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Loss of long-duration response to levodopa over time in PD

Implications for wearing-off

From the Institute of Neurology (Drs. Zappia, Oliveri, Montesanti, Bosco, Plastino, Aguglia, Gambardella, and Quattrone) and the Faculty of Pharmacy (Dr. Rizzo), University of Catanzaro, Italy; and the Institute of Experimental Medicine and Biotechnology (Drs. Oliveri, Crescibene, Bastone, Gambardella, and Quattrone), National Research Council, Piano Lago di Mangone (Cosenza), Italy.

Address correspondence and reprint requests to Dr. Aldo Quattrone, Clinica Neurologica, Facoltà di Medicina, Via T. Campanella, 88100 Catanzaro, Italy.

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.

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