Pharmacogenetic role of dopamine transporter (SLC6A3) variation on response to disulfiram treatment for cocaine addiction

Am J Addict. 2019 Jul;28(4):311-317. doi: 10.1111/ajad.12891. Epub 2019 May 14.

Abstract

Background and objectives: Disulfiram has been beneficial in treating cocaine addiction in several studies. Patients with two SLC6A3 (DAT1) rs28363170 10-repeat alleles who have with genetically high dopamine transporter (DAT) levels may benefit from increased dopamine levels resulting from disulfiram treatment.

Methods: After stabilization for 2 weeks on methadone, 70 cocaine and opioid codependent patients were randomized into disulfiram and placebo groups for 12 weeks of treatment. We genotyped the SLC6A3 (DAT1) 40 bp 3'-untranslated region variable number tandem repeat variant and evaluated its role in moderating disulfiram efficacy for cocaine dependence.

Results: Among the 10,10-repeat genotype group, cocaine-positive urines dropped from 78% to 48% and from 80% to 75% among the 9-repeat carrier group in the disulfiram group (P = 0.0001, with an effect size of 0.09). No difference was observed in cocaine-positive urines in the placebo group between the 10,10-repeat genotype and the 9-allele carrier patients.

Conclusions and scientific significance: We found that patients with genetically higher DAT levels had better treatment outcomes with disulfiram pharmacotherapy of cocaine dependence than those with lower DAT levels. (Am J Addict 2019;28:311-317).

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaldehyde Dehydrogenase Inhibitors / therapeutic use*
  • Adult
  • Alleles
  • Biomarkers / metabolism
  • Cocaine-Related Disorders / drug therapy*
  • Cocaine-Related Disorders / genetics
  • Cocaine-Related Disorders / metabolism
  • Disulfiram / therapeutic use*
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Genetic Markers
  • Genotype
  • Humans
  • Male
  • Minisatellite Repeats*
  • Pharmacogenetics
  • Polymorphism, Genetic*
  • Treatment Outcome

Substances

  • Acetaldehyde Dehydrogenase Inhibitors
  • Biomarkers
  • Dopamine Plasma Membrane Transport Proteins
  • Genetic Markers
  • SLC6A3 protein, human
  • Disulfiram