SAN DIEGO—Since their introduction more than a decade ago, dopamine agonists have played an increasingly significant role as an adjunct to levodopa therapy for Parkinson’s disease. But new studies show that for a small fraction of patients, this therapy comes with a price: an increased risk of pathologic gambling, excessive shopping, and hypersexuality. The latest insights into these behaviors were front and center at the 58th Annual Meeting of the American Academy of Neurology.

RISK FOR PATHOLOGIC GAMBLING IS SIGNIFICANT

Of the 297 patients completing the surveys, approximately 6% reported one or more types of compulsive behaviors—primarily, pathologic gambling, defined as an irresistible urge to gamble despite severe personal and financial consequences. The expected prevalence of pathologic gambling in the general population is only 1% to 2%, Dr. Voon said. The group of gamblers included comparable numbers of men and women. They preferred slot machines to more interactive types of gambling, such as playing cards. They had lost an average of $100,000 each, and several had marriages in crisis as a result of the behavior.

In all, 16% of patients receiving levodopa and an adjunctive dopamine agonist developed one or more compulsive behaviors. No particular agent was implicated more than another. No patients in the sample who were on levodopa monotherapy were compulsive gamblers.

Similar results were found for hypersexuality (affecting seven patients) and compulsive shopping (affecting two), although the normal prevalence of these behaviors is not well enough established to determine how far outside the norm the prevalence in this sample was.

Compared to nonaffected controls with Parkinson’s disease, the compulsive gamblers were more likely to have an elevated novelty-seeking score, a higher impulsivity score, a younger Parkinson’s disease onset, and a personal or family history of alcohol use disorder. "Certainly the vast majority of patients do well on these medications," Dr. Voon commented, "but patients, caregivers, and clinicians should be aware of these behaviors."

A CLASS EFFECT

"Pathologic gambling has been traditionally defined as an impulse control disorder," according to Oksana Suchowersky, MD, Professor of Neurology and Medical Genetics at the University of Calgary, Alberta, who conducted a second study of this problem. "However, there is increasing evidence that pathologic gambling has much more in common with addiction." Little is known about the physiology of gambling, but it appears to be related to the dopaminergic system and its projections to the limbic system and nucleus accumbens—key reward centers. fMRI differences have been seen in the brains of pathologic gamblers versus controls.

Dr. Suchowersky’s study of almost 200 patients with Parkinson’s disease echoed the findings from Dr. Voon’s report. She found that approximately 6% of all Parkinson’s disease patients exhibited pathologic gambling. All of the affected patients were receiving dopamine agonists together with levodopa; no patient on levodopa monotherapy had the disorder. All the patients who developed a problem began as recreational gamblers. No single dopamine agonist was to blame: "We feel the problem of gambling is a class effect," she said.

Among patients in her study, six switched to an alternative dopamine agonist, two decreased the dose, four discontinued altogether, and three continued medication therapy with counseling.

It is critical to talk with patients about this possible complication of therapy before starting a dopamine agonist, Dr. Suchowersky said, and to monitor for it throughout the course of therapy. Family members also need to be informed, as there is often denial or lack of insight on the part of patients about the existence of, or background for, compulsive behaviors.

COMPULSIVE CONTEXT

Dr. Suchowersky also pointed out that screening for compulsive behaviors may be appropriate in other disorders in which dopamine agonists are used, such as restless legs syndrome. "I am mentioning it now to my restless legs syndrome patients," she said.

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