Compulsive Behavior Triggered by Mirapex

First, he started buying things in EBay auctions — a camera, a leather reclining chair, a big-screen TV, sunglasses, costume jewelry and dozens of other items. He dived into online gambling, lottery tickets and penny stocks. Before long, he was disappearing for days to play slot machines at Indian casinos near his home in Rancho Cucamonga.

He ran through his savings and pawned his CD collection, his children's video game player and his wedding ring.

Gambling "was something I could not turn off," said Sweet, a 45-year-old former middle school teacher.

Although Mirapex and similar dopamine drugs have helped thousands of Parkinson's patients, researchers are beginning to detect a small group for which the medicine seems to act like a jolt of electricity, triggering bizarre, out-of-control urges.

According to a University of Toronto study presented last month, as many as 1 in 15 patients taking the drugs — potentially thousands of people — may have compulsive reactions.

An elderly California widower started wearing dresses, heels and lipstick; one man became obsessed with fast driving and abandoned his job to ride a jet ski up the California coast, according to a study by USC researchers.

Drug makers say they are monitoring reports but so far the rate of compulsions does not exceed that of the general population. One company chalked up complaints to coincidence.

"If someone takes an aspirin and they gamble, does that mean the aspirin did it?" asked Dr. David Hosford, a scientist at GlaxoSmithKline, maker of the dopamine drug Requip.

People who say their lives were shattered by their strange urges have filed lawsuits against drug makers. Although their compulsions disappeared after they stopped taking the drugs, some patients say they are still haunted by their experiences.

After spending $20,000 on prostitutes, phone sex and pornographic films, a married churchgoer in his 50s said he was troubled by the sexual desires seemingly uncorked by the drug.

"Was that the monster in the closet?" asked the man, a participant in a USC study who did not want his name published out of embarrassment. "Is that who I am really and the drug just opened the door?"

Sweet, a compact man who once studied for the ministry, can only guess where his compulsion came from.

He had barely been inside a casino before, although he remembered he and his wife once won $800 in Las Vegas. Thrilled, they bought an entertainment center for the family.

His life was happy and predictable — until one day nine years ago when his left arm froze against his side during a church league basketball game. Weeks later, his arm shook as he grasped the hand of a teammate to form a prayer circle.

They were the first signs of Parkinson's disease, which affects 500,000 to 1 million Americans, most of them elderly. Sweet was 36, the father of two young children.

Parkinson's is caused by the death of cells that produce dopamine, a neurotransmitter that carries messages along the brain's pathways. A shortage of the chemical causes poor coordination, shaking and bad balance. With time, symptoms include incontinence, difficulty talking and sudden paralysis. There is no cure.

Sweet soon began taking the standard Parkinson's drug, levodopa, which is converted to dopamine in the brain.

Although his tremors disappeared, Sweet knew the decades-old medicine carried some undesirable side effects, including involuntary tongue movements, grimacing and head bobbing. So he switched to Mirapex, marketed by German drug maker Boehringer Ingelheim. The drug, which did not carry those side effects, had been approved a year earlier for patients in the early stages of Parkinson's.

Half of the Parkinson's patients in the U.S. take Mirapex or similar drugs, which are also used to treat people with restless legs syndrome and those with depression that doesn't respond to other medicines.

The changes began in a matter of weeks, Sweet said.

Sweet's wife, Kris, said she noticed him spending all his free time at the computer. For the first seven years of marriage, the couple never had a credit card balance. Now their debt was mounting from stock and online gambling losses.

Kris removed the computer from their house. Jim continued his online gambling on computers at the local Kinko's copy center. During breaks, he would bolt from school and return with fistfuls of lottery tickets.

Trips to nearby casinos soon drove him into bankruptcy with a $120,000 debt on 16 credit cards.

Jim knew he had spun out of control. He didn't enjoy gambling, yet he couldn't control his urge for more than a few hours.

"It was like being outside yourself, watching as you do these horrible things," he said. "I was still Jim. I still cared. I was trapped inside my mind."

Kris filed for divorce three times, but each time withdrew the court documents because she had a suspicion his disease was to blame. Still, she slept with her wallet under her pillow and hid her jewelry.

"I couldn't trust him," she said. "I had to protect the family."

Desperate to figure out what was happening to him, Jim eventually ended up at UCLA.

Dr. Jeff Bronstein, a neurologist, tried to rein in Jim's gambling with counseling and drugs. There was no improvement.

One thing was left. Bronstein finally turned his attention to Jim's Parkinson's medication.

Around the country, other doctors started noticing odd behaviors in their patients, and case reports began appearing in medical journals.

Among the first was an August 2003 report in the journal Neurology that linked the drugs to gambling in eight Arizona patients. Although the rate was the same as in the general population, the drug appeared to act as a trigger in patients, who stopped gambling when the medicine was discontinued. Dr. Mark Stacy said he conducted the study after the wives of two patients told him their husbands had become gamblers.

With each subsequent report, a fuller picture emerged. At a meeting of the Movement Disorders Society in 2004, Dr. Jennifer Hui, a neurologist, and her colleagues at USC said patients' odd behaviors weren't limited to gambling.

What friends and families dismissed as quirky midlife preoccupations or irresponsible behavior appeared to be drug-induced personality shifts making patients enamored of things they often had little interest in before, Hui said. She had patients who had become obsessed with golf, sex, home decoration and gardening.

Reactions have included anything patients found rewarding.

Gary Boyd of Houston had started a Hot Wheels toy collection with his son, but it became an obsession after he started taking Mirapex five years ago.

At one point, the 50-year-old traded his wife's old Toyota for 25 cases of the toy vehicles. Boyd said his marriage ended in divorce in part because his wife was infuriated by the Hot Wheels stuffed into every closet.

"It will be years before I can drive past a Wal-Mart and not stop and go into the toy department," said Boyd, who still takes Mirapex for his Parkinson's but has gradually learned to control his collecting.

Not all the compulsions are destructive.

After starting on Requip and levodopa, Mary Moody, 62, launched into a binge of composing religious hymns.

A former classroom aide in Augusta, Ga., she used to grab paper from the trash so she could scribble down lyrics when the urge hit. At home, bits of paper with phrases inspired by the psalms littered her house. Although she can't read music, Moody plucked out melodies on an old family piano.

"I'd rather do this than anything else in the world," she said.

The root of the phenomenon, scientists suspect, lies in the complex role of dopamine in the brain.

Not only does the chemical carry messages that convert thought to movement, but it also stimulates a part of the brain, the limbic region, that controls feelings of reward and well-being. Gambling, sex, addictive drugs and some habits, such as playing video games, are known to stimulate the release of dopamine in the limbic region.

"Without dopamine we would never be addicted to cocaine, cigarettes, heroin or anything," said Northwestern University scientist D. James Surmeier.

Writing in Neurology last September, a team from the Mayo Clinic in Rochester, Minn., found that the dopamine drugs had a strong attraction to nerve cells found in large numbers in the limbic region and probably overstimulated the area.

Surmeier, a dopamine expert, called the link to cells in the limbic region "a smoking gun."

In February, a Food and Drug Administration study published in Neurology found a strong association between the drugs and pathological gambling, although the total number of complaints received by the agency was small.

Within the last year, drug companies have added information to their package inserts about compulsive reactions. Boehringer Ingelheim said it was working with Parkinson's experts to investigate reports of pathological reactions.

Valeant Pharmaceuticals, which sells Permax, sent a letter to doctors in February saying that compulsive behaviors had been reported in less than 1 in 10,000 patients taking Permax. Still, the Costa Mesa company wrote that it could not rule out a drug link.

The fact is no one knows how many patients develop compulsions. Coming up with a figure is difficult because behaviors vary and no large clinical trial has studied the phenomenon. Doctors say the drugs are valuable and most patients take them without undergoing personality shifts.

Why compulsive reactions seem to grip only a minority of patients is a mystery. Some researchers speculate that genetic differences among individuals in the number and variation of dopamine receptors are to blame.

For patients who need the drugs to manage the inexorable progression of Parkinson's, options are limited. Lowering drug doses seems to eliminate compulsions in some patients, doctors say. Other patients have channeled their obsessions into more productive behaviors.

After losing $100,000, retired businessman James Newton, 60, went from gambler to golfer.

Newton spends five hours each day on the course near his home in Myrtle Beach, S.C., leaving him too exhausted to buy lottery tickets or gamble online. Nonetheless, as an added safeguard, he tore up his credit cards and handed his wife total control over their finances. Before he heads to the links, his wife gives him a few dollars for tips.

Newton said he was grateful for Mirapex and couldn't function without it, which he takes with levodopa. But, he said, "the urge to gamble does not go away."

Sweet still can't completely forget the three years when gambling overwhelmed his life.

After doctors at UCLA took him off Mirapex, "it was like a weight being lifted from my head," said Sweet, who this month settled a federal lawsuit against Boehringer Ingelheim and Pfizer Inc., which co-marketed Mirapex in the U.S.

His lost savings and poor credit weigh on his mind. A creaky step reminds his wife of how he would sneak out to a casino.

Even now, four years since he stopped gambling, his 12-year-old daughter still runs after him when he leaves to make sure he is coming back.

"For three years, they couldn't trust me at all," Sweet said. "It is going to take time to build up that trust again."