Overstimulated

"I fretted and kind of rocked back and forth on the observation," says Stacy, director of the Movement Disorders Clinic at Duke University. "I didn't want to create a false uproar."

Prompted by colleagues, Stacy eventually published his findings in the journal Neurology in August 2003.

The study led to an outpouring of media attention. Stacy received thank-you letters and testimonials from Parkinson's patients from across the country and around the world whose lives were upended after taking the dopamine agonists. Relationships were destroyed, families ripped apart by financial ruin, infidelity and divorce.

In July psychologist M. Leann Dodd of the Minnesota-based Mayo Clinic published a report in the Archives of Neurology that took the Stacy study a step further. During a two-year span Dodd treated 11 Parkinson's patients who became pathological gamblers. In nine of those cases, the patients were prescribed the dopamine agonist Mirapex, or pramipexole dihydrochloride. Mirapex, in particular, Dodd found, had the greatest potential to wreak havoc on the brain's limbic system -- the area related to pleasure, mood and disinhibition.

The Dodd study could have dire consequences for the once-touted wonder drug. Mirapex, since receiving FDA approval in 1997, has fast become one of the top-selling Parkinson's drugs on the market, recording more than $200 million in U.S. sales alone for the last several years. It's also among the most heavily marketed Parkinson's drugs, according to neurologists who say they are deluged by free samples and brochures.

Unlike Stacy, Dodd included in her report the extent of personal damages suffered by these patients. They included a 52-year-old married man who gambled away $100,000, gained 50 pounds, became addicted to pornography and engaged in extramarital affairs; a 68-year-old married man who lost $200,000 at casinos in just six months and became hypersexual, "leaving town for days without anyone knowing his whereabouts"; and a 54-year-old married pastor who began to gamble daily and kept the addiction a secret from his wife.

"What actually triggers the patient to take that first walk into the casino or to have that first affair, I don't really know what is doing that," Dodd says. "But once the behavior stimulates this reward area, it becomes so important to get the reward over and over and over again.

"It's much like a drug addiction -- like people who take cocaine or meth and have to go back and get more and more and more."

The Stacy and Dodd studies triggered a pair of class-action lawsuits based in Canada and Southern California. These suits allege that pharmaceutical giants Boehringer Ingelheim Pharmaceuticals Inc., which manufactures Mirapex, and Pfizer Inc., which co-markets Mirapex, failed to warn doctors and patients that taking the drug could lead to pathological behavior.

Earlier this year, Boehringer Ingelheim added a new warning to the "Important Product Information" section on its Mirapex Web site, citing "compulsive behaviors (including sexual and pathological gambling)" as possible side effects. But critics say the seven-word phrase, buried on page 17 of a 21-page technical document, is insufficient warning.

"That's not a warning label -- it's a joke," says Daniel Kodam of Soheila Azizi & Associates, lead attorney in the California-based class-action suit. "This is something that should have been discovered in the clinical trials."

A Pfizer spokeswoman declined to comment on the suit; Boehringer Ingelheim didn't respond to several phone calls.

Kodam says he's been "bombarded" by testimonials from affected Mirapex patients since the Dodd report was released. The number of plaintiffs represented in the class-action suit has more than doubled and now comprises some 400 people from across the country, including two dozen Texans.

"We suspect the number of people affected is in the thousands," Kodam says.

Plaintiffs include Peggy Andressen, 51, from Seattle, Washington, who claims she opened accounts at more than 60 online casinos, losing some $1.2 million in four years; Alan Hahn, 56, a financials trader from Schaumburg, Illinois, who says he not only bankrupted himself but also gambled away more than $250,000 entrusted to him by clients; and David Neal, 58, from Palm Springs, California, who says he drove to casinos as many as 12 times a day, losing $250,000 in six weeks.

All of these patients say they had never suffered an addiction, gambling or otherwise, until they were prescribed Mirapex.

"I'd always been a disciplined, responsible person," Neal says, echoing the others. "My whole personality changed completely. I became a madman."

The Stacy and Dodd studies have received much publicity. But other, more obscure reports linking Parkinson's medications to bizarre, compulsive behaviors date back to the mid- to late '90s.

For instance, about a year before the Stacy study appeared, neurologists in Ecuador reported that four patients developed pathological gambling addictions, anxiety disorders and obsessive-compulsive disorders after taking levodopa for more than eight years. They included a 50-year-old man who began showering seven times a day and a 64-year-old woman who brushed her hair for hours every day because "she felt as if her hair was slithering on her head."

One 71-year-old man, the report stated, developed "an intense preoccupation with the presence of ants in his apartment. He spent several hours daily hunting them by spraying insecticides or placing poison on every corner; he said that if he did not kill them, they would swallow him up. It was not uncommon for him to wake up at midnight and go hunting ants or suddenly start doing so while he had visitors. If someone tried to stop him by reasoning with him about his absurd behavior…he scratched vigorously all over his body."