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 patients with PD. 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.
Patients with PD who are taking dopamine(Drug information on 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 patients with PD 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. To be sure, the occasional patient with PD who receives dopamine agonists begins to engage in other activities--often familiar ones--with increased intensity. Dodd recalled a patient who began fishing more often than usual. Friedman spoke of a patient who began nonstop comparison-shopping. The patient didn't buy anything; she just went about comparing prices. But pathologic gambling, rare as it is, does stand out as the complex behavior most likely to be precipitated by dopamine agonists.
Triggering D3 receptors
Dodd speculated that stimulation of D3 receptors in the nucleus accumbens plays a role in pathologic gambling. She pointed out that the nucleus accumbens, an integral part of the pleasure/reward circuit, is rich in D3 receptors and that pramipexole(Drug information on pramipexole) is highly selective for the D3 receptor and has a greater affinity than other dopamine agonists for that receptor.
In her case series, most patients (82%) were receiving pramipexole, as were the majority of patients (59%) in previously published reports. Along the same lines, a retrospective study of 1884 patients with PD found that 8 (1.5%) of 529 who took pramipexole, but only 1 (0.3%) of 331 who took pergolide(Drug information on pergolide) (Permax), engaged in pathologic gambling.3 No patients who received levodopa(Drug information on levodopa) alone or ropinirole(Drug information on ropinirole) engaged in excessive gambling. Seven patients started gambling within 1 month of having their dopamine agonist dosage increased; 6 patients stopped after their therapy was switched to ropinirole.
Jon Grant, MD, JD, an associate professor of psychiatry at the University of Minnesota, is an expert on so-called impulse-control disorders, including pathologic gambling. He has found the relationship between dopamine agonist treatment and pathologic gambling "truly bewildering." Going along with the D3 receptor-nucleus accumbens theory, he suggested that a dopamine agonist might well cause a problem with any type of rewarding behavior. But why pathologic gambling? To Grant, it would make more sense for a dopamine agonist to trigger compulsive shopping or hypersexuality. He wondered whether the patients with PD who become pathologic gamblers are prone to addictive behaviors. "Are they genetically vulnerable to addiction?" he asked. "Have they minimized previous addiction?"
Pathologic gambling appears to occur rarely in patients with PD. In fact, the prevalence of such behavior may be no greater in patients with PD than in the general population. The prevalence of pathologic gambling in the retrospective study was 0.05%,3 whereas in the general population, it averages 1.6%.6 Rare as it is, however, pathologic gambling may occur more frequently in patients with PD than clinical impression and the existing data suggest; patients seldom report this behavior--the majority of published cases came to light because concerned relatives spoke out about the patient's behavior. A proper prevalence study remains to be done.
The prevalence of pathologic gambling in patients with PD may not be greater, but the condition in these patients differs substantially from that in the general population. The link to dopamine agonist treatment seems clear, and the abrupt onset and resolution with cessation of the offending agonist are unique features.