A New Treatment for Alcohol Dependence?

Several news outlets have today picked up on an apparently odd report: topiramate, a medicine used for migraine and seizures, may also help some people who are alcohol dependent.

A 14-week multicenter clinical trial was orchestrated by researchers at the University of Virginia, and published today in 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.

Trials of people with substance abuse are always complicated by high non-compliance rates. Some studies skew their results by making the questionable assumption that if someone doesn’t show up, then they must be cured! This study was structured more realistically: dropouts were assumed to have relapsed to their baseline drinking level.

Even when the dropouts were included, topiramate lowered the percentage of heavy drinking days (the number of days in which men consumed ≥5 drinks/day and women drank ≥4 drinks/day, divided by the number of study days) by a mean of 8.44% more than placebo. The topiramate group showed 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.

Topiramate was more efficacious than placebo, on measures of self-reported drinking and the liver enzyme gamma-glutamyltransferase, which is a sensitive marker of alcohol consumption.

There are some good reasons why topiramate may be helpful: it acts on gamma-aminobutyric acid receptors in the brain, which have been implicated in some addictive behaviors, including over-eating.

A few years ago topiramate was being examined as a possible weight loss agent, since it has effects on feeding and on metabolism.

The trials have been suspended in North America, primarily because of one of the main side effects of topiramate: it may cause cognitive dulling and word finding difficulties in some people. Those side effects sometimes take a few weeks to develop.

A second point is that when it is used for weight management, some people quickly develop tolerance to its effects.

This new study is interesting and may turn out to be very important. We shall have to see whether the effect on alcoholics is robust and sustained over time.

“All excess is ill, but drunkenness is of the worst sort. It spoils health, dismounts the mind, and unmans men. It reveals secrets, is quarrelsome, lascivious, impudent, dangerous and bad.”
–William Penn (English Quaker, Colonizer in America and Founder of Pennsylvania, 1644-1718)

“One reason I don’t drink is that I want to know when I am having a good time.”
–Nancy Lady Astor (American-born British Politician, 1879-1964)

“Hide our ignorance as we will, an evening of wine soon reveals it.”
–Heraclitus (Greek Philosopher, c.540-480 B.C.E.)

“Where the drink goes in, there the wit goes out.”
–George Herbert (English Religious Poet, 1593-1633)