Study findings may change standard Parkinson's therapy

Drug comparisons foreshadow a rethinking of the approach to early-stage treatment.

By Victoria Stagg Elliott, amednews staff. June 5, 2000.

Recent findings regarding the treatment of Parkinson's could have a dramatic effect on how physicians care for patients in early stages of the disease.

Specifically, a study released last month concluded that dopamine agonists may be more effective in treating Parkinson's disease while causing fewer adverse side effects than the current standard drug, levodopa.

New approach for early-stage Parkinson's?

However, dopamine agonists are more than twice as expensive as levodopa and take more of a physician's time to administer. Yet they also hold out the hope of a higher quality of life for a longer period of time and the potential to delay or eliminate the need for high-risk brain surgery -- often a patient's last resort in the fight against the progressive neurological disorder.

The drugs are particularly promising for young patients in the early stages who have much longer to live with the disease and the therapy.

According to a study published in the May 18 New England Journal of Medicine, the use of levodopa, long considered a miracle drug for patients with Parkinson's, should not be discarded, but rather delayed.

"[This study] demonstrates unequivocally ... that if you start patients with a dopamine agonist such as ropinirole and supplement them with levodopa when the ropinirole alone can no longer provide satisfactory clinical control, you end up with comparable benefits with dramatically reduced instance of intolerable adverse events," Warren Olanow, MD, chair of neurology at Mount Sinai School of Medicine, New York, said at a news conference last month announcing the recent findings. "This is a major step forward for all people who suffer from Parkinson's disease."

Postponing progression

For the past 30 years, levodopa has been the No. 1 choice for treating Parkinson's disease. However, it has one big drawback: Eventually it stops working. Over time, the amount of the drug once necessary to provide hours of relief remains effective for as little as 30 minutes.

This dopamine-replacer also causes increasingly severe side effects that some patients say are worse than the disease, most notably dyskinesia. Thus, doctors and researchers have been looking at ways to delay the need for the drug.

Dopamine agonists first started being used in 1980 but only as a late-stage addition to alleviate the adverse affects of levodopa. Animal studies then indicated that the family of drugs might be better as a starting point therapy.

Dr. Olanow estimates that 15% to 20% of early-stage Parkinson's patients currently rely primarily on dopamine agonists, as a result of smaller studies published during the past couple of years in less-mainstream journals.

"My prediction is that in five years more than 50% of early Parkinson's disease patients will be treated precisely as suggested in this article," he said.

Specifically, the study followed nearly 300 patients in 30 different locations around the world. Half took the traditional levodopa treatment. The others took Requip, the form of ropinirole hydrochloride manufactured by SmithKline Beecham. Levodopa was added to this arm as a supplement if necessary.

After five years, both groups were similar in their parkinsonian symptoms, but the group that started with the dopamine agonist had a three times lower incidence of dyskinesia.

This news is particularly relevant to how physicians treat younger patients with Parkinson's.

"If you are 70, you could do well on levodopa for five or six years and live out your life," said Abraham Lieberman, MD, medical director of the National Parkinson Foundation. But the reality that younger patients have much longer to live with the disease has contributed to the impetus to improve available therapies.

"The philosophy of treatment has changed, and we tend to use the dopamine agonists more now initially when we start treatment," said James Tetrud, MD, medical director of the Parkinson's Institute in Sunnyvale, Calif., who has been treating the disease for 20 years.

Doctors also now have more than one drug from which to choose. "The controversy used to be: Should we treat symptoms as soon as they appear or should we wait until significant disability?" said Jeanne Rosner, associate director of education for the Parkinson Disease Foundation. "Now, it's turning to whether to begin with Sinemet [levodopa plus the inhibitor carbidopa] therapy or agonist therapy as a way of delaying or even eliminating the long-term effects of Sinemet use. Things are changing."

But with change comes challenges.

Dopamine agonists, for example, are more time-consuming to prescribe. "With managed care, primary physicians and neurologists have less time to see the patient and so it's a lot easier for them to use l-dopa, which is very effective and the benefit is almost immediate," said Dr. Tetrud. "Using a dopamine agonist does take a bit of time." He usually gives patients a four- to six-week schedule to initiate themselves to the drug and has them call in at the end of an agreed period.

The drug is also more expensive. A year of levodopa, a generic drug, costs an average of $750. A year of Requip costs about $2,000. However, Dr. Lieberman said that expense is offset by the reduced likelihood of the patient having to undergo expensive surgery.

"If in five years you need a $30,000 operation with a great complication rate, the translation is that it's probably better economically" to take the dopamine agonist, he said.

ADDITIONAL INFORMATION:

New approach for early-stage Parkinson's?

A recent study compared the effectiveness of newer dopamine agonists, such as ropinirole, with the current standard, levodopa, in delaying onset of more severe Parkinson's symptoms, reducing adverse drug affects and minimizing the need for high-risk brain surgery.

Participants: A total of 268 patients with early-stage Parkinson's in 30 centers in Europe, Israel and Canada.

Length of study: Five years.

Results: 34% of patients in the ropinirole group did not require levodopa during the study; 64%of those who started with levodopa required an increase in dosage. The rate of dyskinesia after five years was 20% in the ropinirole group and 45% in the levodopa group.

Findings: Early Parkinson's can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with a dopamine agonist alone and supplementing with levodopa if necessary.

Source: New England Journal of Medicine, May 18