Abstract
Separate investigations have suggested that olanzapine, a D4 antagonist, decreases craving after a priming dose of alcohol and that the DRD4 variable number of tandem repeats (VNTR) polymorphism influences the expression of craving after a priming dose of alcohol. The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving based on individual differences in DRD4 VNTR in a sample of heavy social drinkers. Participants were randomly assigned to receive olanzapine (5 mg) or a control medication (cyproheptadine, 4 mg) prior to consuming three alcoholic drinks. Participants completed subjective measures of craving and euphoria after each drink. Participants who were homozygous or heterozygous for the 7 (or longer) repeat allele of the DRD4 VNTR were classified as DRD4 L, while the other participants were classified as DRD4 S. The findings indicated that olanzapine reduces craving for alcohol at baseline for both DRD4 S and DRD4 L individuals, but only reduces craving after exposure to alcohol cues and after a priming dose of alcohol for DRD4 L individuals.
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Notes
This study was originally designed to include a third control medication (diphenhydramine, 25 mg). However, the diphenhydramine caused significantly greater sedation as compared to the olanzapine and cyproheptadine and was dropped from the study design. There were not enough DRD4 L individuals to include the diphenhydramine subjects in the analyses.
When the analyses were reconducted with the number of years of sustained drinking as a covariate, the Medication by DRD4 interaction effect sizes were all greater. We decided to present the main analyses without this covariate because it represents a more conservative perspective on the effects noted in the present study and simplifies the interpretation.
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Acknowledgements
This research was supported by grants from the National Institute on Alcoholism and Alcohol Abuse (R01AA11473) and the General Clinical Research Center Program of the National Center for Research Resources, National Institutes of Health (M01-RR00051).
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Hutchison, K., Wooden, A., Swift, R. et al. Olanzapine Reduces Craving for Alcohol: A DRD4 VNTR Polymorphism by Pharmacotherapy Interaction. Neuropsychopharmacol 28, 1882–1888 (2003). https://doi.org/10.1038/sj.npp.1300264
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DOI: https://doi.org/10.1038/sj.npp.1300264
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