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A randomized, double-blind, placebo-controlled trial of ondansetron for the treatment of cocaine use disorder with post hoc pharmacogenetic analysis.

Authors
  • Blevins, Derek1
  • Seneviratne, Chamindi2
  • Wang, Xin-Qun3
  • Johnson, Bankole A4
  • Ait-Daoud, Nassima5
  • 1 Department of Psychiatry, Columbia University Irving Medical Center/New York State Psychiatric Institute, New York, NY, United States. Electronic address: [email protected] , (United States)
  • 2 Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, United States. , (United States)
  • 3 Department of Public Health Sciences, University of Virginia, Charlottesville, VA, United States. , (United States)
  • 4 Department of Psychiatry & Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, United States (Former affiliation). , (United States)
  • 5 Department of Psychiatry & Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, United States. , (United States)
Type
Published Article
Journal
Drug and alcohol dependence
Publication Date
Sep 24, 2021
Volume
228
Pages
109074–109074
Identifiers
DOI: 10.1016/j.drugalcdep.2021.109074
PMID: 34600264
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Cocaine use disorder (CUD) has significant consequences and there remain no FDA-approved pharmacotherapies. Ondansetron is an indirect dopaminergic modulator that has shown efficacy in alcohol use disorder, particularly in phenotypic and genotypic subgroups, and was found to be efficacious in a pilot dose-finding trial for CUD. One-hundred eight (108) adults with CUD were randomized to ondansetron 4 mg twice daily or placebo for 9 weeks and assessed up to thrice weekly to evaluate self-reported cocaine use and urine benzoylecgonine. Participants received cognitive-behavioral therapy and brief behavioral compliance enhancement therapy. Consenting participants (N = 79) provided blood samples for exploratory pharmacogenetic analyses. Participants in both arms reduced cocaine use over time, but there was no statistically significant difference on percentage of cocaine-free days (PCFD; p = 0.972) or percentage of cocaine-free urine samples (PCFU; p = 0.909). Participants with early-onset CUD had greater improvement regardless of study arm (p = 0.002). Post hoc pharmacogenetic analyses demonstrated an interaction effect between treatment and rs1176713 SNP on PCFU in the total sample (p = 0.040) and African ancestry subset (p = 0.03). Constipation, fatigue, and somnolence were more common among ondansetron-treated participants (Fisher exact p < 0.05). Those who developed constipation were mostly rs1176713:GG carriers (Fisher exact p = 0.029). Ondansetron did not demonstrate efficacy in the treatment of CUD. However, these preliminary results suggest a genotype-based variance in response to ondansetron in African ancestry individuals with CUD. Further studies are needed to validate findings for developing a personalized genomic approach for CUD treatment in racially and ethnically diverse populations. Copyright © 2021 Elsevier B.V. All rights reserved.

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