Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease

N Engl J Med. 1993 Jan 21;328(3):176-83. doi: 10.1056/NEJM199301213280305.


Background and methods: In 1987 we began a multicenter controlled clinical trial of deprenyl (a monoamine oxidase inhibitor) and tocopherol (a component of vitamin E that traps free radicals) in the treatment of early Parkinson's disease. We randomly assigned 800 patients to one of four treatments: placebo, active tocopherol and deprenyl placebo, active deprenyl and tocopherol placebo, or both active drugs. The primary end point was the onset of disability prompting the clinical decision to begin administering levodopa. An interim analysis showed that deprenyl was beneficial (N Engl J Med 1989;321:1364-71). We report the results of tocopherol treatment after a mean (+/- SD) follow-up of 14 +/- 6 months, as well as the follow-up results for deprenyl.

Results: There was no beneficial effect of tocopherol or any interaction between tocopherol and deprenyl. The beneficial effects of deprenyl, which occurred largely during the first 12 months of treatment, remained strong and significantly delayed the onset of disability requiring levodopa therapy (hazard ratio, 0.50; 95 percent confidence interval, 0.41 to 0.62; P < 0.001). The difference in the estimated median time to the end point was about nine months. The ratings for Parkinson's disease improved during the first three months of deprenyl treatment; the motor performance of deprenyl-treated patients worsened after the treatments were withdrawn.

Conclusions: Deprenyl (10 mg per day) but not tocopherol (2000 IU per day) delays the onset of disability associated with early, otherwise untreated Parkinson's disease. The action of deprenyl that accounts for its beneficial effects remains unclear.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activities of Daily Living
  • Arrhythmias, Cardiac / chemically induced
  • Follow-Up Studies
  • Humans
  • Parkinson Disease / complications
  • Parkinson Disease / drug therapy*
  • Psychiatric Status Rating Scales
  • Psychomotor Performance
  • Regression Analysis
  • Selegiline / administration & dosage
  • Selegiline / adverse effects
  • Selegiline / therapeutic use*
  • Vitamin E / administration & dosage
  • Vitamin E / adverse effects
  • Vitamin E / therapeutic use*


  • Vitamin E
  • Selegiline