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News in Brief
Parkinson's Drug May Cause Problems with Impulse Control
A study from the Mayo Clinic appearing in the July 11 issue of Archives of Neurology described the development of pathological gambling in 11 patients who were taking dopamine agonists. Since the study concluded, investigators identified 14 additional patients on dopamine agonists who say that they too encountered problems with gambling after taking these medications. The majority of patients were taking pramipexole (Mirapex®), but all commonly-prescribed dopamine agonists have been associated with pathological gambling.
Dopamine agonists are medications used to mimic dopamine in the brain by stimulating dopamine receptors. Pramipexole, ropinirole and pergolide are the most commonly-used drugs for Parkinson's to treat tremor and stiffness. They also interact with dopamine receptors in the brain (systems involved with emotions such as pleasure and gratification).
The Mayo Clinic findings coincide with a 2003 study published by investigators at Duke University Medical Center that suggested a link between high doses of dopamine agonists and the development of impulse-control disorders.
In response to reports of this phenomenon, Pfizer and Boehringer Ingelheim Pharmaceuticals, the manufacturer and the distributor of Mirapex®, revised their drug's package insert earlier this year to include pathological gambling as a potential adverse reaction reported after the drug was approved. However, according to The Associated Press, Boehringer Ingelheim has stated that there has not been sufficient scientific evidence to prove that Mirapex® is associated with gambling or other uncontrolled behaviors.
As part of their routine care, doctors at the Mayo Clinic are now asking patients who use dopamine agonists if they have developed a problem with gambling. The doctors report that adjustments in dosage or changes in the medication type seem to alleviate the problem.
"While rare in frequency relative to conditions such as depression and anxiety in Parkinson's patients, pathological gambling and other problems with impulse control can develop in association with any type of antiparkinsonian treatment," said Dr. Laura Marsh, Associate Professor of Psychiatry and Neurology at Johns Hopkins University School of Medicine. "However, there appears to be a particular association with the use of dopamine agonists. It is not known why certain individuals may be more vulnerable to this adverse effect. Until that information is available, it is important for clinicians, patients and families to be aware of the potential for behavioral changes and respond to them immediately."
For more information on Parkinson's disease and impulse-control disorders, contact PDF at (800) 457-6676 to request Dr. Marsh's article, Gambling, Sex, and…PD?, featured in our spring 2005 newsletter.
UK Experts Find Evidence of GDNF's Effects
Researchers at Frenchay Hospital in Bristol, UK, have found scientific evidence for the first time that the infusion of glial cell line-derived neurotrophic factor (GDNF) directly into the brain of a patient with Parkinson's disease may induce the re-growth of dopamine nerve fibers. This information, published in the July 1 issue of Nature Medicine, was discovered through an autopsy of a 62-year-old man who had been involved in a GDNF Phase I study, and who died of a heart attack in December.
GDNF is a nerve growth factor that supports and promotes the development of dopamine cells in the brain. Because Parkinson's disease results from the loss of dopamine cells, scientists have attempted to deliver this growth factor directly into the brains of patients. In the clinical trial, participants received an infusion of GDNF through a catheter directly to a part of the brain called the putamen. The autopsy of the former study participant, who received GDNF to the right side of his brain, revealed sprouting of nerve fibers in the vicinity of the catheter tip. According to the autopsy, the dopamine fibers infused with GDNF occupied an area five times larger than corresponding fibers on the other side of the brain, which had not received GDNF treatment. The researchers state that the increase in dopamine fibers was linked to this patient's sustained clinical benefit and the improved dopamine imaging studies that had been performed during the trial.
This information comes on the heels of two lawsuits brought against Amgen, the manufacturer of GDNF, by patients who participated in GDNF trials in New York and Kentucky. Amgen halted clinical trials of this drug in August 2004 due to safety concerns. A number of the trial participants insist that the drug was helping their symptoms, and many investigators feel that the safety concerns raised by Amgen regarding lesions found in monkeys were not due to toxicity of the drug. In both cases, judges ruled that Amgen was not required to continue distributing GDNF to trial participants.
GDNF lies at the intersection of scientific research, corporate interests and the aspirations of the PD community. Within the PD community there remains hope that GDNF research will yield a treatment for the disease. Although GDNF has been shown to promote dopamine cell growth and repair in animal models, clinical trials in humans have not met the expectations of scientists. The current case report, which for the first time describes dopamine nerve cell sprouting in a patient with PD, adds intriguing data to the GDNF story.