A Within-Group Design of Nontreatment Seeking 5-HTTLPR Genotyped Alcohol-Dependent Subjects Receiving Ondansetron and Sertraline

• Published in: Alcoholism, clinical and experimental research Vol. 33; no. 2; pp. 315 - 323
• Main Authors: Kenna, George A., Zywiak, William H., McGeary, John E., Leggio, Lorenzo, McGeary, Chinatsu, Wang, Shirley, Grenga, Andrea, Swift, Robert M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2009; Wiley
• Subjects: 5-HTTLPR; Addictive behaviors; Adult; Adult and adolescent clinical studies; Alcoholism; Alcoholism - genetics; Alcoholism - psychology; Alcoholism and acute alcohol poisoning; Biological and medical sciences; DNA - genetics; Early onset alcoholism; Female; Genotype; Genotypes; Humans; L/L; Late onset alcoholism; Male; Medical sciences; Middle Aged; Ondansetron; Ondansetron - therapeutic use; Patient Acceptance of Health Care - psychology; Psychiatric Status Rating Scales; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; S/L; S/S; Self Administration; Serotonin Antagonists - therapeutic use; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin Uptake Inhibitors - therapeutic use; Sertraline; Sertraline - therapeutic use; Socioeconomic Factors; Toxicology; Young Adult; Psychotropic; L/L; Reuptake inhibitor; Selective serotonin reuptake inhibitor; Design; Alcoholic beverage; S/L; Age of onset; S/S; Dependence; Antidepressant agent; Genotypes; Human; Late; Serotonin; 5-HTTLPR; Serotonin antagonist; Alcoholism; Late onset alcoholism; Genotype; Sertraline; Naphthylamine derivatives; 5-HT3 Serotonine receptor; Neurotransmitter; Early; Early onset alcoholism; Antiemetic; Ondansetron
• DOI: 10.1111/j.1530-0277.2008.00835.x
• ISSN: 0145-6008; 1530-0277

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.