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

Background It remains controversial whether late levodopa administration is a reasonable approach to reducing the risk of levodopa-induced dyskinesia in Parkinson's disease. Objective This study aimed to investigate the effects of levodopa sparing on the development of levodopa-induced dyskinesia. Methods 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-naive 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. Results 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. Conclusion 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.