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A Pharmacogenetic Approach To Treating Alcoholism

Serotonin (5-HT) is a chemical found naturally in the human brain. The serotonergic system is known to temper mood and emotion and is implicated in the control of many behavioral and physiological functions, including alcohol drinking. The serotonin transporter (5-HTT) is a protein that transports serotonin from synaptic spaces into the nerve cells that released it, which is one of the mechanisms for terminating serotonin’s action. Because serotonin is known to be a regulator of the severity of alcohol drinking, medications that affect the function of the 5-HTT seem promising. Ondansetron is one such drug.

Based on earlier genetic research on the serotonergic system, the authors of this paper hypothesized that genetic variants of the 5-HTT might lead to different individual reactions to the drug ondansetron. In other words, genotype might offer a clue to whether a drug like ondansetron would be useful in treating a specific type of alcoholism.

Participants in this study were 283 individuals seeking treatment for alcoholism. DNA was extracted from the blood of each patient. The patients were then randomly selected to receive either treatment (ondansetron twice daily) or placebo. All received cognitive behavioral therapy and underwent weekly assessments of their alcohol use.

The study found that drinkers with one particular genotype of the 5-HTT (designated LL) had a lower number of drinks per day and a higher percentage of days abstinent days than the other participants. The findings show that “ondansetron is a promising therapeutic agent for the treatment of severe drinking among alcohol-dependent individuals with the LL genotype.” When those with the LL genotype also possessed the TT genotype (another variant in the 3′-untranslated region of the 5-HTT), the effects were even greater for ondansetron to decrease severe drinking and promote abstinence. These findings present “a new pharmacogenetic approach using ondansetron to treat severe drinking and improve abstinence in alcoholics.”

(Johnson BA, Ait-Daoud N, Seneviratne C, Roache JD, Javors MA, Wang XQ, Liu L, Penberthy JK, DiClemente CC, Li MD: Pharmacogenetic approach at the serotonin transporter gene as a method of reducing the severity of alcohol drinking.  American Journal of Psychiatry, 2011, Jan 19. [Epub ahead of print]) (doi: 10.1176/appi.ajp.2010.10050755)

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