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

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).

• Authors: June P Kampangkaew, Catherine J Spellicy, Ellen M Nielsen, Mark J Harding, An Ye, Sara C Hamon, Thomas R Kosten, David A Nielsen
• Journal: The American journal on addictions (Am J Addict) Vol. 28 Issue 4 Pg. 311-317 (07 2019) ISSN: 1521-0391 [Electronic] England
• PMID: 31087723 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 American Academy of Addiction Psychiatry.

Chemical References

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

Topics

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