Does Late Levodopa Administration Delay the Development of Dyskinesia in Patients with De Novo Parkinson’s Disease?



It remains controversial whether late levodopa administration is a reasonable approach to reducing the risk of levodopa-induced dyskinesia in Parkinson’s disease.


This study aimed to investigate the effects of levodopa sparing on the development of levodopa-induced dyskinesia.


We retrospectively reviewed medical records for patients with de novo Parkinson’s disease who visited the Yonsei Parkinson Center between April 2009 and June 2015 and received at least 2 years of treatment. Among 657 patients with drug-naïve Parkinson’s disease who met the study criteria, 90 were initially treated with dopamine agonists (levodopa-sparing group; levodopa supplementation after 2.15 years). Another 90 patients who were initially treated with levodopa (levodopa group) were matched to the 90 patients for age, sex, follow-up duration, Parkinson’s disease duration, Unified Parkinson’s Disease Rating Scale Part III scores, and baseline dopamine transporter availability in the posterior putamen. The effects of levodopa sparing on dyskinesia development were assessed with Kaplan–Meier estimates and a stratified Cox regression model adjusted for age of onset, sex, dopamine transporter availability, and daily levodopa dose per weight.


The levodopa-sparing group had a comparable age of onset (54.80 ± 7.36 years) to the levodopa group (56.53 ± 6.16 years). The Kaplan–Meier analysis revealed that the risk of levodopa-induced dyskinesia after treatment initiation was similar between the groups. Once the levodopa-sparing group started levodopa supplementation, they had a higher risk of developing levodopa-induced dyskinesia. However, a stratified Cox regression model indicated that hazard ratios for levodopa sparing to levodopa-induced dyskinesia development were 0.138 (95% confidence interval 0.024–0.785) after treatment initiation and 0.438 (95% confidence interval 0.105–1.832) after levodopa initiation.


Late levodopa administration was associated with a low risk of dyskinesia after adjusting for confounding effects and may be a reasonable strategy for prolonging the levodopa-induced dyskinesia-free period in Parkinson’s disease.

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Corresponding author

Correspondence to Phil Hyu Lee.

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This research was supported by a Grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Republic of Korea (Grant No. HI16C1118), and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (Grant No. NRF-2018R1D1A1B07048959).

Conflict of interest

Seok Jong Chung, Han Soo Yoo, Hye Sun Lee, Hyo Eun Jeong, Soo-Jong Kim, Jungsu S. Oh, Jae Seung Kim, Young H. Sohn, and Phil Hyu Lee have no conflicts of interest directly relevant to the content of this article.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Chung, S.J., Yoo, H.S., Lee, H.S. et al. Does Late Levodopa Administration Delay the Development of Dyskinesia in Patients with De Novo Parkinson’s Disease?. CNS Drugs 32, 971–979 (2018).

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