Pharmacogenetics of naltrexone and disulfiram in alcohol dependent, dually diagnosed veterans.
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 (χ(2) (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.


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


CONCLUSIONS
Further study of rs1611115 pharmacogenetics is warranted.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System, West Haven, Connecticut.
Albert J
AJ
Arias
Joel
J
Gelernter
Ralitza
R
Gueorguieva
Elizabeth
E
Ralevski
Ismene L
IL
Petrakis
D000427:Alcohol Deterrents / Q000627:therapeutic use; D000437:Alcoholism / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D017831:Diagnosis, Dual (Psychiatry); D004221:Disulfiram / Q000627:therapeutic use*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D008875:Middle Aged; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics; D016896:Treatment Outcome; D014728:Veterans / Q000523:psychology*; D044465:White People / Q000235:genetics
D000427:Alcohol Deterrents; D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D004299:Dopamine beta-Hydroxylase; D004221:Disulfiram