Topiramate may be a promising treatment for alcohol dependence, significantly decreasing heavy drinking days and increasing days of abstinence, compared with placebo, Dr. Bankole A. Johnson and his colleagues reported.
“This is a different paradigm, and it gives us another way to try and treat alcoholics,” said Dr. Johnson, chair of the department of psychiatry and neurobehavioral sciences at the University of Virginia, Charlottesville, when he initially unveiled the data at the annual meeting of the Research Society on Alcoholism in Washington.
“The way we had before was to detox them by some method and then see if they relapse. But they may not need to do that,” Dr. Johnson pointed out. “You can start them [on topiramate] while they're still drinking heavily.”
The 14-week, placebo-controlled trial randomized 371 patients with alcohol dependence (mean age 47 years) to either placebo or up to 300 mg topiramate (Topamax) daily. Most of the patients (72%) were men; about 85% were white (JAMA 2007;298:1641-51).
At baseline, all the men in the study were drinking at least 35 drinks per week; the women were drinking at least 28 per week. Patients recorded their baseline alcohol consumption for 1 week as part of the screening process. They also recorded their daily drinking throughout the study.
Topiramate was significantly more effective than placebo in reducing the percentage of heavy drinking days from baseline to week 14 (82% to 44% for topiramate and 82% to 52% for placebo).
Patients taking the drug had a mean of 7% more abstinent days than did those taking placebo, a significant difference. They also drank a mean of one fewer drink per drinking day than did those taking placebo.
Topiramate was associated with significantly lower levels of gamma-glutamyltransferase, an objective measure of recent alcohol consumption.
Patients taking topiramate were almost three times more likely than were placebo patients to achieve 28 or more continuous days of nonheavy drinking, and six times more likely to achieve 28 or more days of abstinence.
Adverse events that were more common in the topiramate group included paresthesia (51% vs. 11%), taste perversion (23% vs. 5%), anorexia (20% vs. 7%), and difficulty with concentration (15% vs. 3%). Attrition attributable to adverse events was 18% for topiramate and 4% for placebo.
The authors noted that their results might not be applicable to most people seeking treatment for alcohol dependence. “As with most clinical trials [in this field], enrolled patients have to meet criteria enabling the conduct of a safe study. Because this cohort is often relatively healthier and perhaps more homogenous than the general population of all those seeking treatment for alcohol dependence, our ability to generalize without restriction from this trial to clinical practice is limited.”
Nonetheless, wrote Dr. Mark L. Willenbring in the accompanying editorial, topiramate may represent a new and valuable tool for primary care physicians. Most have little formal training in treating alcohol use disorders and do not feel qualified to care for these patients, wrote Dr. Willenbring, of the National Institute on Alcohol Abuse and Alcoholism. The usual course is to refer to a specialist (JAMA 2007;298:1691-2).
“However, access to specialized treatment has become more difficult in the last decade, and although the prevalence of alcohol use disorders has not changed substantially, even fewer patients receive treatment than did 10 years ago.”
Dr. Johnson disclosed that he is a consultant for several pharmaceutical companies, including Ortho-McNeil Janssen Scientific Affairs LLC. (Ortho-McNeil Inc. is the maker of Topamax.) Dr. Willenbring reported no disclosures.
'This is a different paradigm. … You can start them [on topiramate] while they're still drinking heavily.' DR. JOHNSON