Compulsive gambling with extreme losses — in two cases, greater than $100,000 — by people without a prior history of gambling problems has been linked to a class of drugs commonly used to treat the neurological disorder restless legs syndrome (RLS). A new Mayo Clinic study is the first to describe this compulsive gambling in RLS patients who are being treated with medications that stimulate dopamine receptors in the brain. The Mayo Clinic report appeared in the current issue of Neurology.

The extent of this problem is unknown. Apparently, it occurs only in a small number of RLS patients treated with the pramipexole (Mirapex^®, Sifrol^®) or ropinirole (Requip^®). Considering this potential side effect of dopamine agonists, the Mayo Clinic authors suggest that physicians screen all RLS patients for compulsive behaviors while taking a thorough medical history prior to prescribing dopamine agonists. Patients should be monitored closely for signs of compulsive behaviors once dopamine agonist treatment has begun. The report suggests that the compulsion to gamble worsened with increasing doses of the dopamine agonists.

Pathological gambling is an impulse control disorder. In 2005, Mayo Clinic physicians reported this disorder as a side effect of dopamine agonist therapy in 11 Parkinson disease patients. "Although pathologic gambling has already been recognized in patients with Parkinson disease who often took high doses of dopamine agonists, the current report suggests that pathological gambling is not restricted to patients with Parkinson disease — and also can occur at low dosages" explains Maja Tippmann-Peikert, M.D., the lead author of the Mayo Clinic report on restless legs syndrome. "Physicians should not only monitor Parkinson disease patients for this behavior but also screen their RLS patients who may be on much lower doses of dopamine agonists." This includes encouraging the patient, family members and friends to report negative behaviors to the patient's physician.

Fortunately, pathological gambling seems to be reversible when the dose of the dopamine agonist is reduced or the patient is transitioned to an alternative medication. It is crucial that these adjustments are initiated before significant gambling debts develop, and relationships and careers are damaged.

This preliminary Mayo Clinic report is the first to link pathologic gambling to use of dopamine agonists in a disease other than Parkinson. It is based on the experience of three patients who have RLS. Their gambling problems were discovered during their medical evaluations at the Mayo Clinic Sleep Disorders Center. Although three patients is a small sample and larger studies are needed to validate these observations, the Mayo Clinic authors believe that the possible link between dopamine agonists and pathologic gambling behavior should be brought to physicians' attention immediately due to the social and financial consequences resulting from the behavior.

The Mayo Clinic neurologists found that gambling problems began, on average, about nine months after the patients began taking one of the two dopamine agonists. Speculation is that the gambling problems are emerging now because the newer generation of dopamine agonists — including pramipexole and ropinirole — are targeting receptors located in brain structures involved in motivation, emotion and reward behaviors. Researchers theorize that, in some people, such strong and specific stimulation in these neuronal pathways can prompt compulsive, pleasure-seeking behaviors such as pathological gambling.

Tippmann-Peikert M, Park JG, Boeve BF, Shepard JW, Silber MH.
Pathologic gambling in patients with restless legs syndrome treated with dopaminergic agonists.
Neurology. 2007 Jan 23;68(4):301-3.   [Abstract]