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Dopamine Agonists, Pathologic Gambling, and Parkinson Disease: A Connection?

Dopamine Agonists, Pathologic Gambling, and Parkinson Disease: A Connection?

Parkinson disease (PD) patients treated with dopamine receptor agonists are prey to a number of symptoms over and above classic motor disturbances. Some of the common symptoms-dyskinesia, nausea, and hallucinations-are more or less foreseeable consequences of excessive dopamine stimulation and are justifiably perceived as adverse effects of therapy. Other symptoms-confusion, depression, and punding-are more difficult to account for. They may be a result of the disease, its treatment, or both. Over the past 5 years, case reports and series have noted the onset of pathologic gambling in PD patients treated with levodopa and dopamine agonists.1-4

The case reports have named dopamine receptor agonists as the likely culprits, but the role of levodopa has been unclear and the possibility that the symptom is a manifestation of PD itself has been posited.5 In the September 2005 issue of Archives of Neurology, a team headed by Maryellen Dodd, MD, a psychiatrist at the Mayo Clinic, wrote about 11 patients with PD in whom pathologic gambling developed.4 In all cases, the gambling behavior arose after the beginning of treatment with dopamine agonists. In the 8 patients for whom follow-up information was available, the gambling abruptly stopped when the dopamine agonist was tapered or discontinued. Pathologic gambling did not develop in any of the patients who were receiving levodopa alone, and 3 of the pathologic gamblers had not received levodopa. Pramipexole (Mirapex, Boehringer Ingelheim) was the agonist taken by 9 of the 11 patients studied.

The findings presented by Dodd and colleagues provide persuasive evidence that treatment with dopamine agonists, particularly pramipexole, can precipitate pathologic gambling. Dodd noted that this effect might not be limited to Parkinson patients. Since publication of the article in Archives of Neurology, she has learned of people who became pathologic gamblers after being treated with ropinirole (Requip, GlaxoSmithKline) for restless legs syndrome. The idea that pathologic gambling-ie, uncontrollable gambling that typically results in personal, legal, and financial trouble-can be precipitated by drug therapy challenges conventional views about complex behaviors and the effects that drugs can have.

The novice pathologic gambler (many of the PD patients given to pathologic gambling had never gambled before) suddenly acquires the desire to gamble, locates a casino, gets hold of some money, chooses a game, plays the game, and deceives others about what he or she is up to. It's hard to imagine how behavior this specific and complex can be caused by a dopamine agonist. "I don't understand it," said Joseph Friedman, MD, a neurologist in Warwick, RI, "but it's real; it's really real." Friedman has seen about 10 PD patients who began gambling excessively while receiving dopamine agonists.

One of the features of this behavior that intrigues Friedman is that unlike other behavioral effects of Parkinson treatment such as punding, patients who are pathologic gamblers don't find their behavior strange. Even if they've never gambled before, they suddenly have an urge to gamble. They don't link the compulsion with drug therapy, they don't view it as a problem, and they don't discuss it, according to Friedman. "You have to ask about it," he said.

MANIA OR COMPULSIVITY?

Excessive gambling is a well-known feature of mania. Drugs that enhance dopamine stimulation-levodopa in particular-are known to bring on manic episodes in vulnerable patients. So one plausible explanation for pathologic gambling in PD patients is that the gambling is a symptom of mania. Six of Dodd's 11 patients experienced additional behavioral symptoms along with the pathologic gambling, some of which are symptoms of mania (eg, increased spending, hypersexuality, increased alcohol consumption). For 5 of the patients, though, pathologic gambling occurred in isolation.

Dodd pointed out that the study patients underwent thorough psychiatric evaluation and none met the criteria for a manic syndrome. She doesn't believe that mania or hypomania explains the pathologic gambling seen in PD patients. Friedman agreed. The pathologic gamblers he has come across have not had concurrent hypersexuality or other manic symptoms. In his experience, pathologic gambling turns up on its own. Parkinson patients treated with dopamine agonists occasionally handle, sort, and arrange objects incessantly. This behavioral pattern, known as punding, is attributed to dopamine stimulation.

Could pathologic gambling be a variant of this repetitive, driven behavior? Probably not. Unlike pathologic gamblers, who typically see nothing amiss, patients with punding usually recognize the behavior as odd. Whereas pathologic gambling involves the orchestration of thinking, desire, and behavior, punding is primarily repetitive motor activity. What's most intriguing about the pathologic gambling seen in PD patients is not that these patients suddenly take on a new activity, but the activity itself. The patients aren't beset with a desire to smoke cigars, drink tequila, or play the piano. They want to gamble.

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