Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial

Pierre Tran, Phil Skolnick, P. Czobor, N. Y. Huang, Mark Bradshaw, Anthony McKinney, Maurizio Fava

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Amitifadine (EB-1010, formerly DOV 21,947) is a serotonin-preferring triple reuptake inhibitor with a relative potency to inhibit serotonin, norepinephrine, and dopamine uptake of ∼1:2:8, respectively. This 6-week, multicenter, randomized, double-blind, parallel, placebo-controlled study evaluated the efficacy and tolerability of amitifadine in 63 patients with major depressive disorder. Eligible patients (17-item Hamilton Depression Rating Scale [HAMD-17] ≥ 22 at baseline) were randomized to amitifadine 25 mg twice daily (BID) for 2 weeks, then 50 mg BID for 4 weeks or placebo. Mean baseline scores in the modified intent-to-treat population (n = 56) were 31.4 for the Montgomery-åsberg Depression Rating Scale (MADRS), 29.6 for the HAMD-17, and 25.4 for the Derogatis Interview for Sexual Functioning - Self Report (DISF-SR). At the end of the 6-week double-blind treatment, estimated least squares mean change from baseline (mixed-model repeated measures [MMRM]) in MADRS total score was statistically significantly superior for amitifadine compared to placebo (18.2 vs. 22.0; p = 0.028), with an overall statistical effect size of -0.601 (Cohen's d). Amitifadine also was statistically significantly superior to placebo (p = 0.03) for the Clinical Global Impression of Change - Improvement. An anhedonia factor score grouping of MADRS Items 1 (apparent sadness), 2 (reported sadness), 6 (concentration difficulties), 7 (lassitude), and 8 (inability to feel) demonstrated a statistically significant difference in favor of amitifadine compared to placebo (p = 0.049). No differences were observed between treatments in DISF-SR scores. Amitifadine was well-tolerated. Two patients on each treatment discontinued the study early due to adverse events; however, no serious adverse events were reported. This initial clinical trial in patients with severe major depression demonstrated significant antidepressant activity with amitifadine, including attenuating symptoms of anhedonia, and a tolerability profile that was comparable to placebo. The efficacy and tolerability of amitifadine for major depressive disorder are being investigated in additional clinical trials.

Original languageEnglish
Pages (from-to)64-71
Number of pages8
JournalJournal of Psychiatric Research
Volume46
Issue number1
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Major Depressive Disorder
Placebos
Therapeutics
Anhedonia
Depression
Self Report
Serotonin
1-(3,4-dichlorophenyl)-3-azabicyclo-(3.1.0)hexane hydrochloride
Controlled
Efficacy
Placebo
Clinical Trials
Interviews
Least-Squares Analysis
Antidepressive Agents
Fatigue
Dopamine
Norepinephrine

Keywords

  • Amitifadine
  • Anhedonia
  • Major depressive disorder
  • Sexual function
  • Triple reuptake inhibitor
  • Weight

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Arts and Humanities (miscellaneous)

Cite this

Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder : A randomized, double-blind, placebo-controlled trial. / Tran, Pierre; Skolnick, Phil; Czobor, P.; Huang, N. Y.; Bradshaw, Mark; McKinney, Anthony; Fava, Maurizio.

In: Journal of Psychiatric Research, Vol. 46, No. 1, 01.2012, p. 64-71.

Research output: Contribution to journalArticle

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