Double-blind, placebo-controlled, proof-of-concept trial of a kappa-selective opioid receptor antagonist augmentation in treatment-resistant depression.

Abstract

BACKGROUND:

Kappa-opioid antagonism may possess antidepressant properties. We assessed, in a proof-of-concept pilot trial among patients with major depressive disorder with inadequate response to antidepressants, the efficacy of adjunctive CERC-501 (formerly LY2456302), a kappaselective opioid receptor antagonist.

METHODS:

In a Sequential Parallel Comparison Design study, patients were pre-randomized to: a) 10 mg/d of CERC-501 for 6 days, b) 20 mg/d of CERC-501 for 6 days, c) placebo for 3 days followed by 10 mg/d of CERC- 501 for 3 days, d) placebo for 3 days followed by 20 mg/d of CERC-501 for 3 days, or e) placebo for 6 days.

RESULTS:

The study was terminated early by the National Institute of Mental Health due to slow enrollment (N = 8). The weighted mean difference of changes (drug vs placebo) in the 6-item Hamilton Depression Rating Scale (HAMD-6) (primary outcome measure) (1.28), Montgomery-Åsberg Depression Rating Scale (MADRS) (2.33), Perceived Stress Scale (1.01), Symptoms of Depression Questionnaire (9.17), Positive Affect Scale (PAS) (6.39), Symptom Questionnaire (SQ) Depression scale (2.94), SQ Anger- Hostility scale (1.67), and Patient-Reported Outcomes Measurement Information System Satisfaction with Participation in Discretionary Social Activities (4.67) scores were all numerically but not statistically greater for CERC-501 than for placebo.

CONCLUSIONS:

Although the small sample size limits the ability to draw conclusions, results suggest that CERC-501 may have antidepressant effects. Additional studies are necessary to further explore these effects of CERC-501.

• Authors: Maurizio Fava, Erica Mazzone, Marlene Freeman, Martina Flynn, Heidi Judge, Bettina Hoeppner, Rebecca S Hock, Amy Shui, Matthew Macaluso, Mary F Morrison, Linda L Carpenter, Richard Shelton, John Zajecka, George I Papakostas
• Journal: Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists (Ann Clin Psychiatry) Vol. 32 Issue 4 Pg. 18-26 (02 2020) ISSN: 1547-3325 [Electronic] United States
• PMID: 33125454 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Benzamides
• Narcotic Antagonists
• Pyrrolidines
• Receptors, Opioid, kappa
• Aticaprant

Topics

• Benzamides (therapeutic use)
• Depressive Disorder, Treatment-Resistant (drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Narcotic Antagonists (therapeutic use)
• Psychiatric Status Rating Scales (statistics & numerical data)
• Pyrrolidines (therapeutic use)
• Receptors, Opioid, kappa
• Treatment Outcome