An epilepsy drug may help alcoholics stop drinking.
By Temma Ehrenfeld
Donald Elbel remembers sneaking into the garage as a 10-year-old to steal beers from his dad's cooler. By the time he was 40 and working as a mechanic in Kendalia, Texas, Elbel was chugging 35 Lone Stars a day. He knew his life was in danger--he once slammed his car into a telephone pole at 80 miles an hour and, after a short detour to the hospital, ended up in jail. He tried everything from Alcoholics Anonymous to hospital detox, but he couldn't give up the brew. Then, in 1998, Elbel volunteered for a clinical trial of a drug called topiramate, a well-known seizure medication. He wasn't required to stay sober, but after a few days of oral medication, he lost interest in drinking. "I went around at first saying 'Something's missing,' but I didn't know what," says Elbel. "The doctors had to tell me I was missing the craving." Though he took the drug for only three months, Elbel hasn't touched a beer in seven years.
It sounds like magic, but over the past decade scientists have come to better understand how the addicted brain works. And they are using that knowledge to study several existing drugs as potential treatments for the millions enslaved by their cravings. The leading candidate may be topiramate, known commercially as Topamax. For years, epileptic patients reported that it helped them fight food cravings and lose weight. Now, in addition to helping alcoholics, the drug shows promise in early studies with binge eaters, smokers and even gamblers. Because these drugs have a record of safety, doctors may legally use them to treat addiction long before they are officially approved for that purpose, a practice known as off-label prescribing.
Addiction is a kind of brain damage. In a normal brain, a neurotransmitter called glutamate is released when a person experiences desire. It's essentially a "go" signal. Counteracting glutamate is a neurotransmitter called GABA (gamma-aminobutyric acid), an inhibitor that keeps glutamate and other go signals from overwhelming us. The strength of a craving depends on the balance of glutamate and GABA in the brain. When an addict confronts a martini or cigarette, theory has it, GABA is overwhelmed by glutamate--desire trumps inhibition. The brain then becomes flooded with dopamine, our master pleasure chemical, reinforcing the original desire.
Topiramate works on both ends of the GABA-glutamate seesaw: it reduces the release of glutamate and enhances the release of GABA. In the Texas study Elbel took part in, 17 percent of hard-core drinkers stayed dry for at least a month while taking the drug. An additional 20 percent cut back from heavy consumption to more normal levels. The drug does have side effects, most commonly mental fuzziness, but patients tend to stick with it, says study author Bankole Johnson of the University of Virginia. A multisite study to confirm his findings is underway.
None of the currently approved treatments for alcoholism acts on the mechanism of addiction as directly as scientists would like, and none has achieved wide-spread acceptance or success. The oldest and best-known is disulfiram, or Antabuse, which makes people vomit as soon as they drink but doesn't reduce cravings. Two other drugs, acamprosate and naltrexone, seem to cut cravings, but each has disadvantages. Acamprosate works well only if patients stop drinking before treatment. If they relapse, acamprosate keeps them from bingeing as badly. Naltrexone also moderates binges and can be taken while the patient continues to drink, but may be most effective only for people with a specific genetic vulnerability.
Meanwhile, up north in Fairbanks, Alaska, internist Linda Garcia has already treated two dozen alcoholics with topiramate, along with hypnosis and nutritional supplements. "My patients tell me that they no longer have the fear that comes with craving," says Garcia, who is especially happy that she's beginning to attract patients from the hard-hit Alaska Native population.
In addition to topiramate, other established drugs are being studied as potential treatments for addiction. Among them are baclofen, a common muscle relaxant that enhances GABA, and N-acetylcysteine, used to treat Tylenol overdoses, which inhibits glutamate. Scientists don't yet know which of these, if any, will emerge as effective and reliable treatments for addiction. But there's hope, and for people like Donald Elbel, that's something to live for.