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

• Published in: Journal of affective disorders Vol. 167; pp. 215 - 223
• Main Authors: Ball, Susan, Dellva, Mary Anne, D'Souza, Deborah N., Marangell, Lauren B., Russell, James M., Goldberger, Celine
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.10.2014; Elsevier
• Subjects: Adjunctive treatment; Adult; Adult and adolescent clinical studies; Antidepressive Agents - administration & dosage; Antidepressive Agents - therapeutic use; Biological and medical sciences; Biomarkers - metabolism; Depression; Depressive Disorder, Major - diagnosis; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - metabolism; Depressive Disorder, Major - psychology; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Edivoxetine; Efficacy; Humans; Major depressive disorder; Male; Medical sciences; Middle Aged; Miscellaneous; Mood disorders; Morpholines - administration & dosage; Morpholines - therapeutic use; Norepinephrine; Phenylethyl Alcohol - administration & dosage; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - therapeutic use; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Safety; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - therapeutic use; Sex Factors; Sexual Behavior - drug effects; Suicidal Ideation; Surveys and Questionnaires; Treatment Outcome; Efficacy; Norepinephrine; Edivoxetine; Safety; Major depressive disorder; Adjunctive treatment; Mood disorder; Human; Adjuvant treatment; Depression; Catecholamine; Selective serotonin reuptake inhibitor; Partial; Placebo; Neurotransmitter; Double blind study
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2014.06.006

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. Study design consisted of double-blind, 10-week therapy of adjunctive edivoxetine (6–18mg 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. 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. Study was underpowered for an alpha 2-sided 0.05 significance level for the primary outcome. 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.