In the past 12 years, we have learned that: a) ondansetron, a serotonin-3 receptor antagonist, is efficacious treatment for alcohol dependence among alcohol-dependent adults who develop problem drinking before the age of 25 years (i.e., early-onset alcoholics);b) alcohol-dependent adolescents reduce their drinking markedly following ondansetron treatment, and c) alcoholics who are homozygous for the long polymorphic form (LL) of the serotonin transporter (5-HTT) allele experience greater reduction in severe drinking following ondansetron treatment than those who are homozygous for the short form (SS) or heterozygous for the long form (SL) of the 5-HTT allele. Ondansetron is, therefore, suited uniquely to enhancing current treatment approaches for severe or binge drinking among emerging (18- to 25-year-old) adults, especially those with the LL genotype. Whilst the mainstay of individual-focused interventions for emerging adults has been to provide brief motivational interventions such as the BASICS program to increase awareness of drinking consequences and readiness for change for reducing severe or binge drinking, many participants do not progress to the action phase of readiness to quit and continue to drink at hazardous levels. We, therefore, plan to apply what we have learned over the last 12 years to test the hypothesis that ondansetron plus our adapted version of BASICS (BASICS Plus) will be more efficacious than BASICS Plus alone at reducing severe or binge drinking, especially among emerging adults with the LL genotype. We also shall test the additional hypothesis that ondansetron adds to the therapeutic benefit of BASICS Plus even in those with lower readiness for change. The study design will be a randomized, double-blind, placebo-controlled trial in which emerging adults will receive 1 week of single-blind placebo followed by 8 weeks of ondansetron + BASICS Plus or 1 week of single-blind placebo followed by 8 weeks of placebo + BASICS Plus. Each treatment group shall contain 150 individuals (total N=300), stratified into two equal subgroups of those who are LL vs. Sx (i.e., LS or SS) for the 5-HTT allele. This innovative and significant study is designed to develop an efficacious pharmacotherapeutic and pharmacogenetic approach that can enhance the efficacy of a brief intervention to treat severe drinking in emerging adults.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA010522-17
Application #
8269152
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Roach, Deidra
Project Start
1995-04-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
17
Fiscal Year
2012
Total Cost
$663,655
Indirect Cost
$218,341
Name
University of Virginia
Department
Psychiatry
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Johnson, Bankole A; Seneviratne, Chamindi; Wang, Xin-Qun et al. (2013) Determination of genotype combinations that can predict the outcome of the treatment of alcohol dependence using the 5-HT(3) antagonist ondansetron. Am J Psychiatry 170:1020-31
Seneviratne, Chamindi; Franklin, Jason; Beckett, Katherine et al. (2013) Association, interaction, and replication analysis of genes encoding serotonin transporter and 5-HT3 receptor subunits A and B in alcohol dependence. Hum Genet 132:1165-76
Vaughan, Michelle D; Hook, Joshua N; Wagley, J Nile et al. (2012) Changes in Affect and Drinking Outcomes in a Pharmacobehavioral Trial for Alcohol Dependence. Addict Disord Their Treat 11:14-25
Johnson, Bankole A; Messing, Robert O; Charness, Michael E et al. (2011) Should the reorganization of addiction-related research across all the National Institutes of Health be structural?--The devil is truly in the details. Alcohol Clin Exp Res 35:572-80
Johnson, Bankole A; Ait-Daoud, Nassima; Seneviratne, Chamindi et al. (2011) Pharmacogenetic approach at the serotonin transporter gene as a method of reducing the severity of alcohol drinking. Am J Psychiatry 168:265-75
Johnson, Bankole A; Ait-Daoud, Nassima (2010) Topiramate in the new generation of drugs: efficacy in the treatment of alcoholic patients. Curr Pharm Des 16:2103-12
Johnson, Bankole A (2010) Medication treatment of different types of alcoholism. Am J Psychiatry 167:630-9
Ait-Daoud, Nassima; Roache, John D; Dawes, Michael A et al. (2009) Can serotonin transporter genotype predict craving in alcoholism? Alcohol Clin Exp Res 33:1329-35
Seneviratne, Chamindi; Huang, Weihua; Ait-Daoud, Nassima et al. (2009) Characterization of a functional polymorphism in the 3'UTR of SLC6A4 and its association with drinking intensity. Alcohol Clin Exp Res 33:332-9
Seneviratne, Chamindi; Ait-Daoud, Nassima; Ma, Jennie Z et al. (2009) Susceptibility locus in neurokinin-1 receptor gene associated with alcohol dependence. Neuropsychopharmacology 34:2442-9

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