Parkinson's drug linked to bizarre out-of-control urges
Mirapex and similar dopamine drugs seem to trigger potentially destructive side effects in some patientsJan 1, 2006 | Los Angeles Times
Faced with steady deterioration from Parkinson's disease, Jim Sweet leapt at the chance to try a new drug that promised to relieve the tremors brought on by the death of cells deep in his brain.
Like older Parkinson's medicines, Mirapex could bolster the fading supply of a critical brain chemical called dopamine. It was a blessing for Sweet until something unusual started happening.
First, he started buying things in eBay auctions a camera, a reclining leather chair, a big-screen TV, sunglasses, costume jewelry. He dived into online gambling, lottery tickets and penny stocks. Before long, he was disappearing for days to play slot machines near his home in Rancho Cucamonga, Calif.
He 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 recent University of Toronto study, as many as one 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 University of Southern California researchers.
People who claim 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.
Sweet 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 until one day nine years ago when his left arm froze 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 afflicts 500,000 to 1 million Americans, most of them elderly. Sweet was 38, 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 paralysis. There is no cure.
Sweet soon began taking the standard Parkinson's drug, levodopa, which is converted to dopamine in the brain.
The decades-old medicine carried some undesirable side effects, including involuntary tongue movements, grimacing and head bobbing. Sweet switched to Mirapex, marketed by German drug maker Boehringer Ingelheim.
The changes began in a matter of weeks, Sweet said.
His 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.
''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 slept with her wallet under her pillow and hid her jewelry. ''I couldn't trust him,'' she said. ``I had to protect the family.''
At the University of California, Los Angeles, Dr. Jeff Bronstein, a neurologist, tried to rein in Jim's gambling with counseling and drugs. There was no improvement. Bronstein finally turned his attention to Jim's Parkinson's medication.
Around the United States, other doctors started noticing odd behaviors in their patients.
An August 2003 report in the journal Neurology 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.
Soon, 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 mid-life preoccupations or irresponsible behavior appeared to be drug-induced personality shifts, Hui said. She had patients who had become obsessed with golf, sex, home decoration and gardening.
The root of the phenomena, scientists suspect, relates to 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, like 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 likely 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 past year, the companies have added information about compulsive reactions to their package inserts. Boehringer Ingelheim said it was working with Parkinson's experts to investigate reports of pathological reactions.
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.
Sweet, meanwhile, 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 recently settled a federal lawsuit against Boehringer Ingelheim and Pfizer Inc., which co-marketed Mirapex in the United States.