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

J Clin Psychiatry. 2016 May;77(5):635-42. doi: 10.4088/JCP.14m09619.

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.

Method: 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.

Trials registrations: ClinicalTrials.gov identifiers: NCT01173601, NCT01187407, NCT01185340.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Depressive Disorder, Treatment-Resistant / diagnosis
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Depressive Disorder, Treatment-Resistant / psychology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Serotonin Uptake Inhibitors

Associated data

  • ClinicalTrials.gov/NCT01173601
  • ClinicalTrials.gov/NCT01187407
  • ClinicalTrials.gov/NCT01185340