Oct. 4, 2007 -- Researchers at the University of Virginia have led a multisite clinical trial showing that the drug topiramate is significantly more efficacious than placebo at curbing alcohol dependence. Subjects had to be drinking heavily and were not abstinent when they started the trial.
"Topiramate has emerged as a promising treatment for people with alcohol dependence,” says the lead author, Professor Bankole Johnson, D.Sc., M.D., Ph.D., M.Phil., FRCPsych., who is chairman of the U.Va. Department of Psychiatry and Neurobehavioral Sciences. “Our finding in this national study was that topiramate is a safe and highly efficacious medicine that can be paired with a 15-minute brief intervention by health practitioners who are not addiction specialists. Community practice settings in the United States and in many parts of the world, therefore, have the potential to use this combination treatment.”
Greater access to treatment with an effective medicine that can be delivered with a brief intervention by non-specialists should lead to success for many people battling the alcoholism disease, Prof. Johnson noted. “One of our next steps is to directly study topiramate’s efficacy in treating alcoholics within community practice settings.”
During the 14-week study published in the Oct. 10 issue of the Journal of the American Medical Association, 371 male and female alcoholics, all of whom were drinking heavily at the time of entering the trial, were randomly selected to take topiramate (up to 300 mg/day) or placebo. All of them had a weekly 15-minute intervention with a trained nurse to enhance adherence to the medication and treatment regimen. opiramate was previously approved by the Food and Drug Administration for seizures and migraine headaches and is manufactured by Ortho-McNeil Neurologics, Inc. Topiramate is not currently approved for the treatment of alcohol dependence.
Researchers approached the results as conservatively as possible, counting all dropouts or people who missed appointments as subjects who relapsed to their baseline drinking level. Even so, topiramate lowered the percentage of heavy drinking days (the number of days in which men and women consumed ≥5 drinks/day and ≥4 drinks/day, respectively, divided by the number of study days) by a mean of 8.44% more than placebo. The topiramate group had a reduction from 82% to a mean of 44% heavy drinking days during the 14 weeks, while the placebo group had a reduction from 82% to a mean of 52% heavy drinking days.
In a second analysis that tested the study hypothesis for all randomized participants who took at least one study medication dose and had at least one double-blind site visit, topiramate was much more efficacious than placebo, lowering the percentage of heavy drinking days by a mean of 16.19% more than placebo.
Additionally, for all secondary measures of self-reported drinking and the laboratory marker for drinking, gamma-glutamyltransferase in plasma, topiramate was more efficacious than placebo, according to both sets of analysis.
Importantly, both of these sets of analysis demonstrate the consistency and robustness of topiramate’s efficacy over placebo in treating alcohol dependence. Furthermore, this trial demonstrates that alcoholics who are drinking severely can begin to receive a safe and efficacious medicine immediately without having to undergo detoxification or stop drinking first — an important paradigm shift.
Ortho-McNeil Janssen Scientific Affairs provided the study medication, topiramate, and funding for this study.
Prof. Johnson’s previous work with topiramate was featured this year in the HBO documentary, Addiction, which in September won the prestigious Governor’s Award, a Special Emmy Award, from the Academy of Television Arts & Sciences. To view the portion of that documentary that features patients taking topiramate for alcohol dependence, go to:
For more information about topiramate, please visit www.uvaaddictiontrials.com.