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Abstract

Objective:

Severe drinking can cause serious morbidity and death. Because the serotonin transporter (5-HTT) is an important regulator of neuronal 5-HT function, allelic differences at that gene may modulate the severity of alcohol consumption and predict therapeutic response to the 5-HT3 receptor antagonist, ondansetron.

Method:

The authors randomized 283 alcoholics by genotype in the 5′-regulatory region of the 5-HTT gene (LL/LS/SS), with additional genotyping for another functional single-nucleotide polymorphism (T/G), rs1042173, in the 3′-untranslated region, in a double-blind controlled trial. Participants received either ondansetron (4 μg/kg twice daily) or placebo for 11 weeks, plus standardized cognitive-behavioral therapy.

Results:

Individuals with the LL genotype who received ondansetron had a lower mean number of drinks per drinking day (−1.62) and a higher percentage of days abstinent (11.27%) than those who received placebo. Among ondansetron recipients, the number of drinks per drinking day was lower (−1.53) and the percentage of days abstinent higher (9.73%) in LL compared with LS/SS individuals. LL individuals in the ondansetron group also had a lower number of drinks per drinking day (−1.45) and a higher percentage of days abstinent (9.65%) than all other genotype and treatment groups combined. For both number of drinks per drinking day and percentage of days abstinent, 5′-HTTLPR and rs1042173 variants interacted significantly. LL/TT individuals in the ondansetron group had a lower number of drinks per drinking day (−2.63) and a higher percentage of days abstinent (16.99%) than all other genotype and treatment groups combined.

Conclusions:

The authors propose a new pharmacogenetic approach using ondansetron to treat severe drinking and improve abstinence in alcoholics.

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Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 265 - 275
PubMed: 21247998

History

Received: 24 May 2010
Revision received: 14 August 2010
Revision received: 6 October 2010
Accepted: 15 October 2010
Published online: 1 March 2011
Published in print: March 2011

Authors

Details

Bankole A. Johnson, D.Sc., M.D.
From the Departments of Psychiatry and Neurobehavioral Sciences and Public Health Sciences, University of Virginia, Charlottesville; the Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Tex.; the Department of Psychology, University of Maryland, Baltimore County, Baltimore, Md.
Nassima Ait-Daoud, M.D.
From the Departments of Psychiatry and Neurobehavioral Sciences and Public Health Sciences, University of Virginia, Charlottesville; the Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Tex.; the Department of Psychology, University of Maryland, Baltimore County, Baltimore, Md.
Chamindi Seneviratne, M.D.
From the Departments of Psychiatry and Neurobehavioral Sciences and Public Health Sciences, University of Virginia, Charlottesville; the Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Tex.; the Department of Psychology, University of Maryland, Baltimore County, Baltimore, Md.
John D. Roache, Ph.D.
From the Departments of Psychiatry and Neurobehavioral Sciences and Public Health Sciences, University of Virginia, Charlottesville; the Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Tex.; the Department of Psychology, University of Maryland, Baltimore County, Baltimore, Md.
Martin A. Javors, Ph.D.
From the Departments of Psychiatry and Neurobehavioral Sciences and Public Health Sciences, University of Virginia, Charlottesville; the Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Tex.; the Department of Psychology, University of Maryland, Baltimore County, Baltimore, Md.
Xin-Qun Wang, M.S.
From the Departments of Psychiatry and Neurobehavioral Sciences and Public Health Sciences, University of Virginia, Charlottesville; the Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Tex.; the Department of Psychology, University of Maryland, Baltimore County, Baltimore, Md.
Lei Liu, Ph.D.
From the Departments of Psychiatry and Neurobehavioral Sciences and Public Health Sciences, University of Virginia, Charlottesville; the Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Tex.; the Department of Psychology, University of Maryland, Baltimore County, Baltimore, Md.
J. Kim Penberthy, Ph.D.
From the Departments of Psychiatry and Neurobehavioral Sciences and Public Health Sciences, University of Virginia, Charlottesville; the Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Tex.; the Department of Psychology, University of Maryland, Baltimore County, Baltimore, Md.
Carlo C. DiClemente, Ph.D.
From the Departments of Psychiatry and Neurobehavioral Sciences and Public Health Sciences, University of Virginia, Charlottesville; the Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Tex.; the Department of Psychology, University of Maryland, Baltimore County, Baltimore, Md.
Ming D. Li, Ph.D.
From the Departments of Psychiatry and Neurobehavioral Sciences and Public Health Sciences, University of Virginia, Charlottesville; the Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Tex.; the Department of Psychology, University of Maryland, Baltimore County, Baltimore, Md.

Notes

Address correspondence and reprint requests to Dr. Johnson, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, P.O. Box 800623, Charlottesville, VA 22908-0623; [email protected] (e-mail).

Funding Information

The other authors report no financial relationships with commercial interests.

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