Pramipexole is a full dopamine agonist that has strong specificity for D3 receptors of the D2 receptor family. A previous study showed that this agent decreased the amount of time patients had symptoms of Parkinson's disease and improved motor function among patients with advanced disease treated with levodopa. The Parkinson Study Group evaluated the safety and efficacy of four doses of pramipexole in patients with early Parkinson's disease.
A total of 264 patients with Parkinson's disease entered the placebo-controlled, randomized study. Patients had had Parkinson's disease for no more than seven years and were classified as having stage I, stage II or stage III disease. Amantadine, selegiline and anti-cholinergic medications were permitted during the study period, but none of the patients was receiving other dopamine agonists. Exclusion criteria were dementia, atypical parkinsonism or severe illness. Patients under 30 years of age and those who had taken antipsychotic medications in the previous six months were also excluded.
Patients were randomized to receive either placebo or pramipexole in a daily dosage of 1.5 mg, 3.0 mg, 4.5 mg or 6.0 mg in three divided doses. Patients were seen at baseline and then at two, four, six, eight, 10 and 11 weeks after baseline. Unified Parkinson Disease Rating Scale (UPDRS) scores and the occurrence of adverse events were determined at each follow-up visit. Specific outcomes measured in the study included how well the drug was tolerated and the change in the UPDRS score between baseline and 10 weeks of treatment.
Nearly all of the placebo group (98 percent) completed the study, compared with 81 percent of the patients in the 1.5-mg group, 92 percent of the 3.0-mg group, 78 percent of the 4.5-mg group and 67 percent of the 6.0-mg group. Twenty-five patients withdrew from the study, usually because of adverse reactions such as fatigue, dyspnea, confusion or dizziness. The 6.0-mg dosage group showed a trend toward more adverse reactions, particularly somnolence. At all dosages, the improvement in UPDRS scores between baseline and 10 weeks was statistically significant when compared with placebo. The overall improvement in UPDRS scores was approximately 20 percent over the 10 weeks of treatment.
The authors conclude that pramipexole in dosages of 1.5 mg, 3.0 mg and 4.5 mg per day is safe and effective in improving UPDRS scores in patients with early Parkinson's disease. The long-term effect of pramipexole in forestalling disease progression requires further study.