Financial Support: Dr. Rajput has received unrestricted research grants from Royal University Hospital Foundation, Greystone Golf Classic, and Regina Curling Classic.
Letters: Published Article
Factors predictive of the development of levodopa-induced dyskinesia and Wearing-Off in Parkinson's disease
Article first published online: 27 DEC 2013
© 2013 The Author. International Parkinson and Movement Disorder Society published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Volume 29, Issue 3, page 429, March 2014
How to Cite
Rajput, A. H. (2014), Factors predictive of the development of levodopa-induced dyskinesia and Wearing-Off in Parkinson's disease. Mov. Disord., 29: 429. doi: 10.1002/mds.25800
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 17 MAR 2014
- Article first published online: 27 DEC 2013
- Manuscript Accepted: 8 DEC 2013
- Manuscript Revised: 10 OCT 2013
- Manuscript Received: 24 SEP 2013
I read the interesting report by Olanow et al. regarding factors predictive of the development of levodopa (l-dopa)-induced dyskinesia and wearing-off in Parkinson's disease. l-Dopa has been widely used for more than 40 years, but a dose-finding study was never performed. I congratulate the authors for addressing this very important issue of l-dopa dosing. Their study provides scientific rationale for using as low a dose of l-dopa as clinically necessary for symptomatic control of Parkinson's disease while reducing dyskinesias and motor response fluctuations.
Although intravenous l-dopa was reported as effective in 1961, oral therapy with this drug became possible only after a 1967 report by Cotzias et al. based on a study of 17 patients. They used dihydroxyphenylalanine, DL-3,4-(alanine-1-14C) (D-l-dopa), “…because of the great expense of the l-compound.” The dose of D-l-dopa in most of their patients was 9 g or higher and was up to 16 g in some patients. Soon, l-dopa became commercially available, but there was no clinical trial to establish the optimal dose. Neurologists used the l-dopa dose with which they felt comfortable.
Dyskinesia was the first motor complication of l-dopa observed by most experts. On 6 g of l-dopa daily (equivalent to 1200 mg carbidopa–l-dopa [Sinemet; Merck & Company, Inc., Whitehouse Station, NJ]), 58% of patients had dyskinesias by the end of 6 months, and 75% had dyskinesias by the end of 1 year.
We received authorization for l-dopa use as the second wave of neurologists in this field. As such, we had access to some of the observations made by others, and we witnessed severe dyskinesia in some patients on high l-dopa doses. The benefit/adverse effects profile did not seem to be favorable for l-dopa therapy. Therefore, we decided to use a lower dose and slower titration of l-dopa, targeting a dose of 3 g (Sinemet 600 mg) or lower. We reported our 12-year observations on low-dose l-dopa therapy in 1984.5 The incidence of dyskinesia was markedly lower than reported by others. By the end of 1 year, only 15% of our patients had dyskinesia, and only 3% had wearing-off or wearing-on/wearing-off. We have continued to use a low dose of l-dopa. The incidence of both dyskinesias and motor response fluctuations in our longitudinally followed autopsy cases of Parkinson's disease was much lower compared with the incidence reported in most of the literature. It is encouraging to see that an l-dopa dosing regimen similar to that started empirically in the late 1960s now has more robust data to support it.
Ali H. Rajput, MBBS, FRCPC
University of Saskatchewan/Saskatoon Health Region, Saskatoon, Saskatchewan, Canada
- 1Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) Investigators. Factors predictive of the development of levodopa-induced dyskinesia and wearing-off in Parkinson's disease. Mov Disord 2013;28:1064-1071., , , et al;
- 4Clinical aspects of abnormal movements induced by L-dopa. In: Barbeau A, McDowell FH, editors. L-Dopa and Parkinsonism. Philadelphia, PA: F.A. Davis Company; 1970:101-108..