"This is a striking effect," says J. Eric Ahlskog, M.D., Ph.D., Mayo Clinic neurologist who treated most of the patients in the series. "Pathological gambling induced by a drug is really quite unusual."
The good news, according to Dr. Ahlskog and M. Leann Dodd, M.D., Mayo Clinic psychiatrist who spearheaded the analysis, is that excessive gambling behavior only occurs in a small number of patients given the drugs, and it can be stopped as suddenly as it came on. "It's a very rare side effect and reversible if you get off the drug, but you have to make the association," says Dr. Ahlskog.
The Mayo Clinic neurologists treating the Parkinson's patients reported in the case series analysis learned about the gambling issues of the 11 patients in the series during routine clinic visits. Four had never gambled before starting dopamine agonist treatment. "Most of the time, the patient came in for a routine exam and would sheepishly admit 'I've been gambling too much,' or family members would mention that their loved one had been gambling excessively, that this behavior was totally out of character for them, and that the gambling was causing problems in their lives," says Dr. Dodd.
The researchers then assessed the relationship of the gambling behavior to the patients' medications. All were taking dopamine agonist medications at levels appropriate for Parkinson's treatment, and eight of the patients also were taking the drug carbidopa/levodopa. The researchers located existing case reports in medical literature associating Parkinson's disease treatment with pathological gambling, and they compared their patients' experiences with those reported in this literature. Dr. Ahlskog and colleagues then found that some of the patients stopped gambling when they discontinued use of the dopamine agonist.
They noted that in seven patients, pathological gambling developed within one to three months of reaching the maintenance dose or with dose escalation of dopamine agonist treatment; none developed pathological gambling while treated with carbidopa/levodopa alone. The other four patients reported compulsive gambling 12 to 30 months after starting dopamine agonist therapy; excessive gambling abated in all four within months of discontinuing the agonist medication.
"When our neurologists tapered the patients off the medication, several reported a dramatic resolution of their problem," says Dr. Dodd. "One patient said it was 'like a light switch going off.'"
The researchers also learned that six of the Mayo Clinic patients developed additional behavioral issues which subsided when they quit the dopamine agonist medication, including compulsive eating with weight gain, increased alcohol consumption and hypersexuality (increased interest in pornography, extramarital affairs or increased sex drive bothersome to the spouse).
Dr. Ahlskog cites anecdotes of patients such as a seemingly responsible, married professional who had never gambled before, but began watching gambling shows on television and then gambling on the Internet from his work site after starting dopamine agonist treatment. He lost several thousand dollars. This behavior abruptly stopped within a few days of stopping the dopamine agonist drug. A clergyman sheepishly confided by phone after an office visit that he had an obsession with gambling, which started after beginning a dopamine agonist medication. Another patient lost over $100,000 as well as her first marriage due to her compulsive gambling. She could never drive by a casino without going in, and each time she shopped for groceries, she was compelled to purchase multiple scratch-off lottery tickets.
Parkinson's patients have lower-than-normal levels of brain dopamine. The primary treatment for many years has been administration of levodopa (carbidopa/levodopa), which replenishes brain dopamine levels; this is considered to be the gold standard therapy for Parkinson's disease. Dopamine agonists are also used in Parkinson's disease treatment; they mimic the effect of dopamine in the brain. They are not as potent as levodopa, but produce a longer-lasting response. Dopamine agonist treatment is sometimes used by itself early in the course of Parkinson's disease or in addition to treatment with levodopa. The dopamine agonist drugs associated with pathological gambling appear to be those that specifically target the D3 dopamine receptors, according to Dr. Dodd. These receptors are located in the limbic system of the brain, which controls the emotions, affect and one's internal "reward system." When this area of the brain is overstimulated, it can lead to more impulsive behaviors and produce a feeling of pleasure from even a previously undesirable activity, such as compulsive gambling or alcohol consumption.
The Mayo Clinic researchers noted one type of dopamine agonist in particular continually surfaced as a treatment for the series' patients: pramipexole. They hypothesize this drug was implicated due to its strong stimulation of the brain's dopamine D3 receptors. A group of researchers at one medical center, including Erika Driver Dunckley, M.D., now a neurologist at Mayo Clinic, found pathological gambling in 1.5 percent of 529 Parkinson's patients treated with pramipexole in a retrospective study of all Parkinson's patients seen at the center over one year. This suggests that the problem does not occur frequently and that most people treated with pramipexole experience no such effect, according to Dr. Dodd.
Dr. Dodd explains that pathological gambling like that experienced by the Mayo Clinic patients analyzed can destroy a patient's and loved ones' quality of life. "Potentially, their financial reserves would be depleted, and they would neglect their social, occupational and family responsibilities in order to pursue gambling," she says. "It could lead them into financial ruin and contribute to broken relationships."
The Mayo Clinic researchers explain that because pathological gambling is so infrequently associated with dopamine agonist treatment, this potential side effect would not be a reason to stop prescribing it. Rather, they urge Parkinson's patients taking dopamine agonist medications to be very candid about gambling problems that may arise after starting the medication.
"I'd want patients to be very forthcoming with their doctors about their gambling," says Dr. Dodd. "If they or family members detect any behaviors that don't seem characteristic or that begin to stray from their usual behavior -- increased or problematic gambling, excessive eating or alcohol consumption -- they should bring it up to their neurologists. If you recognize this association early, you can possibly prevent financial ruin or destruction of relationships."
Dr. Ahlskog indicated he now tries to open the door for his Parkinson's patients to discuss gambling as a medication side effect by mentioning the potential when prescribing the medication and urging patients to tell him if they experience such effects. He also mentions the possible gambling issue with all new patients who are already taking a dopamine agonist. He emphasizes that pathological gambling linked to dopamine agonists is reversible as long as the association is recognized.
Although physicians frequently prescribe pramipexole for restless legs syndrome, the Mayo Clinic researchers believe the lower doses used pose little danger of it prompting pathological gambling.
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Journal
Archives of Neurology