Pharmacogenetics of Naltrexone and Disulfiram in Alcohol Dependent, Dually Diagnosed Veterans

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Abstract

Background:

Disulfiram and naltrexone were evaluated in treatment of individuals with co-occurring alcohol dependence and other Axis I disorders (e.g., Major Depression). We explored pharmacogenetic interactions in genotyped subjects.

Methods:

Alcohol dependent (AD) subjects received naltrexone alone, placebo alone, disulfiram with placebo or disulfiram with naltrexone. They were genotyped for OPRM1 rs1799971 (Asn40Asp), and DBH rs1611115 (C-1021T). N = 107 male European-American subjects were included.

Results:

There were no significant interactions with OPRM1. DBH interacted with naltrexone on the primary outcome of abstinence from heavy drinking (χ2(1) = 5.23, p = .02). “T” allele carriers on naltrexone had more abstinence compared to “CC” subjects on naltrexone (FET, p = .01). “T” allele carriers on naltrexone had the highest overall rates of abstinence from heavy drinking (>90%). Also, DBH genotype interacted with disulfram (F(1,17) = 7.52, p = .01) on drinks per drinking day with less drinking for subjects with the “CC” genotype than for T allele carriers on disulfiram.

Conclusions:

DBH*rs1611115*T associated with better response to naltrexone, while for those on disulfiram that drank, “CC” subjects drank less than T carriers. For rs1799971*G, we did not replicate findings from previous studies showing a more favorable response to NTX, possibly due to the small available sample.

Scientific Significance:

Genotyping rs1611115 may be useful in understanding inter-individual differences in AD treatment response.

Future Directions:

Further study of rs1611115 pharmacogenetics is warranted. (Am J Addict 2014;23:288–293)

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