Loss of long-duration response to levodopa over time in PD: Implications for wearing-off

Objective: To determine the modifications of the long-duration response to levodopa in PD over a 1-year period. Background: The development of predictable motor fluctuations in PD has been attributed mainly to modifications over time of the short-duration response to levodopa, whereas the role of the long-duration response has not been widely investigated. Methods: In 17 patients with PD the authors examined prospectively both the short-duration response and the long-duration response to levodopa under standardized conditions on two different occasions separated by a period of approximately 1 year (11.7 ± 3.6 months). Results: At the end of the follow-up period, the short-duration response increased in magnitude but did not change significantly in duration. A total of 24% of patients lost the long-duration response 1 year after their first examination, but a sustained long-duration response could be reestablished by shortening the interdose interval for levodopa intake. Moreover, the duration of the long-duration response after discontinuation of treatment became significantly shorter during 1 year. Conclusion: Modifications of the long-duration response may have a pivotal role in generating a fluctuating response, and suggest that therapeutic strategies based on maintenance of the long-duration response should be sought to avoid the appearance of motor fluctuations.