New Parkinson's Guidelines: Save Levodopa for Later
June 11, 2001 -- Levodopa has ended its 30-year reign as the first-line drug for the treatment of symptomatic Parkinson's disease.
Even after all this time, levodopa still is considered the most effective Parkinson's treatment. But new treatment guidelines, announced in a special issue of Neurology, the official journal of the American Academy of Neurology, now advise doctors to withhold levodopa treatment until newer drugs have lost their effect.
"The big change is what drug to use first," says William C. Koller, MD, PhD, director of the Parkinson's disease center at the University of Miami and co-author of the new guidelines. "If patients' symptoms can be controlled initially and they have fewer side effects, this is the key issue. Because unfortunately, Parkinson's disease is progressive, and the drugs we give today have a profound effect on what happens later. We really have to be thinking ahead when treating patients with Parkinson's disease."
Parkinson's disease occurs when brain cells that make an important brain chemical -- dopamine -- slowly die off. Starved of dopamine, the part of the brain that controls movement stops working properly. One of the greatest breakthroughs in medical history occurred when researchers found a compound -- levodopa -- that could enter the brain and turn into dopamine.
"When we first had levodopa, in the early 1970s, we doctors naively increased the dose as much as possible," Koller says. "But two or three years later these patients developed a whole host of side effects. Then we learned to use lower doses."
Even with lower doses, however, levodopa gradually begins to cause wide swings in brain levels of dopamine. The problem goes from too little movement to too much, unwanted movement. Eventually -- usually after about five years -- levodopa loses its ability to help.
Newer drugs work differently by mimicking the action of dopamine in the brain. These so-called dopamine agonists include Permax, Mirapex, Requip, and Parlodel (although Koller says this last, older agent is used only infrequently).
New clinical studies show that these new agents work as well as levodopa as a first-line agent -- with fewer side effects. The new guidelines advise doctors to try them first -- and as they slowly lose their effect, their dosage can be increased. When maximum dosage is reached, the guidelines advise that levodopa can be added. Other drugs can be added to help control side effects.
"The key issue is when we see a patient in the clinic we want to make that patient well now, and make sure 10 years from now that the patient is doing just as well," Koller says. "That is why the new change is such a key shift."
There is also some evidence that the new dopamine agonists may actually protect the brain against the ravages of Parkinson's disease. On the other hand, these drugs can make a person sleepy -- with onsets so sudden that some doctors have called them "sleep attacks."
The new guidelines reflect changes already under way in clinical practice, according to Lori McGee-Minnich, RN, a research instructor at the University of Washington movement disorder clinic in St. Louis.
"It's not rocking the neurological world," McGee-Minnich tells WebMD. "A number of patients tend to be started on a dopamine agonist, but some physicians will start with low-dose levodopa first. As we put out more new neurologists each year, they tend to lean more toward the dopamine agonists as the first-line treatment."