Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators.
Acamprosate and naltrexone are effective medications in the treatment of alcoholism. However, effect sizes are modest. Pharmacogenomics may improve patient-treatment-matching and effect sizes. It is hypothesized that naltrexone exerts its effect through genetic characteristics associated with the dopaminergic/opioidergic positive reinforcement system, whereas acamprosate works through the glutamatergic/GABAergic negative reinforcement system. Alcohol-dependent subjects were randomly assigned to either acamprosate or naltrexone. Subjects participated in a cue-exposure experiment at the day before and at the last day of medication. Reductions in cue-induced craving and physiological cue reactivity were measured. Differential effects of naltrexone and acamprosate on these outcomes were tested for different polymorphisms of the opioid, dopamine, glutamate and GABA-receptors. Significant matching effects were found for polymorphisms at the DRD2, GABRA6 and GABRB2 gene. In addition, a trend was found for the OPRM1 polymorphism. This provides evidence for the matching potential of genotypes. It is expected that more effective treatments can be offered when genetic information is used in patient-treatment-matching.
Ooteman
Wendy
W
Amsterdam Institute for Addiction Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. w.ooteman@radiology.ucsf.edu
Naassila
Mickaël
M
Koeter
Maarten W J
MW
Verheul
Roel
R
Schippers
Gerard M
GM
Houchi
Hakim
H
Daoust
Martine
M
van den Brink
Wim
W
D000077443:Acamprosate; D000328:Adult; D000427:Alcohol Deterrents / Q000627:therapeutic use*; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology / Q000534:rehabilitation*; D003463:Cues; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009042:Motivation; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics; D013654:Taurine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D000427:Alcohol Deterrents; C546171:GABRA6 protein, human; C495710:GABRB2 protein, human; D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D017450:Receptors, Opioid, mu; D013654:Taurine; D009271:Naltrexone; D000077443:Acamprosate