D000078764:Milnacipran
keywords: Health outcomes; Levomilnacipran ER; Major depressive disorder; SF-36; Serotonin and norepinephrine reuptake inhibitor