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CLINICAL STUDY: Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators

Authors

  • Wendy Ooteman,

    Corresponding author
    1. Amsterdam Institute for Addiction Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands,
    2. University of California San Francisco, School of Medicine, Department of Radiology and Biomedical Imaging, Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center San Francisco, USA,
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  • Mickaël Naassila,

    1. University of Picardie Jules Verne, Faculte de Pharmacie, INSERM ERI 24, Research Group on Alcohol and Pharmacodependences (GRAP), Amiens, France,
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  • Maarten W. J. Koeter,

    1. Amsterdam Institute for Addiction Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands,
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  • Roel Verheul,

    1. Viersprong Institute for Studies on Personality Disorders, Halsteren, the Netherlands,
    2. Department of Clinical Psychology, University of Amsterdam, Amsterdam, the Netherlands
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  • Gerard M. Schippers,

    1. Amsterdam Institute for Addiction Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands,
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  • Hakim Houchi,

    1. University of Picardie Jules Verne, Faculte de Pharmacie, INSERM ERI 24, Research Group on Alcohol and Pharmacodependences (GRAP), Amiens, France,
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  • Martine Daoust,

    1. University of Picardie Jules Verne, Faculte de Pharmacie, INSERM ERI 24, Research Group on Alcohol and Pharmacodependences (GRAP), Amiens, France,
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  • Wim Van Den Brink

    1. Amsterdam Institute for Addiction Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands,
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Wendy Ooteman, Center San Francisco, 4150 Clement Street #114M, San Francisco, CA 94121, USA. E-mail: w.ooteman@radiology.ucsf.edu; CC: w.vandenbrink@amc.uva.nl

ABSTRACT

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.

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