MIAMI BEACH — Levodopa produces greater symptomatic relief for Parkinson's disease patients, compared with a dopamine agonist, consistent results of long-term studies indicate, but 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?
Use patient age as a general guide. Prescribe levodopa for older and dopamine agonists for younger patients. However, “we shouldn't be firmly stating use of a dopamine agonist or levodopa. We are individualizing therapy,” she said.
In the Comparison of the Agonist Pramipexole With Levodopa on Motor Complications of Parkinson's Disease study, Dr. Waters, professor of clinical neurology at Columbia University Medical Center, New York, and her colleagues randomized 151 patients to pramipexole and 150 others to levodopa in 1996 and 1997. The patients 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 had 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.
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 (Permax) 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 Pergolide was withdrawn from the U.S. market in 2007 because of its potential for heart valve damage.
There was a significant delay 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. The authors concluded that both agents are suitable for initial therapy, so physician judgment drives the decision based on efficacy and adverse events.
Dr. Waters also addressed the 10-year results of a ropinirole (Requip) 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.
At 10 years, 51 patients remained in the ropinirole cohort and 29 in the levodopa group. “Even after the 10 years, there was a substantial difference in those being free of dyskinesia for those initially randomized to ropinirole [52%] versus levodopa [77%],” Dr. Waters said.
“These clinical trials are all quite consistent,” she said. “Dyskinesia is better with dopamine agonists and the [symptomatic] effect of levodopa is greater.”
Disclosures: Dr. Waters is on the advisory board or speakers bureau of Boehringher Ingelheim, GlaxoSmithKline, Novartis, and Teva.