Effect on Dyskinesia of the Early Combination of Amantadine to Levodopa‐Therapy in Parkinson's Disease: A Randomized, Placebo‐Controlled Study ( PREMANDYSK )
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: 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.
Source: Movement Disorders
DOI: 10.1002/mds.70120
Authors: Olivier Rascol, Fabienne Ory‐Magne, Wassilios G. Meissner, David Maltête, Luc Defebvre, Jean‐Philippe Azulay, Stéphane Thobois, Jean‐Luc Houeto, Claire Thalamas, Agnès Sommet, Christian Geny, Philippe Damier, Mathieu Anheim, Ana Marquès, François Viallet, Maurice Giroud, Romain Lefaucheur, Guillaume Costentin, Umberto Spampinato, Alexandra Samier‐Foubert, Nicolas Carrière, Eugénie Mutez, Louise‐Laure Mariani, Alexandre Eusebio, Stéphane Prange, Isabelle Benatru, Mahmoud Charif, Christine Brefel‐Courbon, Margherita Fabbri, Monique Galitzky, Vanessa Rousseau, Amandine Saubion, Hélène Catala, Joaquim J. Ferreira, David J. Burn, Jean‐Christophe Corvol, the PREMANDYSK Study Group
Institutions: Université Toulouse III - Paul Sabatier, Inserm, Centre Hospitalier Universitaire de Toulouse, Centre d’Investigation Clinique 1436, Université de Toulouse, Centre National de la Recherche Scientifique, Université de Bordeaux, Centre Hospitalier Universitaire de Bordeaux, Institut des Maladies Neurodégénératives, New Zealand Brain Research Institute, University of Otago, Université de Rouen Normandie, Université de Lille, Centre Hospitalier Universitaire de Lille, Lille Neurosciences & Cognition, Aix-Marseille Université, Assistance Publique Hôpitaux de Marseille, Institut de Neurosciences de la Timone, Hôpital de la Timone, Centre de Recherche en Neurosciences de Lyon, Hospices Civils de Lyon, Hôpital Pierre Wertheimer, Centre Hospitalier Universitaire de Limoges, Université de Limoges, Centre Hospitalier Universitaire de Montpellier, Centre Hospitalier Universitaire de Nantes, Centre d'Investigation Clinique de Nantes, Nantes Université, Institut de génétique et de biologie moléculaire et cellulaire, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Institut Pascal, Centre Hospitalier Universitaire de Clermont-Ferrand, CHU Dijon Bourgogne, Centre Hospitalier Universitaire de Rouen, Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Institut du Cerveau, Université de Poitiers, Centre Hospitalier Universitaire de Poitiers, University of Lisbon, Newcastle University
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,480
OpenAlex ID: W4416813693