title: Efficacy outcomes from 3 clinical trials of edivoxetine as adjunctive treatment for patients with major depressive disorder who are partial responders to selective serotonin reuptake inhibitor treatment.
abstract: OBJECTIVE
  Three studies examined whether edivoxetine (a highly selective norepinephrine reuptake inhibitor) had efficacy as adjunctive therapy for patients with major depressive disorder (DSM-IV-TR) who were partial responders to selective serotonin reuptake inhibitor (SSRI) treatment of at least 6 weeks' duration.
  
  
  METHODS
  Studies were 8-week randomized, placebo-controlled trials with a 3-week double-blind placebo lead-in phase, conducted from December 16, 2010, to October 21, 2013. Patients entered the double-blind adjunctive treatment phase if they met randomization criteria (< 25% improvement on Montgomery-Asberg Depression Rating Scale [MADRS] and MADRS total score ≥ 14); patients not randomized remained on adjunctive placebo. Study 1 compared fixed-dose edivoxetine (12 or 18 mg daily) + SSRI (N = 231 and N = 230, respectively) with placebo + SSRI (N = 240); study 2 compared flexible-dose edivoxetine (12-18 mg daily) + SSRI (N = 232) and fixed-dose edivoxetine (6 mg daily) + SSRI (N = 226) with placebo + SSRI (N = 231); and study 3 compared flexible-dose edivoxetine (12-18 mg daily) + SSRI (N = 230) with placebo + SSRI (N = 219). The primary outcome was mean change from randomization baseline to week 8 in MADRS total score, analyzed using repeated measures analysis.
  
  
  RESULTS
  Each trial failed to meet the primary and most of the secondary objectives. The least-squares mean changes in MADRS total score were as follows-study 1: -8.5 (edivoxetine 12 mg + SSRI), -8.7 (edivoxetine 18 mg + SSRI), and -7.8 (placebo + SSRI); study 2: -9.4 (edivoxetine 12-18 mg + SSRI), -9.6 (edivoxetine 6 mg + SSRI), and -9.4 (placebo + SSRI); and study 3: -8.7 (edivoxetine 12-18 mg + SSRI) and -8.5 (placebo + SSRI).
  
  
  CONCLUSIONS
  Adjunctive edivoxetine treatment for patients with major depressive disorder who were partial responders to SSRIs did not significantly improve efficacy outcomes.
  
  
  BACKGROUND
  ClinicalTrials.gov identifiers: NCT01173601, NCT01187407, NCT01185340.
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285 ball_susan_G@lilly.com.
authors.forename: Susan G
authors.initials: SG
authors.lastname: Ball
authors.forename: Margaret B
authors.initials: MB
authors.lastname: Ferguson
authors.forename: James M
authors.initials: JM
authors.lastname: Martinez
authors.forename: Beth A
authors.initials: BA
authors.lastname: Pangallo
authors.forename: E Serap Monkul
authors.initials: ES
authors.lastname: Nery
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Dellva
authors.forename: JonDavid
authors.initials: J
authors.lastname: Sparks
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Mark
authors.initials: M
authors.lastname: Bangs
authors.forename: Celine
authors.initials: C
authors.lastname: Goldberger
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D061218:Depressive Disorder, Treatment-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors