This article is a US Government work and, as such, is in the public domain in the United States of America.
Evolution of the response to levodopa during the first 4 years of therapy†
Article first published online: 21 MAY 2002
Published Wiley-Liss, Inc.
Annals of Neurology
Volume 51, Issue 6, pages 686–693, June 2002
How to Cite
Nutt, J. G., Carter, J. H., Lea, E. S. and Sexton, G. J. (2002), Evolution of the response to levodopa during the first 4 years of therapy. Ann Neurol., 51: 686–693. doi: 10.1002/ana.10189
- Issue published online: 21 MAY 2002
- Article first published online: 21 MAY 2002
- Manuscript Revised: 22 JAN 2002
- Manuscript Accepted: 22 JAN 2002
- Manuscript Received: 5 OCT 2001
- Veterans Administration Parkinson's Disease Research, Education and Clinical Center (PADRECC, J.G.N.)
- National Parkinson Foundation (J.G.N.)
- National Institutes of Health. Grant Number: NIH-NINDS RO1-NS21062 (J.G.N.)
- General Clinical Research Center. Grant Number: RR000334
The short-duration response, long-duration response, and dyskinetic response to levodopa change during long-term levodopa therapy. How these responses evolve, and which changes contribute to the emergence of motor fluctuations, remain unclear. We studied 18 subjects with Parkinson's disease before they began levodopa therapy and after 6, 12, 24, and 48 months of long-term levodopa therapy. The responses to 2-hour levodopa infusions after overnight and after 3 days of levodopa withdrawal were studied from 6 months onward. The mean magnitude of the short-duration response and the long-duration response measured after overnight without antiparkinsonian medications did not change during the 4 years. However, after 3 days without levodopa, it was apparent that the short-duration-response magnitude was progressively increasing (p < 0.0001) and that the long-duration response was decaying more rapidly (p = 0.0004). The short-duration-response magnitude at 4 years was inversely related to the long-duration-response magnitude (p = 0.022), suggesting that the long-duration response was one determinant of the short-duration-response magnitude. Dyskinesia increased progressively in severity during the study (p = 0.013). The duration of the short-duration response and dyskinesia did not change during the 4 years. Subject reports of motor fluctuations tended to be associated with a large short-duration response (p = 0.054). We suggest that a larger long-duration response, rather than a shortened one, is more important to the development of fluctuations. Improving the baseline or practical-off motor function to reduce the magnitude of the short-duration response may be a strategy to treat fluctuations.