Doctors now have an alternative in how they treat patients newly diagnosed with Parkinson's disease, according to a study in the October 18 issue of the Journal of the American Medical Association (JAMA). Besides levodopa, which for three decades has been the standard treatment for almost all new patients, the study found that doctors should also consider another type of drug known as a dopamine agonist.
"For 30 years the initial treatment of this disease has been straightforward," says Ira Shoulson, M.D., the University of Rochester neurologist who heads the Parkinson's Study Group, which conducted the study. "Now, there is a real choice that doctors and patients should be discussing."
Parkinson's patients have long faced a dilemma: Effective treatment of the disease eventually causes complications so severe that they can be worse than the disease itself. In this study of 301 patients at 22 study sites around the United States and Canada, doctors discovered that pramipexole, a medication known as a dopamine agonist, can offer a trade-off between side effects and treatment effectiveness that physicians and patients should consider.
The study was conducted by the Parkinson Study Group, an independent group of investigators at more than 65 academic institutions around North America led by physicians at the University of Rochester Medical Center. Patients were either treated with levodopa, the therapy that has been standard for three decades, or with pramipexole, a newer medication. The study was funded by Pharmacia Corp., which produces pramipexole, as well as the National Parkinson Foundation Center of Excellence and the National Institutes of Health.
Doctors followed the patients' progress for two years and found that patients treated initially with pramipexole instead of levodopa had fewer debilitating complications, including fewer involuntary movements and less wearing off of the medication. Yet pramipexole was not as effective as levodopa in controlling Parkinson's disease symptoms and was associated with more side effects, particularly sleepiness and hallucinations.
While the findings about the effectiveness of the medications are mixed, the bottom line is that patients and their doctors now have a choice of treatments that will depend on a patient's individual circumstances, says lead author Robert Holloway, M.D., a neurologist at the University of Rochester and first author of the study.
"Up to this time, levodopa has been the mainstay of therapy for Parkinson's patients," Holloway says. "We now have strong evidence that there are viable alternatives. We have options that will allow patients and families to make more informed decisions about what treatments are best for them."
In Parkinson's disease, a group of nerve cells in a particular region of the brain known as the substantia nigra degenerate and die. This results in many progressive symptoms that include slowness of movement, difficulty walking and swallowing, muscle stiffness, tremors, and rigidity. Approximately one million people in North America have the disease.
For three decades levodopa has been the first choice for patients just diagnosed with the disease. But levodopa carries with it potent side effects, most noticeably involuntary movements known as "dyskinesias," where a patient's arm, leg or hand moves suddenly and unpredictably. The longer a patient is on levodopa, the more likely such side effects become; eventually nearly all patients experience them.
"These involuntary movements can play havoc with a patient trying to live a normal life," says Holloway. Walking up stairs, brushing teeth, playing a musical instrument, writing a letter become difficult or even impossible. The movements are unpredictable, hindering patients' attempts to plan their activities.
In the study, patients treated with pramipexole developed these involuntary movements at only one-third the rate of patients treated with levodopa. Yet, though patients and doctors were pleased with the results from both drugs, pramipexole did not control the disease in its early stages as well as levodopa.
"There's a trade-off here that physicians and patients have to be aware of when deciding what therapy to begin," Holloway says. "Pramipexole clearly reduces the occurrence of developing abnormal motor movements, but levodopa is associated with better symptom control and less chance of sleepiness and hallucinations. It's a balance of adequately controlling the disease and the complications that often result from treatment."
In addition to pramipexole, other dopamine agonists on the market include ropinirole and older drugs such as pergolide and bromocriptine. The medicines are now used by doctors to help smooth out the highs and lows of motor control that many patients on levodopa experience. Other studies have shown that patients taking these drugs are also less likely to develop involuntary movements than patients on levodopa.
While the JAMA study helps clarify the initial effectiveness of pramipexole and levodopa, the authors note that several questions remain. For instance, the doctors are exploring whether the reductions in motor complications associated with pramipexole in this study will lead to long-term improvements in function and quality of life. Or, there may be subgroups of patients who can be identified who may respond better to one medication or the other. To help answer such questions, the Parkinson's Study Group is continuing the study for two more years.
Participating sites:
Albany Medical College, Albany, NY
Barrow Neurological Institute, Phoenix, AZ
Baylor College of Medicine, Houston, TX
Clinical Neuroscience Center, West Bloomfield, MI
Columbia-Presbyterian Medical Center, New York, NY
Massachusetts General Hospital, Boston, MA
McGill Centre for Studies in Aging, Montreal, Quebec
Ohio State University, Columbus, OH
Oregon Health Sciences University, Portland, OR
Ottawa Hospital Civic Site, Ottawa, Ontario
Saskatoon Dist. Health Board Royal University Hospital, Saskatoon, Saskatchewan
Toronto Western Hospital, University Health Network, Toronto, Ontario
University Hospitals of Cleveland, Cleveland, OH
University of Calgary, Calgary, Alberta
University of California, San Diego, San Diego, CA
University of Iowa, Iowa City, IA
University of Kansas Medical Center, Kansas City, KS
University of Rochester, Rochester, NY
University of Southern California, Los Angeles, CA
University of Tennessee-Memphis, Memphis, TN
University of Virginia , Charlottesville, VA
Yale University School of Medicine, New Haven, CT
Journal
JAMA