Oral Levodopa Formulation Does Not Affect Progression of Parkinson Disease

Abstract

Objective: Motor fluctuations develop in most patients treated with carbidopa/levodopa for Parkinson disease. The continuous dopamine stimulation hypothesis suggests that longer-acting forms of levodopa might improve outcomes, but this has been inadequately tested in humans. We undertook to determine if there is any difference in symptom progression rate among patients taking immediate-release carbidopa/levodopa (IR), controlled-release carbidopa/levodopa (CR), or carbidopa/levodopa/entacapone (CLE) using standard outcome measures in a naturalistic study.

Methods: We evaluated Parkinson disease subjects prospectively followed for up to 48 months in the Parkinson's Disease Biomarker Project. Bayesian linear or generalized linear mixed-effects models were developed to determine if oral levodopa formulation influenced the rate of symptom progression as measured by 8 outcome measures.

Results: At baseline, the IR, CR, and CLE groups were similar except that the CR group had milder disease and was represented at only 1 site, and the CLE group had a longer disease duration. In the primary analysis, there was no difference in rate of symptom progression as measured by the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale Part II, Part IV, or total score. In the secondary exploratory analysis, there was no difference in progression rate as measured by change in levodopa equivalent daily dose, Montreal Cognitive Assessment, Parkinson's Disease Questionnaire mobility subscore, Schwab and England Activities of Daily Living Scale, or a global composite outcome.

Conclusions: We found no difference in symptom progression rate in patients taking IR, CR, or CLE. This clinical observation supports pharmacokinetic studies demonstrating that none of these oral levodopa formulations achieve continuous dopamine stimulation.

Trial registration: ClinicalTrials.gov NCT01767818.

Conflict of interest statement

Conflicts of Interest and Source of Funding: R.B.D. reports personal fees (consulting) from Amneal, Acorda, Supernus, Teva, Adamas, US WorldMeds, Acadia, and Lundbeck, outside the submitted work. For the remaining authors, none were declared. This study was funded by NINDS U01-NS082148 and the Jean Walter Center for Research in Movement Disorders.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Figures

Figure 1.

Change in mean score over 48 months in A. MDS-UPDRS part II score, B. PDQ-39 mobility subscale, and Montreal Cognitive Assessment (MoCA). Error bars represent standard error of the mean. There is no significant difference in symptom progression rate by levodopa formulation.