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For the first time in alcohol addiction research, UVA 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," says Bankole Johnson, MD, PhD, study leader and professor and chair of the UVA

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 UVA scientists has found that specified variations in the serotonin transporter gene, SLC6A4, play a

significant role in influencing drinking intensity. Furthermore, past UVA 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, UVA researchers randomized alcoholics by genotype (LL vs. Sx and TT vs. Gx) 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 (NIAAA) of the National Institutes

of Health (NIH).
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 explains.
"The treatment response among those who received ondansetron was remarkable," says Johnson. "What this tells us is that we

have measurable evidence that personalized medicine is indeed a viable treatment for alcohol dependence.
An animation of how the medication works
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 comprised 73 percent of all subjects, high-risk drinking of alcohol 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.
For subjects with the LL/TT genotype, those treated with ondansetron, on average, fell below the high-risk drinking category,

while those who received placebo remained in the high-risk category. In addition, these same genotype categories responded

more positively to ondansetron, versus placebo, in increasing the days of abstinence.
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 says. "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," says

Johnson. "Our findings, however, are a major step into the forefront of modern medicine."
Source: UVA