Browse by author
Lookup NU author(s): Professor David BurnORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Objective: Investigate the efficacy of immediate-release (IR) amantadine in reducing the risk of peak-dose dyskinesia in early Parkinson's disease (PD) as add-on to levodopa. Background: While the use of amantadine to manage dyskinesia in PD is well supported by controlled clinical trials, data on its efficacy in patients without motor complications remain limited. Methods: This 22-month, multicenter, randomized, placebo-controlled trial (NCT01538329) enrolled early PD patients on stable levodopa (≥150 mg/day for ≤1 year) without motor complications. The study included three double-blind phases: an 18-month treatment phase with adjunct amantadine-IR (200 mg/day) or placebo (Period 1), a 3-month delayed-start phase where all participants received amantadine-IR (Period 2), and a 1-month washout with placebo (Period 3). The primary outcome was dyskinesia incidence at month 18; secondary outcomes included dyskinesia rates at the end of Periods 2 and 3 to assess potential long-lasting mechanisms of the drug. Exploratory outcomes investigated the potential effects of amantadine-IR on motor and non-motor symptoms and quality of life. Results: A total of 207 patients were randomized to amantadine-IR (N = 99) or placebo (N = 108). Significantly fewer patients in the amantadine-IR group developed dyskinesia versus placebo during Period 1 (11% vs. 22%, P = 0.025), while the mean daily dose of levodopa (95% CI) increased by 70 (21–119) mg less (P = 0.005). The proportion of patients with dyskinesia was less in the amantadine-IR group versus placebo at the end of Periods 2 and 3, but the difference was not statistically significant (12% vs. 20%, P = 0.13 and 16% vs. 22%, P = 0.23, respectively). Mild but significant positive effects on freezing of gait, fatigue, and quality of life were observed during Period 1. The safety profile of amantadine-IR was in line with previous reports. Conclusions: Adjunctive amantadine-IR in early PD halved dyskinesia incidence over 18 months. Long-lasting mechanisms could not be demonstrated and merit further investigation. Exploratory positive findings on the potential benefit of amantadine-IR on symptoms like freezing of gait and fatigue also call for further investigation. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Author(s): Rascol O, Ory-Magne F, Meissner WG, Maltete D, Defebvre L, Azulay J-P, Thobois S, Houeto J-L, Thalamas C, Sommet A, Geny C, Damier P, Anheim M, Marques A, Viallet F, Giroud M, Lefaucheur R, Costentin G, Spampinato U, Mariani L-L, Eusebio A, Prange S, Benatru I, Charif M, Brefel-Courbon C, Fabbri M, Galitzky M, Rousseau V, Ferreira JJ, Burn DJ, Corvol J-C, Rascol O, Ory-Magne F, Thalamas C, Corvol J-C, Defebvre L, Meissner WG, Maltete D, Azulay J-P, Houeto J-L, Thobois S, Viallet F, Samier-Foubert A, Samier-Foubert A, Spampinato U, Boraud T, Tison F, Durif F, Marques A, Debilly B, Bernard S, Giroud M, Carriere N, Carriere N, Mutez E, Mutez E, Torny F, Couratier P, Colin O, Gaudin T, Boutet P, Broussolle E, Prange S, Caire C, Merle H, Eusebio A, Nouira M, Geny C, Charif M, Damier P, Derkinderen P, Faighel M, Talmant V, LeDily S, Mariani L-L, Lacomblez L, Bonnet A-M, Benatru I, Houeto J-L, Ansquer S, Rabois E, Fradet A, Lefaucheur R, Costentin G, Vernon L, Tranchant C, Anheim M, Lagha-Boukbiza O, Wirth T, Sommet A, Rousseau V, Catala H, Catala H, Galiztky M, Saubion A, Saubion A, Brefel-Courbon C, Fabbri M, Ainaoui N, Dellapina E, Salis A, Eyvrard F, Jurado C, Boulloche N, Rey-Zermati J, Boulesteix JJ
Publication type: Article
Publication status: Published
Journal: Movement Disorders
Year: 2025
Pages: epub ahead of print
Online publication date: 29/11/2025
Acceptance date: 27/10/2025
Date deposited: 08/01/2026
ISSN (print): 0885-3185
ISSN (electronic): 1531-8257
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/mds.70120
DOI: 10.1002/mds.70120
Data Access Statement: The data that support the findings of this study are available from the corresponding author (O.R.) upon reasonable request.
PubMed id: 41316871
Altmetrics provided by Altmetric
