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. 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.