Penn researchers study a drug that slows heavy drinking

Owen Mulhern, a retired financial planner, took topiramate to limit his drinking and found it successful. "I was no longer the craving fool. . . . I think of it as a miracle," he said.
Owen Mulhern, a retired financial planner, took topiramate to limit his drinking and found it successful. "I was no longer the craving fool. . . . I think of it as a miracle," he said. (MICHAEL S. WIRTZ / Staff Photographer)
Posted: February 28, 2014

Personalized medicine is all the rage in cancer treatment, as doctors increasingly tailor medicines to specific mutations in patients' tumors.

Now, the approach is making its way into addiction treatment.

A new study from the University of Pennsylvania found that heavy drinkers significantly reduced their drinking when they took the anticonvulsant drug topiramate - but only if they had a specific genetic profile.

Henry R. Kranzler, director of Penn's Center for Studies of Addiction and the study's lead author, said researchers also have found that genes affect response to two other drugs being tested in alcoholics: naltrexone and ondansetron, an antinausea drug.

Understanding the relationship between genetics and drug response, he said, could make clinical trials more efficient, because doctors could recruit only patients who are likely to be helped by a new treatment. It also could spare many patients the exposure to side effects from drugs that are unlikely to help them.

Currently, he said, "the pharmaceutical industry spends billions to develop drugs, and a lot of those are nothing more than shots in the dark, so there's an enormous amount of waste in that process."

While a drug like topiramate is not perfect for alcohol abuse because of its broader effects, studying why it works may help scientists develop treatments that home in on the brain's reaction to alcohol, Kranzler said.

In the meantime, he said, topiramate is "by far the most dependable drug for heavy drinking or alcohol dependence."

His study, which was started at the University of Connecticut Health Center and finished at Penn, aimed to reduce drinking, not stop it. That, he said, remains a controversial goal with groups like Alcoholics Anonymous that seek abstinence.

Heavy drinkers who can cut back are likely to reap health rewards, he said. Heavy drinking can lead to high blood pressure, stomach problems, weight gain, cognitive impairment, accidents, and family dysfunction.

In any given year, Kranzler said, 8.5 percent of Americans have an alcohol-use disorder.

The study enrolled 138 adults who drank heavily: at least 24 drinks a week for men and 18 for women. They had to drink heavily on at least two days of the week. That was five or more drinks for men and four or more for women. On average, they drank heavily five days a week.

Kranzler said that 90 percent of them qualified for alcohol-use disorder, the term psychiatrists now use for alcoholism.

Half received 12 weeks of treatment with topiramate and half received a placebo. Overall, the number of heavy drinking days per week fell from five to 2.35 in the placebo group and 1.12 in the topiramate group. However, it was a group with a particular genetic variant who were responsible for the difference. Their heavy drinking days fell to 0.75.

About 40 percent of European Americans have this genotype. Only about 4 percent of African Americans have it. Kranzler said Asians are in between.

The genes are believed to affect the function of the Kainate receptor. Topiramate blocks messages to that receptor, Kranzler said. Scientists don't know why that affects drinking. Kranzler said the receptor is involved in learning and memory. He suspects that it affects the "salience" of alcohol for drinkers. He said he, for instance, loves a good glass of wine, and says it is very salient for him: "I think about the taste of a wine I've really liked, and I relish it."

Drinkers who've taken topiramate said they "just stopped thinking about drinking," he said.

Long-term use of topiramate can cause glaucoma and kidney stones, Kranzler said. It also can cause cognitive problems, but a previous study found that patients had been drinking so much that their thinking improved on the drug.

Owen Mulhern, a retired financial planner who lives in Newtown Square, tried outpatient treatment, Alcoholics Anonymous, and naltrexone before starting topiramate a few months ago. He was not in Kranzler's study, but received treatment at Penn's Charles O'Brien Center for Addiction Treatment.

Mulhern, 67, said he had been drinking all of his life, but was a successful employee and business owner who restricted his drinking to evenings. "Work was always very important to me," he said. The amount he drank crept up over the years, though, and his family intervened about six years ago. At his peak, he was drinking 56 or 57 drinks a week: wine, beer and martinis. After taking naltrexone, he got it down to 22 to 30 drinks a week, but still wasn't satisfied.

He went to Penn five months ago and a doctor there added topiramate. He's now averaging seven drinks a week and has been as low as three. "Abstinence is beginning to look pretty good to me," he said.

His health never suffered from the drinking, but his relationships did. They're better and he has more energy and focus. He said he is now as happy with a "gigantic diet decaf iced tea" as with wine.

He said he felt big changes within a month of starting topiramate. "I was no longer the craving fool. Self-control was out the window. I no longer needed self-control," he said. "I think of it as a miracle."



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