Source: Washington Post
Date: 19 March 2006

Prescription For an Obsession? Gambling, Sex Manias
Called Surprise Risks Of Parkinson's Drugs

By Shankar Vedantam
Washington Post Staff Writer

When Wayne Kanuch received a diagnosis of Parkinson's disease in 1993, the last thing he imagined was that the drug prescribed to treat his illness would turn him into a compulsive gambler and put his libido into overdrive.

Kanuch's marriage ended in divorce, partly as a result of the sexual pressures he placed on his wife, and he began losing fortunes at the racetrack. He was fired from his job at Chevron for trolling for dates on the Internet while at work, and he quickly went bankrupt.

"I contemplated suicide a couple of times," he said in an interview last week. "Everyone was blaming me, and I was looking at the mirror and blaming myself and asking why I could not stop."

New evidence unearthed by scientists at the Food and Drug Administration, Duke University and other centers suggest the reason Kanuch could not stop is that the drug being used to treat Parkinson's boosted the level of dopamine in his brain. Researchers are looking into the possibility that dopamine, which is associated with a host of addictive behaviors, may turn some Parkinson's patients into obsessive pleasure seekers.

Now, some patients are suing the manufacturers of these drugs to recover the money they lost gambling, on the grounds that the companies did not do enough to warn about these risks. Kanuch has not yet sued but plans to do so.

So far, there is no definitive evidence on the connection between dopamine enhancers, known as agonists, and compulsive gambling. The behavioral anomalies, though dramatic, are probably rare among the thousands of Parkinson's sufferers who take the drugs. There have been no controlled studies looking into the possible link.

Drug manufacturers say anecdotal reports from patients such as Kanuch do not constitute scientific evidence, but they say they have updated warning labels anyway. Valeant Pharmaceuticals, which sells Permax, a dopamine agonist, said the matter is under litigation but it has told physicians: "As with other dopamine agonists, compulsive self-rewarding behavior (e.g., pathologic gambling) and libido increase have been reported in patients."

Boehringer Ingelheim, which makes Mirapex, another dopamine agonist, said it has toughened its warning label but said that company officials are still exploring the connection. Eli Lilly & Co, which used to sell Permax, said there is no scientific consensus on the issue and suggested that gambling problems may be linked to the increased accessibility of legalized gambling.

Still, a recent analysis headed by FDA scientist Ana Szarfman found a strong association between pathological gambling and dopamine agonists. The statistics from a federal adverse-events database are not conclusive, but FDA officials regularly mine the data to spot red flags.

"There is decent biochemical plausibility that chemical changes can lead to impulsivity and acts like pathologic gambling," said Duke University psychiatrist P. Murali Doraiswamy, co-author of the analysis, published in Archives of Neurology.

"It is certainly plausible that gambling can be a side effect of a drug that excessively stimulates limbic-system dopamine," Doraiswamy said.

The notion that brain chemicals play a powerful -- but hidden -- role in human behavior is at odds with American convictions about free will and choice. Kanuch and other patients said they spent years believing they were responsible for their actions, only to find that the impulse for self-destructive behaviors vanished once they stopped taking a drug.

"I broke down in tears and cried my heart out," Kanuch said. "I could not believe a drug could cause that kind of problem. The more I read, I grew convinced and grew angrier."

Several patients said the behaviors proved so destructive that they preferred the diseases that the medications were trying to treat.

Kanuch, 52, who shuttles between living arrangements in the Texas towns of Missouri City and Katy after bankruptcy and several evictions and run-ins with the law, said he is planning to file suit against the maker of Mirapex. The man who had a 21-year career with Chevron said he lost $350,000, his marriage and numerous friends from whom he borrowed money for gambling.

"I was misled by doctors," he said. "They may not know all the side effects, but as early as 1993 there was case history building. My doctor was not aware of this. When I told him there was an issue, he denied there was a problem."

Several other patients report similar obsessions. Cindy Still of Roseburg, Ore., said that after 29 years of faithful marriage, another dopamine agonist -- a physician thought the drug might help ease her chronic depression -- caused her to start an affair, quit her religion and become a compulsive gambler.

Peggy Andresen, 51, of Redmond, Wash., developed obsessions with gambling -- and painting tables and counters to look like marble. Mirapex is a great drug, she said, but "the top of every bottle needs to have a big red sticker that says 'May Cause Gambling.' "

Barbara Hermansen, 52, of Winnetka, Ill., said she was prescribed Permax in 1996 for restless-leg syndrome, in which patients feel electrical impulses crawling under their skin when they lie down to sleep -- and causing debilitating bouts of insomnia.

The drug worked like a charm, and her physician steadily increased the dose, which tends to be necessary -- by 2001, she was on 40 times her original dose. On a weekend visit to Las Vegas with her sister, Hermansen dropped $300, which surprised the Sunday-school teacher because before that she had been in a casino twice before and could not wait to get out.

On returning home, the financially conservative lawyer began gambling over the Internet. She maxed out her credit cards, emptied her retirement accounts and sold jewelry to fuel the gambling. When she confessed to her husband after losing about $15,000, she said he was incredulous because she had been so staid when it came to finances.

Hermansen promised she would never do it again, and she put a filter on her computer to block the gambling Web sites. She soon found herself driving to casinos. After confessing again, she got herself voluntarily banned from Illinois casinos. Then she started driving to casinos in Indiana.

"I won huge amounts of money," she said. "I stood in front of a machine and won $62,000 and $28,000 in single spins."

But, as is true for many people with gambling problems, the money proved to be almost beside the point. With one exception, she never walked out of a casino with money: "You never walk away, you always put it back in, because no amount of money is enough," she said.

When a grocer gave her a bottle of champagne for being such a good customer for scratch-off lottery tickets, Hermansen said she was so humiliated and disgusted at herself that she wished "the earth would open and swallow me."

By 2004, believing she could never stop, she resolved to drown herself by taking a sleeping pill and swimming out into Lake Michigan. But as she sat in her car with her bathing suit beside her and a sleeping pill in her pocket, she realized she could not bear to leave her husband and children.

When Hermansen asked her neurologist if the drug might be the problem, he said he did not know of a connection. At a Gamblers Anonymous meeting, the theory was booed down and she was told she needed to take responsibility for her actions. A therapist suggested she was testing her husband's love because she felt she didn't deserve to be happy; a psychiatrist told her to make a list of all the reasons she was trying to sabotage her life.

When an expert in pathological gambling finally took her off the drug, the urge to gamble vanished. The restless-leg syndrome came back with a vengeance, but Hermansen swears that she would rather "suffer from insomnia for the rest of my life rather than go through that gambling hell."

Hermansen sued Eli Lilly to recover hundreds of thousands of dollars she lost gambling, and because she says the company was unresponsive to her plea for warnings.

A move to turn the lawsuits into a class action was denied late last year, because of the diversity of the cases, and now individual lawsuits are accumulating around the country, said Daniel Kodam, a lawyer with Soheila Azizi and Associates in Rancho Cucamonga, Calif. Kodam is representing Joe Neglia of Millersville, Md., a former Defense Department intelligence analyst who turned to compulsive gambling after taking Mirapex for Parkinson's disease.

Kodam dismissed the existing warnings as too little too late: "The warning label is a joke," he said. "To bury five to six words on Page 17 when the effects are so catastrophic is ridiculous. You need a clear descriptive warning label and notification to doctors to ask patients about this potential effect."

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Entacapone (Comtan)
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The dopamine transporter
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Parkinson's disease: resources
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Hedonistic homeostatic dysregulation
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