title: A double-blind, placebo-controlled study of edivoxetine as an adjunctive treatment for patients with major depressive disorder who are partial responders to selective serotonin reuptake inhibitor treatment.
abstract: BACKGROUND
  This phase 2 study examined the efficacy and tolerability of edivoxetine, a highly selective norepinephrine reuptake inhibitor, as an adjunctive treatment for patients with major depressive disorder (MDD) who have a partial response to selective serotonin reuptake inhibitor (SSRI) treatment.
  
  
  METHODS
  Study design consisted of double-blind, 10-week therapy of adjunctive edivoxetine (6-18 mg once daily) or adjunctive placebo with SSRI. Inclusion/entry criteria included partial response to current SSRI by investigator opinion and a GRID 17-item Hamilton Rating Scale for Depression (HAMD17) total score ≥16. The primary efficacy measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Safety measures included treatment-emergent adverse events (TEAE) and vital signs.
  
  
  RESULTS
  For the primary evaluable population (n=63 for adjunctive edivoxetine and n=68 for adjunctive placebo), the treatment groups did not differ significantly on the primary outcome of change from baseline to week 8 in the MADRS total score; the effect size of edivoxetine treatment was 0.26. Significant treatment differences, favoring adjunctive edivoxetine (p≤.05), were shown for improvements in role functioning and the functional impact of fatigue. For the adjunctive edivoxetine randomized group (N=111), the most frequent TEAEs were hyperhidrosis (7.2%), nausea (7.2%), erectile dysfunction (6.3%) and testicular pain (6.3%). Hemodynamic changes were observed in blood pressure and pulse rate between treatment groups.
  
  
  CONCLUSIONS
  Study was underpowered for an alpha 2-sided 0.05 significance level for the primary outcome.
  
  
  CONCLUSIONS
  For patients with MDD who had a partial response to SSRIs, adjunctive edivoxetine treatment was not statistically superior to adjunctive placebo on the primary outcome measure. However, pending further study, improved functioning and remission rate suggest a potential role for edivoxetine for patients with depression.
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, United States; Indiana University School of Medicine, Department of Psychiatry, Indianapolis, IN, 46202, United States. Electronic address: ball_susan_g@lilly.com.
authors.forename: Susan
authors.initials: S
authors.lastname: Ball
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, United States.
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Dellva
authors.affiliation: InVentiv Health Clinical, Ann Arbor, MI 48108, United States.
authors.forename: Deborah N
authors.initials: DN
authors.lastname: D'Souza
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, United States; The University of Texas Health Science Center, Houston, TX 77030, United States.
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Marangell
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, United States.
authors.forename: James M
authors.initials: JM
authors.lastname: Russell
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, United States.
authors.forename: Celine
authors.initials: C
authors.lastname: Goldberger
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012737:Sex Factors; D012725:Sexual Behavior / Q000187:drug effects; D059020:Suicidal Ideation; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D009025:Morpholines; D010626:Phenylethyl Alcohol; D017367:Selective Serotonin Reuptake Inhibitors; C568831:alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanol
keywords: Adjunctive treatment; Edivoxetine; Efficacy; Major depressive disorder; Norepinephrine; Safety