News

Dopamine Agonists Quell Dyskinesia in PD


 

Major Findings: At 6 years, 50% of trial participants started on pramipexole and 69% started on levodopa experienced motor complications.

Data Source: A randomized trial of 151 patients initially assigned to pramipexole and 150 others assigned to levodopa in 1996 and 1997.

Disclosures: The presenter is on the Novartis and Teva advisory boards and Boehringher Ingelheim, GlaxoSmithKline, Novartis, and Teva speakers bureaus.

MIAMI BEACH – Levodopa produces greater symptomatic relief for Parkinson's disease patients compared with a dopamine agonist, consistent results of long-term studies indicate. However, more dyskinesia and motor fluctuations are the trade-offs.

Dopamine agonists are still effective treatments for Parkinson's disease, said Dr. Cheryl Waters at the World Federation of Neurology World Congress on Parkinson's Disease and Related Disorders. So how do you choose one or the other for initial therapy?

Generally, use patient age as a general guide. Prescribe levodopa for older and dopamine agonists for younger patients.

In the Comparison of the Agonist Pramipexole With Levodopa on Motor Complications of Parkinson's Disease, Dr. Waters, professor of clinical neurology at Columbia University Medical Center in New York City, and her colleagues randomized 151 patients to pramipexole, and 150 others to levodopa in 1996 and 1997. The participants were permitted to switch to levodopa during an open-label phase. Six-year results for 222 participants showed that 50% of the initial pramipexole group and 69% of the initial levodopa group experienced motor complications (Arch. Neurol. 2009;66:563-70).

By the final visit, dyskinesias were more common in the initial levodopa group than in the initial pramipexole group (37% vs. 20%, respectively), Dr. Waters said. “Those in the pramipexole group have substantially remained on pramipexole all these years, even though they are not in the trial anymore,” she noted.

Dr. Waters also referred to the Pergolide versus L-Dopa Monotherapy and Positron Emission Tomography (PELMOPET) trial, in which 148 early Parkinson's disease patients were randomized to pergolide and another 146 to levodopa in this 3-year, multicenter, double-blind study (Mov. Disord. 2006;21:343-53). Pergolide was withdrawn from the U.S. market in 2007 because of its potential for heart valve damage.

A significant delay was found in the onset of dyskinesia and lower severity of motor symptoms in the pergolide group, Dr. Waters said. The levodopa group, however, reported significantly greater symptomatic relief on the Unified Parkinson's Disease Rating Scale (UPDRS) sections I, II, and III; Clinical Global Impressions severity and improvement ratings; and the Patient Global Impressions improvement scale.

The authors concluded that both agents are suitable for initial therapy, so physician judgment drives the ultimate decision based on efficacy and adverse events.

Dr. Waters also addressed the 10-year results of a ropinirole versus levodopa study (Mov. Disord. 2007;22:2409-17).

This was an extension of a study that compared treatment with ropinirole in 85 patients with levodopa therapy in 45 patients at 5 years (N. Engl. J. Med. 2000;342:1484-91). At that time point, the cumulative incidence of dyskinesia was 20% with ropinirole, compared with 45% with levodopa.

“These clinical trials are all quite consistent,” Dr. Waters said. “Dyskinesia is better with dopamine agonists and the [symptomatic] effect of levodopa is greater.”

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