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October 29, 2014
Stronger Link Between Dopamine Receptor Agonists, Impulse-Control Disorders

Alexandria, VA—New research provides more evidence of a strong link between use of dopamine receptor agonist drugs—most often prescribed for Parkinson’s disease, restless leg syndrome and hyperprolactinemia—and impulse-control disorders such as pathological gambling, hypersexuality, and compulsive shopping.

The study found that during a 10-year period, 1,580 adverse drug events were reported in the United States and 21 other countries, indicating impulse-control disorders in patients, including 628 cases of pathological gambling, 465 cases of hypersexuality, and 202 cases of compulsive shopping. Dopamine receptor agonists accounted for 710 of the events, compared to 870 events for other drugs.

“Our findings confirm and extend the evidence that dopamine receptor agonist drugs are associated with serious impulse control disorders; the associations were significant, the magnitude of the effects was large and the effects were seen for all six dopamine receptor agonist drugs,” according to the report published recently in JAMA Internal Medicine.

Study authors, led by Thomas J. Moore of the Institute for Safe Medication Practices in Alexandria, Virginia, point out, “At present, none of the dopamine receptor agonist drugs approved by the FDA have boxed warnings about the potential for the development of severe impulse control disorders as part of their prescribing information. Our data, and data from prior studies, show the need for these prominent warnings.”

Background in the report notes that 2.1 million dopamine receptor agonist prescriptions were dispensed in the fourth quarter of 2012.

For the study, the authors analyzed adverse drug event reports from 2003 to 2012 for six dopamine receptor agonist drugs marketed in the United States, using 2.7 million domestic and foreign adverse drug event reports from the FDA’s Adverse Event Reporting System database.

The 710 reports for dopamine receptor agonist drugs, representing 44.9% of the total, occurred mostly among males, 64.8%, with a median age of 55 years. About half of the adverse reactions occurred in the United States. Parkinson’s disease was the most common diagnosis in those patients, 61.7%, followed by restless leg syndrome, 23.8%.

In a related commentary, Joshua J. Gagne, PharmD, ScD, of Brigham and Women’s Hospital and Harvard Medical School in Boston calls the research “compelling.”

“The authors used these data to calculate a proportional reporting ratio (PRR) of 277.6, indicating that the proportion of all adverse event reports involving impulsive behavior was 277.6 times higher for dopamine receptor agonist drugs vs. other drugs,” Gagne notes.

“Given the limitations of FAERS [U.S. Food and Drug Administration’s Adverse Event Reporting System database] and the provocative analysis by Moore and colleagues, is the association between dopamine receptor agonist drugs and impulse control disorders likely a true causal connection and not merely a pattern among random data? With the large PRR [proportional reporting ratio] that may actually be attenuated by confounding and the emerging evidence from other sources, the likelihood of a causal connection is high,” he concludes.

In another commentary, Howard D. Weiss, MD, of Sinai Hospital of Baltimore, and Gregory M. Pontone, MD, of Johns Hopkins University School of Medicine, write that the report “highlights the associations between impulse control disorders and dopamine receptor agonist drugs.”

“The report raises several questions: How do dopamine receptor agonist drugs trigger the abnormal behaviors seen in patients with impulse control disorders? Why do some patients, but not others, develop these problems? Why was the association not recognized sooner?” Weiss and Pontone add.

“In summary, physicians have overestimated the benefit and underestimated the risks associated with the use of dopamine receptor agonist drugs in patients with Parkinson disease,” the commentators conclude. “In our view, these medications should be used less frequently and with great caution, paying close attention to possible untoward effects on behavior and impulse control.”

U.S. Pharmacist Social Connect