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Keywords:

  • washout;
  • long duration response;
  • Parkinson's disease;
  • levodopa–carbidopa;
  • bromocriptine;
  • selegiline;
  • neuroprotection;
  • quantitative model;
  • disease progress

Abstract

In Parkinson's disease, effects of medications on the progression of the underlying disease can be assessed clinically by evaluating patients at baseline prior to treatment and at endpoint following medication washout. With this design, it is critical to employ a washout of sufficient duration to ensure elimination of all symptomatic effects. To assess the time course of resolution of symptomatic effects, we evaluated 31 patients with early Parkinson's disease for 2 weeks following discontinuation of levodopa–carbidopa and bromocriptine after 14 months of treatment. Patients had previously been randomly assigned to treatment with selegiline or placebo, and these had been discontinued 2 months earlier. Data from 20 patients with a clear washout of clinical benefit were used to investigate quantitative models describing the time course of total (Activities of Daily Living + motor) Unified Parkinson's Disease Rating Scale score change. The mean half-life of loss of clinical benefit was 7.9 days (95% confidence interval, 2.2–30.4 days). This indicates that a washout period of 32 days (4 half-lives) may be required to eliminate approximately 90% of the long-term symptomatic effects of levodopa–carbidopa and bromocriptine following their withdrawal from patients with early Parkinson's disease. © 2002 Movement Disorder Society