After starting drug therapy to treat her Parkinson's disease, a 59-year-old woman began stealing from her family to purchase large numbers of scratch-off tickets and to finance her 12-hour days of playing slot machines at the local casino. Now a new study confirms what anecdotal evidence has been saying all along: Dopamine receptor agonist drugs, in particular pramipexole and ropinirole, are linked to impulse control disorders, including gambling, hypersexuality, and compulsive shopping.

Dopamine is a neurotransmitter that affects the brain processes which regulate our movements, our emotions, and even our ability to experience pleasure and pain. Brain cells containing dopamine are clustered in a midbrain region called the substantia nigra. In Parkinson's disease, the dopamine-transmitting neurons in this area die, and as a result the brains of people with this disease contain practically no dopamine. Dopamine receptor agonist drugs have a structure very similar to the neurotransmitter, and so they bind to receptors in place of dopamine. They work, then, by directly stimulating the parts of the brain where dopamine normally functions.

Typically, doctors prescribe dopamine receptor agonist drugs to treat Parkinson's disease, though these same drugs are also used in cases of restless leg syndrome and hyperprolactinemia. However, since 2005, when psychiatrists at the Mayo Clinic published a study of 11 Parkinson's patients who developed a pathologic gambling habit after beginning treatment, many patients and their doctors have suspected these drugs may cause intense behavioral problems.

To understand whether any association between drugs and impulse control exists, a team of researchers analyzed domestic and foreign serious adverse drug event reports received by the FDA from 2003 to 2012. During the 10-year study period, the researchers identified 1,580 reports of pathological gambling, hypersexuality, compulsive shopping, and related impulse control disorders. The total included 710 events associated with dopamine receptor agonist drugs and 870 events for other drugs. Gambling was the most frequent impulse control behavior reported, with the term pathological gambling mentioned in 628 (40 percent) of the events, and gambling in 186 (12 percent). These were followed by hypersexuality, compulsive shopping, and poriomania.

The reports related to dopamine receptor agonist drugs occurred in patients with a median age of 55 years, where 65.8 percent of the patients were men. The drugs had been prescribed for Parkinson disease in 61.7 percent of the cases and restless leg syndrome in 23.8 percent. “Compared with dopamine receptor agonist drugs that were less selective, there was a stronger signal for agents with a preferential affinity for the dopamine D-3 receptor, notably pramipexole… and ropinirole,” noted the authors of the study, which focused on the drugs cabergoline, bromocriptine, rotigotine, and apomorphine.

A Revolutionary Drug

Dopamine receptor agonist drugs accounted for 2.1 million dispensed outpatient prescriptions in the final quarter of 2012. In a commentary appearing with the study, Drs. Howard D. Weiss and Gregory M. Pontone described how the discovery of dopamine deficiency and introduction of levodopa in the 1960s “revolutionized” neurology and neurotherapeutics. While the initial enthusiasm was dampened by fluctuations in patients’ levels of improvement and some unusual adverse effects, scientists developed a new class of pharmaceuticals, the dopamine receptor agonist drugs, over the ensuing years.

Unfortunately, “there were also scattered early reports of abnormal behaviors in patients receiving levodopa, particularly hypersexuality,” wrote Weiss and Pontone. They suggest the long period in which these side effects went unacknowledged may be due to the fact that both medical professionals and patients are accustomed to traditional side effects, such as dizziness, rash, or nausea, and less likely to understand or appreciate the role played by drugs in altering behavior.

“During an office visit, a patient is unlikely to spontaneously mention, ‘By the way, doctor, I lost $250 000 in casinos last year, and I purchase $500 of lottery tickets every week” or “I spend all night on Internet pornography sites and am soliciting prostitutes,’” wrote Weiss and Pontone.

Sources: Moore TJ, Glenmullen J, Mattison DR. Reports of Pathological Gambling, Hypersexuality, and Compulsive Shopping Associated With Dopamine Receptor Agonist Drugs. JAMA. 2014.

Weiss HD, Pontone GM. Dopamine Receptor Agonist Drugs and Impulse Control Disorders. JAMA. 2014.