Alcoholism Treatment Success May Hinge on Genes

The effectiveness of an experimental treatment for alcoholism depends on the genetic makeup of the people who receive it, according to a new study. The finding may help doctors personalize treatments for people who abuse alcohol.

The chemical messenger serotonin plays a vital role in helping brain cells communicate. It mediates many processes in the brain, including the rewarding effects of alcohol. The serotonin transporter protein binds serotonin in the space between brain cells and brings it back into the cell for reuse.

A team of researchers led by Dr. Bankole Johnson at the University of Virginia in Charlottesville previously showed that variations in the gene that encodes the serotonin transporter can significantly influence drinking intensity. Specifically, the LL and TT variants were associated with more severe drinking problems.

Johnson and his colleagues have also found that the medication ondansetron may be an effective therapy for some people with alcoholism. Ondansetron works by blocking receptors for the serotonin transporter. It is currently used to treat nausea and vomiting, often following chemotherapy.

In the new study, the researchers conducted a controlled trial to see whether serotonin transporter variants influence the effectiveness of ondansetron. They performed genetic analyses in alcohol-dependent people to determine which serotonin transporter gene variants were carried by each participant. The people were then randomly assigned to receive ondansetron or an inactive placebo. The study was supported by NIH’s National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute on Drug Abuse (NIDA). Results appeared on January 19, 2011, in the American Journal of Psychiatry.

When given ondansetron, participants with the LL variant had fewer drinks per day on average than those without the variant. They also had almost 10% more days without a drink. Participants who lacked the variant, however, showed no improvement with ondansetron.

Among people with the LL genotype, those receiving ondansetron had fewer drinks per day than those receiving placebo and over 11% more days without a drink. Ondansetron’s effects among those with the LL variant were even more pronounced when those people also carried the TT gene variant.

"By being able to do genetic screening beforehand, clinicians can eliminate a great deal of the trial and error approach to prescribing medicine," says Johnson. "Personalized medicine allows them to better predict a successful treatment option."

"This study represents an important milestone in the search for personalized treatments for alcohol dependence," says NIAAA Acting Director Dr. Kenneth R. Warren.