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Review
. 2025 May;40(5):776-794.
doi: 10.1002/mds.30162. Epub 2025 Mar 8.

Update on Treatments for Parkinson's Disease Motor Fluctuations - An International Parkinson and Movement Disorder Society Evidence-Based Medicine Review

Rob M A de Bie  1 , Regina Katzenschlager  2 , Bart E K S Swinnen  3 , Marina Peball  4 , Shen-Yang Lim  5   6 , Tiago A Mestre  7 , Santiago Perez Lloret  8   9 , Miguel Coelho  10 , Camila Aquino  11 , Ai Huey Tan  5   6 , Veronica Bruno  11 , Joke M Dijk  1 , Beatrice Heim  4 , Chin-Hsien Lin  12 , Linda Azevedo Kauppila  13 , Irene Litvan  14 , René Spijker  15 , Klaus Seppi  4   16 , João Costa  17 , Cristina Sampaio  18   19 , Susan H Fox  20 , Monty A Silverdale  21
Affiliations
Review

Update on Treatments for Parkinson's Disease Motor Fluctuations - An International Parkinson and Movement Disorder Society Evidence-Based Medicine Review

Rob M A de Bie et al. Mov Disord. 2025 May.

Abstract

Objective: To update evidence-based medicine recommendations for treating motor fluctuations of Parkinson's disease (PD).

Background: The International Parkinson and Movement Disorder Society (MDS) Evidence Based Medicine in Movement Disorders Committee recommendations for the treatments of PD were first published in 2002 and regularly updated. The current review uses a new methodology, including the Cochrane Risk of Bias tool and a modified version of GRADE (Grading of Recommendations, Assessment, Development, and Evaluations).

Methods: On January 1, 2023, a literature search was conducted without date limit in the MEDLINE, Embase, and Cochrane databases using the following search terms: Parkinson disease, levodopa and, for the Embase database, randomized controlled trial (RCT). The inclusion criteria for studies were: patients with PD, on oral levodopa therapy, experiencing motor fluctuations, investigating an intervention that was (commercially) available in at least one country, study design RCT, and with a follow-up duration of at least 3 months.

Results: A total of 102 studies were included. Levodopa extended release, pramipexole immediate release and extended release, ropinirole immediate release, rotigotine, opicapone, safinamide, and bilateral subthalamic nucleus deep brain stimulation (DBS) were assessed as efficacious, and continuous intestinal levodopa infusion, continuous subcutaneous levodopa, continuous subcutaneous apomorphine, ropinirole prolonged release, ropinirole patch, entacapone, rasagiline, istradefylline, amantadine extended release, zonisamide, bilateral globus pallidus DBS, and pallidotomy were assessed as likely efficacious for the treatment of motor fluctuations in people with PD who are already being treated with levodopa.

Conclusions: There are several treatment options that can improve motor fluctuations in PD. These recommendations will assist physicians and patients in determining which intervention to use. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; motor response fluctuations; randomized controlled trial; systematic review; treatments.

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Figures

FIG. 1
FIG. 1
Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) search and selection flowchart. *The numbers add up to more than 755 because, for some articles, more than one reason was identified.
See this image and copyright information in PMC

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