Genetically Targeted Medication Shows Great Promise in Treating Alcohol Addiction, Landmark U.Va. Study Finds

Listen to the UVA Today Radio Show report on this story by Jane Ford:

January 19, 2011 — For the first time in alcohol addiction research, University of Virginia investigators have successfully treated alcohol-dependent individuals with medication that is tailored specifically to match their genetic profile.

"Our findings suggest a new paradigm for the treatment of alcoholism, as well as a major breakthrough in individualized medicine for predetermined genotypes," said Dr. Bankole Johnson, the study's leader and professor and chair of the U.Va. Department of Psychiatry and Neurobehavioral Sciences.

The study, to be published in the March issue of the American Journal of Psychiatry and now available online, tested 283 genetically profiled alcoholics for the efficacy of ondansetron, a serotonin antagonist drug.

Previous research by U.Va. scientists has found that specified variations in the serotonin transporter gene SLC6A4 play a significant role in influencing drinking intensity. Furthermore, past U.Va. research has identified ondansetron as a likely pharmaceutical target for serotonin-related genes.

Serotonin is a brain chemical that is involved in the regulation of pain perception, sleep, mood and other psychological processes. Studies have shown that serotonin mediates the rewarding effects of alcohol.

In this latest study, U.Va. researchers randomized alcoholics by certain genotypes in a controlled, double-blind clinical trial. Subjects received either ondansetron or placebo for 11 weeks, and all received standard cognitive behavioral therapy. A majority of subjects were white males, and more than 65 percent of subjects completed the study in its entirety. The study was funded by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.

Study findings show that ondansetron is indeed a promising therapeutic agent for the treatment of severe alcohol consumption among alcohol-dependent individuals with the predicted genetic marker – a marker that's responsible for the amount of pleasure certain people may perceive while drinking or may perceive as a craving when they stop drinking, Johnson explained.

"The treatment response among those who received ondansetron was remarkable," Johnson said. "What this tells us is that we have measurable evidence that personalized medicine is indeed a viable treatment for alcohol dependence."

The primary outcome tested by researchers involved ondansetron's effects on the severity of alcohol consumption in selected alcohol-dependent individuals. The study was confined to one secondary variable – the percentage of days abstinent, in order to provide clinicians additional efficacy information. Study findings demonstrated a predicted therapeutic response to ondansetron, which increased the percentage of days abstinent relative to placebo for predetermined genotypes.

For men, who made up 73 percent of all subjects, high-risk drinking is defined as consuming five or more drinks per drinking day. This high risk has been associated with such severe health consequences as accidental injuries, deaths from external sources, aggression (both victim and perpetrator of), as well as numerous medical, legal and occupational problems.

The benefits of this type of personalized treatment approach are remarkably promising. Personalized medicine, or genome-based medicine, has the potential to give patient and their physicians the ability to make more informed treatment decisions.

"By being able to do genetic screening beforehand, clinicians can eliminate a great deal of the trial-and-error approach to prescribing medicine," Johnson said. "Personalized medicine allows them to better predict a successful treatment option, as well as reducing both premature medication changes and simultaneous multiple medication regimens."

Not all alcohol-dependent individuals are treated successfully with ondansetron.

"Although this treatment approach accounts for nearly one-third of patients with alcohol dependence, more research is needed to identify alcoholics with other genetic variations who will respond significantly to alternative medications," Johnson said. "Our findings, however, are a major step into the forefront of modern medicine."

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