Reasonable Options for Initial Treatment of Parkinson Disease

The drugs levodopa and pramipexole both appear to be reasonable options as initial therapy for Parkinson disease, but they are associated with different efficacy and adverse effects, according to an article in the July issue of The Archives of Neurology, one of the JAMA/Archives journals.

Parkinson disease is a progressive neurologic disease. It is believed to be related to low levels of the important neurotransmitter (messenger) dopamine in certain parts of the brain. When the drug levodopa is taken orally, it crosses through the “blood-brain barrier” and is converted to dopamine. Another drug, carbidopa, is added to levodopa to prevent the breakdown of levodopa before it crosses into the brain. Pramipexole is one of several drugs that mimic the role of dopamine in the brain, causing the neurons to react as they would to dopamine.

The Parkinson Study Group conducted a multicenter, parallel-group, double-blind, randomized controlled trial to compare initial treatment with pramipexole vs. levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of motor complications, other adverse events, and functional and quality of life outcomes. Robert G. Holloway, M.D., M.P.H., of the University of Rochester, Rochester, N.Y., and colleagues reported the results for the Parkinson Study Group.

Patients with early Parkinson disease who required dopaminergic therapy (relating to nerve cells or fibers that employ dopamine as their neurotransmitter) to treat emerging disability enrolled in the study between October 1996 and August 1997. Among 301 patients, 151 were randomly assigned to receive 0.5 milligrams of pramipexole three times per day with levodopa placebo. The other 150 patients received 25/100 milligrams of carbidopa/levodopa three times per day with pramipexole placebo. Dosage was escalated during the first ten weeks for patients with ongoing disability. After that, the investigators were permitted to add open-label levodopa or other anti-Parkinsonian medications to treat ongoing or emerging disability. The patients were observed until August 2001.

“Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias [uncontrollable body movements; 24.5 percent vs. 54 percent with initial treatment with levodopa] and wearing off [47 percent vs. 62.7 percent with initial treatment with levodopa],” the authors write.

Initial levodopa treatment resulted in a significant reduction in the risk of “freezing” of motor function [25.3 percent vs. 37.1 percent with initial treatment with pramipexole], the researchers report.

Initial treatment with levodopa also resulted in lower incidences of somnolence (sleepiness; 36 percent vs. 21 percent), and edema (excess fluid in the tissues; 42 percent vs. 15 percent) and provided for better symptomatic control, as measured by the Unified Parkinson Disease Rating Scale.

By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the two groups. Both options resulted in similar quality of life.

“Pramipexole and levodopa are associated with different efficacy and adverse-effect profiles. These differences are insufficient to identify a preferred strategy; hence, both pramipexole and levodopa appear to be reasonable options as initial dopaminergic therapy in Parkinson disease,” the authors conclude.

“Long-term follow-up is needed to determine if either treatment strategy is superior to the other in terms of patient impairment, disability, or quality of life,” they write.