Effect of Deprenyl on the Progression of Disability in Early Parkinson's Disease

In a clinical trial that is still in progress, we studied the ability of deprenyl and tocopherol, antioxidative agents that act through complementary mechanisms, to delay the onset of disability necessitating levodopa therapy (the primary end point) in patients with early, untreated Parkinson's disease. Eight hundred subjects were randomly assigned in a two-by-two factorial design to receive deprenyl, tocopherol, a combination of both drugs, or placebo, and were followed up to determine the frequency of development of the end point. The interim results of independent monitoring prompted a preliminary comparison of the 401 subjects assigned to tocopherol or placebo with the 399 subjects assigned to deprenyl, alone or with tocopherol. Only 97 subjects who received deprenyl reached the end point during an average 12 months of follow-up, as compared with 176 subjects who did not receive deprenyl (P<10^-8). The risk of reaching the end point was reduced by 57 percent for the subjects who received deprenyl (Cox hazard ratio, 0.43; 95 percent confidence limits, 0.33 and 0.55; P<10^-10). The subjects who received deprenyl also had a significant reduction in their risk of having to give up full-time employment (P = 0.01). We conclude from these preliminary results that the use of deprenyl (10 mg per day) delays the onset of disability associated with early, otherwise untreated cases of Parkinson's disease. (N Engl J Med 1989; 321: 1364–71.) PARKINSON'S disease is a progressively disabling illness that results primarily from the degeneration of dopaminergic neurons in the substantia nigra. The disease symptoms are ameliorated by treatment with levodopa and other dopamine agonists, but the illness progresses, and dopaminergic therapies are often attended by adverse effects on motor function and mental state. Most investigators agree that levodopa therapy should be withheld in patients with early Parkinson's disease until its use is warranted by the severity of functional disability.^{1 2 3} A survey study has indicated that approximately 75 percent of such patients require levodopa therapy within two years of their initial evaluation.