Literature DB >> 31087723

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

June P Kampangkaew1,2, Catherine J Spellicy1,2, Ellen M Nielsen1,2, Mark J Harding1,2, An Ye1,2, Sara C Hamon3, Thomas R Kosten1,2, David A Nielsen1,2.   

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).
© 2019 American Academy of Addiction Psychiatry.

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Year:  2019        PMID: 31087723      PMCID: PMC6591035          DOI: 10.1111/ajad.12891

Source DB:  PubMed          Journal:  Am J Addict        ISSN: 1055-0496


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