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Am J Psychiatry. 2011 Mar;168(3):265-75. doi: 10.1176/appi.ajp.2010.10050755. Epub 2011 Jan 19.

Pharmacogenetic approach at the serotonin transporter gene as a method of reducing the severity of alcohol drinking.

Author information

1
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22908-0623, USA. bankolejohnson@virginia.edu

Erratum in

  • Am J Psychiatry. 2011 Jul;168(7):756.

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-HT(3) 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.

Comment in

PMID:
21247998
PMCID:
PMC3063997
DOI:
10.1176/appi.ajp.2010.10050755
[Indexed for MEDLINE]
Free PMC Article

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