Health

Parkinson's Drug May Trigger Compulsions

By SCOTT HENSLEY
Staff Reporter of THE WALL STREET JOURNAL

In a rare but troubling pattern, Parkinson's disease patients treated with drugs to calm their tremors sometimes become compulsive gamblers, doctors at the Mayo Clinic say.

In a paper encompassing hundreds of Parkinson's patients treated from 2002 to 2004, Mayo Clinic physicians outline 11 cases -- of nine men and two women -- who became compulsive gamblers after they were treated with commonly prescribed drugs that mimic the brain chemical dopamine.

After only occasionally gambling during his lifetime, one clinic patient, a 52-year-old man taking Mirapex, a Parkinson's drug from Boehringer Ingelheim GmbH, began to wager compulsively and lost $100,000 in casinos. He also became obsessed with sex, carrying on extramarital affairs and becoming fixated on pornography. One month after stopping the medicine, his wife said his problems were gone. "I have my old husband back," she told his physicians.

Other scientific reports have pointed to isolated gambling problems with some Parkinson's drugs. A previous report cited by the Mayo researchers, for instance, found such problems among 1.5% of 529 patients treated with Mirapex.

The current Mayo Clinic study, though, documents how specific drugs -- including Mirapex and GlaxoSmithKline PLC's Requip -- may be linked to the ill effects. It also cites how patients reverted to normal behavior after those medicines were halted. The study will be published in the September issue of the Archives of Neurology and was posted online yesterday afternoon.

Despite their findings, the Mayo Clinic researchers caution that physicians and patients shouldn't automatically forsake Parkinson's drugs, which they say are effective and safe most of the time.

Mark Vincent, a spokesman for Boehringer Ingelheim in the U.S., said the Ingelheim, Germany, company had received "rare reports of such behavior in individuals." The company added information about compulsive behaviors in the prescribing instructions for health-care providers late last year. The instructions for Mirapex now note some reports of "compulsive behaviors (including sexual and pathological gambling)."

At first, the Mayo Clinic patients were a source of curiosity for their doctors, who didn't see an immediate connection to the Parkinson's drugs."The patient might have sheepishly admitted they were gambling a lot or a family member might have told on them," says Leann Dodd, lead author of the clinic's paper.

The Mayo Clinic doctors tested their own suspicions by tapering the patients off the medicines. "The results were striking," Dr. Dodd said. The gambling and other compulsive behavior, such as excessive eating and sexual fixations, stopped in eight patients when the medication was withdrawn. The outcome for the other three was unknown because they weren't available for follow-up examinations.

Parkinson's disease, a degenerative disorder marked by the loss of neurons in a region of the brain called the substantia nigra, affects men and women equally. The condition, diagnosed in 60,000 Americans each year, is treated with drugs that restore dopamine or act to replace its effects. Dopamine helps regulate movement, but it also is a key player in the brain's pleasure center and thus can reinforce many behaviors.

Mirapex, more than the other Parkinson's drugs, exerts a particularly powerful grip on what are called D3 receptors for dopamine, according to the Mayo researchers. The Mayo Clinic doctors think Mirapex, known generically as pramipexole, may be hyperstimulating for some people and send their search for pleasure into overdrive.

Some patients say problems with Mirapex should have been made known much earlier -- prior to the Mirapex labeling change.

In May, a lawsuit seeking class-action status was filed in Superior Court of Justice in Toronto against Boerhinger-Ingelheim and Pfizer Inc. of New York, which co-marketed the drug until early this year. The lead plaintiff, a 56-year-old from Ontario, lost his house and life's savings after gambling away more than 100,000 Canadian dollars, or about $82,000. He claims the companies didn't adequately warn patients and doctors about the potential for problems. A separate lawsuit seeking class-action status in the U.S. was filed late last month in federal district court in Riverside, Calif.

Boehringer Ingelheim's Mr. Vincent declined to comment on the continuing litigation.

GlaxoSmithKline says it has reviewed clinical-study databases, reports from doctors and publicly available data sources concerning its Requip, known generically as ropinirole, without seeing signs of a link to compulsive behaviors. The drug's label doesn't mention any such problems.

Physicians, meanwhile, are grappling with how to address an issue that is far from black and white. "We're familiar with this problem, but I don't know that we have a clear idea" about how frequently it occurs, says Carlos Singer, director of the movement disorders division at the University of Miami School of Medicine.

Dr. Singer says educating patients about the risk is the first line of defense. Patients aware of behavioral changes may be able to avoid trouble. Other drugs, such as amantadine or levadopa, can be tried, too. They have their own side effects, however, he said.

Not all patients, even those who suffer ill effects, immediately opt to cease taking the Parkinson's drugs. One man who has joined the Canadian suit is John Murray, a retired financial planner in Ontario. After taking Mirapex at high doses in 2003, he started gambling online, losing nearly C$50,000.

He still is taking Mirapex, which has relieved his Parkinson's symptoms to the extent that he now can golf. He has turned over control of the family finances to his wife, and is now a member of Gamblers Anonymous. He says he plans to talk to his neurologist soon about alternative medicines.

Write to Scott Hensley at scott.hensley@wsj.com