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Topiramate May Be Effective for Treating Patients With Alcohol Dependence
Topiramate appears to be safe and effective for curbing alcohol dependence, according to results reported in the October 10 issue of JAMA. Researchers found that topiramate was significantly superior to placebo in decreasing the percentage of heavy drinking days among alcohol-dependent individuals.
“Our finding in this study that topiramate is a safe and consistently efficacious medication for treating alcohol dependence is scientifically and clinically important,” stated Bankole A. Johnson, DSc, MD, PhD, Chairman and Alumni Professor in the Department of Psychiatry and Neurobehavioral Sciences, Professor of Medicine, and Professor of Neuroscience at the University of Virginia in Charlottesville, and colleagues. “Alcoholism ranks third and fifth on the US and global burdens of disease, respectively.”
A previous trial had shown that topiramate improved drinking outcomes in heavy drinkers, according to the investigators. However, the earlier trial was shorter, had a different study protocol, and was conducted at a single site.
Dr. Johnson and colleagues theorized that topiramate may decrease alcohol’s reinforcing effects “through facilitation of g-aminobutyric acid function and inhibition of glutaminergic pathways in the corticomesolimbic system.”
For the trial, conducted at 17 US sites, 371 heavy drinkers ages 18 to 65 were randomized to treatment with topiramate, up to 300 mg/day, or placebo and followed for 14 weeks. All participants received a brief, standardized, weekly psychosocial intervention emphasizing that medication adherence was necessary for changing their drinking behavior.
Men were considered to be heavy drinkers and eligible for enrollment if they had consumed 35 or more standard drinks per week during the 28-day period before their screening visit, while women were deemed eligible if they consumed 28 or more drinks per week. A standard drink referred to 0.5 oz of absolute alcohol, which was the equivalent of 10 oz of beer, 4 oz of wine, or 1 oz of 100-proof liquor. The two treatment groups were similar with respect to baseline demographic and psychopathologic characteristics.
Although the self-reported percentage of heavy drinking days was 81.9% for the entire study population prior to enrollment, that figure decreased to 43.8% in the topiramate cohort and 51.8% in the placebo cohort.
Topiramate also improved all other self-reported drinking outcomes and reduced plasma glutamate transpeptidase activity, the laboratory measure of alcohol consumption. In addition, the topiramate group achieved 28 or more days of continuous nonheavy drinking significantly faster than did the placebo group.
Adverse side effects that were more common in patients treated with the drug were paresthesia, taste perversion, anorexia, and difficulty with concentration. Overall, 18.6% of the topiramate group and 4.3% of the placebo group dropped out of the study because of side effects.
The investigators emphasized that the results confirm that alcohol-dependent individuals, while they are drinking heavily, can benefit from topiramate treatment—or that abstinence is not a precondition for using topiramate to treat alcohol dependence.
Dr. Johnson said in an interview that “all patients benefited” from topiramate treatment and that the findings are important because although other medications are available to treat alcoholism, “topiramate is an efficacious medicine, and unlike other medicines, it can be given at the point of maximum crisis—while the individual is still drinking heavily.”
He added that future studies will aim to identify possible genetic markers that may help determine “who will respond best to topiramate treatment before we offer it to patients.”
In an accompanying editorial, Mark L. Willenbring, MD, Director of Treatment and Recovery Research at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, commented that “topiramate produced significant and meaningful improvement in a wide variety of drinking outcomes.” Differences between the topiramate and placebo groups were still increasing at the end of the trial, thereby suggesting that longer treatment may yield additional improvement, he added.
—Jill Stein
Suggested Reading
Johnson BA, Rosenthal N, Capece JA, et al. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA. 2007;298(14):1641-1651.
Willenbring ML. Medications to treat alcohol dependence: adding to the continuum of care. JAMA. 2007;298(14):1691-1692.
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