Format

Send to

Choose Destination
See comment in PubMed Commons below
Alcohol Clin Exp Res. 2009 Feb;33(2):315-23. doi: 10.1111/j.1530-0277.2008.00835.x. Epub 2008 Nov 19.

A within-group design of nontreatment seeking 5-HTTLPR genotyped alcohol-dependent subjects receiving ondansetron and sertraline.

Author information

1
Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, RI 02908, USA. George_Kenna@Brown.edu

Abstract

BACKGROUND:

Serotonergic mechanisms are associated with the development of alcohol dependence (AD), however, studies evaluating serotonergic medications have produced conflicting results. One hypothesis suggests that differential response may be due to a functional polymorphism of the 5-HTTLPR promoter region of the serotonin re-uptake transporter (5-HTT). The L/L genotype is postulated to be associated with early onset alcoholism and the S/S or S/L genotypes associated with late onset alcoholism. The aim of this study was to match and mismatch L/L, S/S, or S/L genotypes with administration of ondansetron and sertraline.

METHODS:

Fifteen nontreatment seeking alcohol-dependent individuals were randomized to 1 of 2 counterbalanced arms to receive either 200 mg/d of sertraline or ondansetron 0.5 mg/d for 3 weeks followed by an alcohol self-administration experiment (ASAE), then received placebo for 3 weeks followed by a second ASAE. Participants then received the alternate drug for 2 weeks followed by a third ASAE.

RESULTS:

At the first ASAE compared to sertraline, ondansetron significantly improved drinking outcomes for the L/L genotype for the ASAE volume consumed (100% reduction based on between-subjects comparison, t = 2.35), and for drinks per drinking day during the 7 days prior to the ASAE (79% reduction and t = 4.34). Compared with ondansetron for S/S or S/L genotypes, outcomes at ASAE 1 for sertraline and S/S or S/L genotypes are opposite than hypothesized. Overall, subjects reduced drinking across their participation in the trial, as there appears to be an order effect.

CONCLUSION:

This study suggests that ondansetron may reduce alcohol consumption in alcohol-dependent individuals who have the L/L genotype as measured naturalistically and during the ASAE. By contrast there was no support that sertraline reduces alcohol use in individuals who have S/S or S/L genotypes. Evidence in the literature suggests that AD in some individuals may be influenced by a gene by socio-environmental interaction making pharmacological treatment with serotonergic drugs complex. Research must consider that typologies may predict successful treatment of AD in future trials.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center