Tremor drug linked to odd compulsions
Parkinson's patients reported to begin gambling, buying spreesJun 4, 2006 | Baltimore Sun 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 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, Calif.
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, 45, a 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 trigger 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 - might have such 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.
The companies 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?" said Dr. David Hosford, a scientist at GlaxoSmithKline, maker of the dopamine drug Requip.
People who claim their lives were shattered by their strange urges have filed lawsuits against drugmakers. Although their compulsions disappeared after they stopped taking the drugs, some patients say they are still haunted by their experiences.
Sweet, who once studied for the ministry, said he 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 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 afflicts 500,000 to 1 million Americans, most of them elderly. Sweet was 38, with 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 Parkinson's patients in the U.S. now take Mirapex or similar drugs, which are also used to treat people with restless-leg 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.
"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 Sweet 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 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.
One thing was left. Bronstein finally turned his attention to Jim's Parkinson's medication.
Around the U.S., other doctors had started noticing odd behaviors in their patients, and 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.
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 mid-life quirks or irresponsible behavior appeared to be drug-induced personality shifts making patients enamored with things they often had little interest in before, Hui said. She had patients who had become obsessed with golf, sex, home decoration and gardening.
The root of the phenomena, scientists suspect, is 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 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.
The drug 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.
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.
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 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."