Inferring the long duration response to levodopa in Parkinson's disease

Introduction: The long duration response to levodopa in Parkinson's disease outlasts drug elimination by days to weeks. Though a substantive part of anti-parkinsonian motor benefit, it cannot easily be observed. Objectives: To infer the magnitude of the long duration response during the first decade of Parkinson's disease and identify factors that influence it. Methods: Serial practically defined off scores of 24 patients from a longitudinal study of levodopa short duration response were used to establish their rate of motor progression. A line of notional untreated disability (as if drug treatment had never been given) with the same progression gradient was the basis for calculation of the long duration response. Predictors of mean long duration response amplitude were identified using a multiple linear regression model. Results: Over a mean treatment period of 16.6 +/- 4.4 years, annual increase in motor disability was 2.3% of the maximum score. The long duration response composed 49% of total levodopa response during the first decade of treatment, and this proportion was significantly higher soon after commencing levodopa (p = 0.001). Higher pre-treatment motor score (r = 0.60) and lower MMSE (r = 0.60) were the main predictors of a larger long duration response. There was little correlation between long and short duration responses. Conclusions: Long duration responses contribute almost half of the total levodopa benefit during the first decade of treatment. An appreciation of both long and short duration components of drug symptomatic effects is important in clinical trial design to investigate possible neuroprotective treatments.