{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:10:26Z","timestamp":1790838626031,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004718","name":"Universit\u00e9 de Toulouse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004718","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Investigate the efficacy of immediate\u2010release (IR) amantadine in reducing the risk of peak\u2010dose dyskinesia in early Parkinson's disease (PD) as add\u2010on to levodopa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This 22\u2010month, multicenter, randomized, placebo\u2010controlled trial (NCT01538329) enrolled early PD patients on stable levodopa (\u2265150\u2009mg\/day for \u22641\u2009year) without motor complications. The study included three double\u2010blind phases: an 18\u2010month treatment phase with adjunct amantadine\u2010IR (200\u2009mg\/day) or placebo (Period 1), a 3\u2010month delayed\u2010start phase where all participants received amantadine\u2010IR (Period 2), and a 1\u2010month 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\u2010lasting mechanisms of the drug. Exploratory outcomes investigated the potential effects of amantadine\u2010IR on motor and non\u2010motor symptoms and quality of life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 207 patients were randomized to amantadine\u2010IR (N\u2009=\u200999) or placebo (N\u2009=\u2009108). Significantly fewer patients in the amantadine\u2010IR group developed dyskinesia versus placebo during Period 1 (11% vs. 22%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.025), while the mean daily dose of levodopa (95% CI) increased by 70 (21\u2013119)\u2009mg less (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.005). The proportion of patients with dyskinesia was less in the amantadine\u2010IR group versus placebo at the end of Periods 2 and 3, but the difference was not statistically significant (12% vs. 20%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.13 and 16% vs. 22%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.23, 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\u2010IR was in line with previous reports.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Adjunctive amantadine\u2010IR in early PD halved dyskinesia incidence over 18\u2009months. Long\u2010lasting mechanisms could not be demonstrated and merit further investigation. Exploratory positive findings on the potential benefit of amantadine\u2010IR on symptoms like freezing of gait and fatigue also call for further investigation. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70120","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T09:50:48Z","timestamp":1764409848000},"page":"729-740","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effect on Dyskinesia of the Early Combination of Amantadine to Levodopa\u2010Therapy in Parkinson's Disease: A Randomized, Placebo\u2010Controlled Study (\n                    <scp>PREMANDYSK<\/scp>\n                    )"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1410-6397","authenticated-orcid":false,"given":"Olivier","family":"Rascol","sequence":"first","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Clinical Pharmacology and Neurosciences, Parkinson Expert Centre, Clinical Investigation Centre CIC1436 University Hospital of Toulouse, INSERM, University of Toulouse 3  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6179-4500","authenticated-orcid":false,"given":"Fabienne","family":"Ory\u2010Magne","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Clinical Pharmacology and Neurosciences, Parkinson Expert Centre, Clinical Investigation Centre CIC1436 University Hospital of Toulouse, INSERM, University of Toulouse 3  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wassilios G.","family":"Meissner","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurodegenerative Disorders, Parkinson Expert Centre, IMNc, UMR 5293 Bordeaux University Hospital, CNRS, University of Bordeaux  Bordeaux France"},{"name":"Department of Medicine University of Otago, Christchurch, and New Zealand Brain Research Institute  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Malt\u00eate","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology, Parkinson Expert Centre, UMR 1239 Rouen University Hospital, University of Rouen, INSERM  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Defebvre","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology and Movement Disorders, Parkinson Expert Centre, U1172\u2010LilNCog University Hospital of Lille, Lille University  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Philippe","family":"Azulay","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology and Pathology of Movement, Parkinson Expert Centre, UMR7289 AP\u2010HM\u2010Timone Hospital, University of Aix\u2010Marseille, CNRS  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9639-6702","authenticated-orcid":false,"given":"St\u00e9phane","family":"Thobois","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology, Parkinson Expert Centre Lyon Neuroscience Research Centre, PATH\u2010PARK Team U1028, UMR5292  Bron France"},{"name":"Hospital Pierre Wertheimer, Hospices Civils de Lyon University Lyon 1, INSERM, CNRS  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Luc","family":"Houeto","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology, Parkinson Expert Centre, U 1094 EpiMaCT CHU Limoges, INSERM, University of Limoges  Limoges 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Hospital, University of Strasbourg, INSERM, CNRS  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2428-4899","authenticated-orcid":false,"given":"Ana","family":"Marqu\u00e8s","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology, Parkinson Expert Centre, UMR 6602 Clermont\u2010Ferrand University Hospital, CNRS  Clermont\u2010Ferrand France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Viallet","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology, Parkinson Expert Centre Aix\u2010en\u2010Provence Hospital  Aix\u2010en\u2010Provence 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IMNc, UMR 5293 Bordeaux University Hospital, CNRS, University of Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Carri\u00e8re","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology and Movement Disorders, Parkinson Expert Centre, U1172\u2010LilNCog University Hospital of Lille, Lille University  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5947-0432","authenticated-orcid":false,"given":"Eug\u00e9nie","family":"Mutez","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology and Movement Disorders, Parkinson Expert Centre, U1172\u2010LilNCog University Hospital of Lille, Lille University  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise\u2010Laure","family":"Mariani","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology, Parkinson Expert Centre, Clinical Investigation Centre Sorbonne Universit\u00e9, Paris Brain Institute \u2010 ICM, Assistance\u2010Publique H\u00f4pitaux de Paris, INSERM, CNRS  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Eusebio","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology and Pathology of Movement, Parkinson Expert Centre, UMR7289 AP\u2010HM\u2010Timone Hospital, University of Aix\u2010Marseille, CNRS  Marseille 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University of Toulouse 3  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim J.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Lisbon School of Medicine, Faculdade de Medicina Universidade de Lisboa, Lisbon, Portugal and CNS \u2010 Campus Neurol\u00f3gico  Torres Vedras Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Burn","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences Newcastle University, The Medical School  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7325-0199","authenticated-orcid":false,"given":"Jean\u2010Christophe","family":"Corvol","sequence":"additional","affiliation":[{"name":"French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS\u2010PARK)  Toulouse France"},{"name":"Department of Neurology, Parkinson 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