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


CONCLUSIONS
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.
Kenna
George A
GA
Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, RI 02908, USA. George_Kenna@Brown.edu
Zywiak
William H
WH
McGeary
John E
JE
Leggio
Lorenzo
L
McGeary
Chinatsu
C
Wang
Shirley
S
Grenga
Andrea
A
Swift
Robert M
RM
D000328:Adult; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology*; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017294:Ondansetron / Q000627:therapeutic use*; D010342:Patient Acceptance of Health Care / Q000523:psychology*; D011569:Psychiatric Status Rating Scales; D012646:Self Administration; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use*; D012959:Socioeconomic Factors; D055815:Young Adult
D004247:DNA; D017294:Ondansetron; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C493230:SLC6A4 protein, human