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Amantadine use in the French prospective NS-Park cohort

  • Neurology and Preclinical Neurological Studies - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Objective

To assess amantadine use and associated factors in the patients with Parkinson’s disease (PD).

Background

Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat “levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres.

Methods

Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis).

Results

Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12–18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users.

Conclusions

About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs.

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Data availability

Anonymized data from this study will be available from the corresponding author upon reasonable request from any qualified researcher, following the EU General Data Protection Regulation. The study protocol and statistical analysis plan will be shared upon request.

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Acknowledgements

Authors thank the patients for their participation. The authors would also like to thank the coinvestigators of the NSPARK/F-CRIN network study group listed in the “online-only text”. Co-investigators: Amiens: Mickael AUBIGNAT; Besançon: Eloi MAGNIN; Bordeaux: Pr Pierre BURBAUD, Pr Dominique GUEHL, Dr Alexandra FOUBERT-SAMIER, Dr Brice LAURENS, Dr Thomas BORAUD, Dr Sylvain VERGNET, Dr David BENDETOWICZ; Caen: Thomas PALPACUER; Clermont-Ferrand: Bérengère DEBILLY, Philippe DEROST, Charlotte BEAL; Créteil—Henri Mondor: Hayet SALHI, Alice DORMEUIL, Aimée PETIT, Alban GRAVIER; Dijon: Gwendoline DUPONT, Lucie GARNIER; Grenoble : Valérie FRAIX, Anna CASTRIOTO, Sara MEONI; Lille: Nicolas CARRIERE; Lyon: Teodor DANAILA, Chloé LAURENCIN, Stéphane THOBOIS; Marseille: Jean-Philippe AZULAY, Frédérique FLUCHERE; Montpellier: Mahmoud CHARIF, Marie-Christine PICOT; Nancy: Lucie HOPES; Nantes: Anne-Gaelle CORBILLE, Tiphaine ROUAUD, Pascal DERKINDEREN; Nice: Cosmin ALECU, Charlotte HERAUD; Nîmes: Marie DE VERDAL; Paris—Pitié- Salpêtrière: Bertrand DEGOS, Graziella MANGONE, Sara SAMBIN, Aymeric LANORE, Thomas COURTIN, Louise-Laure MARIANI, David BENDETOWICZ, Fouad KHOURY, Poornima MENON, Florence CORMIER-DEQUAIRE, Emmanuel FLAMAND-ROZE, David GRABLI, Elodie HAINQUE, Marie VIDHAILLET, Aurélie MENERET, Cécile DELORME, Cendrine FOUCARD, Florian VON RAISON, Alexis ELBAZ, Andreas HARTMANN, Vincent LECLERCQ; Poitiers: Solène ANSQUER; Rennes: Frederique LEH, Marion LECLERCQ; Rouen: Guillaume COSTENTIN; Strasbourg: Ouhaid LAGHA BOUKBIZA; Toulouse: Fabienne ORY-MAGNE, Christine BREFEL COURBON, Clemence LEUNG, Hélène CATALA. Data collection contributors (Project Managers, Clinical Research Associate, Study Nurses, Secretary, Neuropsychologist): Amiens: Astrid CAUSEL; Besançon: Emilie Gaiffe; Bordeaux: Sandrine DUPOUY, Sandrine VILLARS, Wei-Ho LAI ; Caen: Rachida BARI, Damien CHEVANNE; Clermont-Ferrand: Elodie DURAND, Isabelle RIEU, Stephane BERNARD, Corinne GARSAULT; Créteil—Henri Mondor: Noel BOUDJEMA ; Dijon: Pascale GREBENT; Grenoble: Andrea KISTNER, Pierre PELISSIER; Lille: Valérie SANTRAINE; Limoges: Thomas GAUDIN, Pierre BOUTET; Lyon: Catherine CAIRE; Marseille: Manel NOUIRA; Montpellier : Claudia VERNA; Nancy: Amory JARDEL, Salomé PUISIEUX, Guillemette CLEMENT, Lili LE MONNIER; Nantes: Régis FRENAIS, Séverine LE DILY, Rachel CHAIGNEAU; Nice: Vanessa FERRIER, Elodie DAVID; Nîmes: Leslie FRA, Elsa FOUCARAN; Paris—Pitié- Salpêtrière: Carole DONGMO-KENFACK, Florence BEAUZOR, Mickael LE, Sonia MESSAR, Sophie LIOT; Poitiers: Emilie RABOIS; Reims: Margaux BONNAIRE-VERDIER; Rennes: Françoise KESTENS, Rozenn GOURHAN, Sandra LOPEZ-ALFARO, Jean-François HOUVENAGHEL, Mélanie ALEXANDRE, Christine BOURDONNAIS; Rouen: Linda VERNON, Ahmed BOUMEDIENE; Strasbourg: Céline Julie, Aurette Lobstein, Nadine Longato, Marie-Pierre Mitterle, Clélie Philips, Hugo Rummel ; Toulouse: Stéphanie BRAS, Estelle HARROCH, Claudia GILLET.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology and Neurosciences, Clinical Investigation Center CIC1436, Toulouse Parkinson Expert Centre, Toulouse NeuroToul Center of Excellence in Neurodegeneration (COEN), University of Toulouse 3, CHU of Toulouse, INSERM, Toulouse, France

    Margherita Fabbri & Olivier Rascol

  2. Service de Pharmacologie Médicale et Clinique, Centre Hospitalier Universitaire-Faculté de Médecine, Toulouse, France

    Margherita Fabbri, Samuel Tessier & Olivier Rascol

  3. French NS-PARK/F-CRIN Network, Clermont-Ferrand, France

    Margherita Fabbri, Jean-Christophe Corvol, Yajiththa Selvarasa, Stephanie Carvalho, Véronique Chaigneau, Christine Brefel-Courbon, Fabienne Ory-Magne, Melissa Tir, Matthieu Bereau, Wassilios G. Meissner, Claire Thiriez, Ana Marques, Philippe Remy, Vincent Schneider, Elena Moro, Luc Defebvre, Jean Luc Houeto, Stephane Prange, Alexandre Eusebio, Christian Geny, Solène Frismand, Philippe Damier, Caroline Giordana Reuther, Giovanni Castelnovo, Isabelle Benatru, Anne Doe De Maindreville, Sophie Drapier, David Maltête, Ouhaid Lagha-Boukbiza & Olivier Rascol

  4. Department of Clinical Pharmacology, Clinical Investigation Center CIC1436, Centre Hospitalier Universitaire de Toulouse, Toulouse, France

    Vanessa Rousseau & Agnès Sommet

  5. Sorbonne Université, Institut du Cerveau, Paris Brain Institute, ICM, Inserm, CNRS, Paris, France

    Jean-Christophe Corvol, Yajiththa Selvarasa & Stephanie Carvalho

  6. Department of Neurology, Assistance Publique Hôpitaux de Paris, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France

    Jean-Christophe Corvol, Yajiththa Selvarasa & Stephanie Carvalho

  7. Sorbonne Université, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), Unité de Recherche Clinique PSL-CFX, CIC-1901, F75013, Paris, France

    Florence Tubach, Yann De Rycke & Nathalie Bertille

  8. Department of Clinical Pharmacology and Neurosciences, Parkinson Expert Center, Clinical Investigation Center CIC1436, University Hospital of Toulouse, NeuroToul COEN (Center of Excellence in Neurodegeneration), Toulouse NeuroImaging Center, Inserm, University of Toulouse 3, Toulouse, France

    Christine Brefel-Courbon

  9. Service de Neurologie, Centre Hospitalier Universitaire, Toulouse, Université de Toulouse-Toulouse 3, INSERM, UMR1214 Toulouse NeuroImaging Centre “TONIC,” Center of Excellence in Neurodegeneration (CoEN), NeuroToul, Parkinson Expert Center, Clinical Investigation Center CIC1436, Toulouse, France

    Fabienne Ory-Magne

  10. Department of Neurology, University Hospital of Amiens, Amiens, France

    Melissa Tir

  11. Department of Neurology, University Hospital of Besançon, Besançon, France

    Matthieu Bereau

  12. CHU Bordeaux, Service de Neurologie des Maladies Neurodégénératives, IMNc, NS-Park/FCRIN Network, 33000, Bordeaux, France

    Wassilios G. Meissner

  13. Univ. Bordeaux, CNRS, IMN, UMR5293, 33000, Bordeaux, France

    Wassilios G. Meissner

  14. Dept. Medicine, University of Otago, Christchurch, New Zealand

    Wassilios G. Meissner

  15. New Zealand Brain Research, Christchurch, New Zealand

    Wassilios G. Meissner

  16. Department of Neurology and Parkinson Expert Centre, Caen University-Hospital, Caen, France

    Claire Thiriez

  17. Neurology Department, Université Clermont Auvergne, EA7280 NPsy-Sydo, Clermont-Ferrand University Hospital, Clermont-Ferrand, France

    Ana Marques

  18. Centre Expert Parkinson, Neurologie, CHU Henri Mondor, AP-HP, Equipe NPI, IMRB INSERM Et Faculté de Santé, Université Paris-Est Créteil, Créteil, France

    Philippe Remy

  19. Département de Neurologie, Centre Hospitalier Universitaire François Mitterrand, Université de Bourgogne, Dijon, France

    Vincent Schneider

  20. Unité des Troubles du Movement, Service de Neurologie, Coordinatrice du Pole PRENELE, CHU de Grenoble, Assesseur Relations Internationales, Faculté de Médécine, Université Grenoble Alpes, President Elect, European Academy of Neurology, Grenoble, France

    Elena Moro

  21. Movement Disorders Department, Lille University, Inserm 1172, Lille, France

    Luc Defebvre

  22. Department of Neurology, Limoges University Hospital, Inserm, U1094, EpiMaCT-Epidemiology of Chronic Diseases in Tropical Zone, 87042, Limoges Cedex 01, France

    Jean Luc Houeto

  23. Hospices Civils de Lyon, Pierre Wertheimer Neurological Hospital, Expert Parkinson Center, Lyon University, Bron, France

    Stephane Prange

  24. Université Claude Bernard Lyon 1, Faculté de Médecine et de Maïeutique Lyon Sud Charles Mérieux, Oullins, France

    Stephane Prange

  25. Marc Jeannerod Institute for Cognitive Neuroscience, CNRS, UMR 5229, Bron, France

    Stephane Prange

  26. Movement Disorders Unit, Neurology Department, University Hospital of Marseille, Marseille, France

    Alexandre Eusebio

  27. EuroMov, Univ. Montpellier, Montpellier, France

    Christian Geny

  28. Department of Neurology, CHRU Montpellier, Montpellier, France

    Christian Geny

  29. Service de Neurologie, Centre Expert Parkinson, Centre Mémoire de Ressources et de Recherche de Lorraine, Hôpital Central Nancy, Nancy, France

    Solène Frismand

  30. Service de Neurologie, CHU Nantes, INSERM, CIC, 1413, Nantes, France

    Philippe Damier

  31. Department of Neurology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France

    Caroline Giordana Reuther

  32. Department of Neurology, University Hospital of Nîmes, Nîmes, France

    Giovanni Castelnovo

  33. Departement of Neurology, Poitiers University Hospital, INSERM, CHU de Poitiers, Centre d’Investigation Clinique CIC1402, Poitiers, France

    Isabelle Benatru

  34. Department of Neurology, Hôpital Maison Blanche, Reims, France

    Anne Doe De Maindreville

  35. Department of Neurology, Pontchaillou University Hospital, CIC INSERM 1414, Rennes, France

    Sophie Drapier

  36. Department of Neurology, Rouen University Hospital and University of Rouen, Rouen, France

    David Maltête

  37. Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, CEP Rouen, INSERM U1239, Mont-Saint-Aignan, France

    David Maltête

  38. Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    Ouhaid Lagha-Boukbiza

Authors
  1. Margherita Fabbri
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  2. Vanessa Rousseau
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  3. Jean-Christophe Corvol
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  4. Agnès Sommet
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  5. Florence Tubach
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  6. Yann De Rycke
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  7. Nathalie Bertille
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  8. Yajiththa Selvarasa
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  9. Stephanie Carvalho
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  10. Véronique Chaigneau
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  11. Christine Brefel-Courbon
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  12. Fabienne Ory-Magne
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  13. Samuel Tessier
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  14. Melissa Tir
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  15. Matthieu Bereau
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  16. Wassilios G. Meissner
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  17. Claire Thiriez
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  18. Ana Marques
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  19. Philippe Remy
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  20. Vincent Schneider
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  21. Elena Moro
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  22. Luc Defebvre
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  23. Jean Luc Houeto
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  24. Stephane Prange
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  25. Alexandre Eusebio
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  26. Christian Geny
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  27. Solène Frismand
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  28. Philippe Damier
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  29. Caroline Giordana Reuther
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  30. Giovanni Castelnovo
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  31. Isabelle Benatru
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  32. Anne Doe De Maindreville
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  33. Sophie Drapier
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  34. David Maltête
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  35. Ouhaid Lagha-Boukbiza
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  36. Olivier Rascol
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Consortia

for the French N. S.-Park network

  • Mickael Aubignat
  • , Eloi Magnin
  • , Pr Pierre Burbaud
  • , Pr Dominique Guehl
  • , Alexandra Foubert-Samier
  • , Brice Laurens
  • , Thomas Boraud
  • , Sylvain Vergnet
  • , David Bendetowicz
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Corresponding author

Correspondence to Margherita Fabbri.

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Conflict of interest

Isabelle Benatru, Giovani Castelnovo, Anne-Gaelle Corbille, Jean-Christophe Corvol, Anne Doe de Maindreville, Sophie Drapier, Alexandre Eusabio, Solène Frismand, Christian Gény, Caroline Giordana Reuther, Jean-Luc Houeto, David Maltête, Ana Marques, Wassilios Meissner, Stephane Prange Philippe Rémy, Vanessa Rousseau, Vincent Schneider, Melissa Tir and Ouhaid Lagha-Boukbiza report no disclosures. Margherita Fabbri received Honoraria to speak from AbbVie, ORKYN, and BIAL, consultancies from BIAL and LVL Medical; Grant from France Parkinson, HORIZON 2022 and MSA Coalition. Matthieu Bereau reports grants from France Parkinson Foundation, reimbursement of travel expenses to scientific meetings from Asten, Boston Scientific, Elivie and Medtronic, honoraria from AbbVie, Aguettan, Allergan, Asdia and Merz Pharma for lecturing outside the submitted work. Christine Brefel-Courbon has received research grant from Association France Parkinson, and fees for lectures and consultancies from Aguettant, Orkyn, NHC, Zambon and AbbVie. Luc Defebvre served on the Scientific Advisory Board for Abbvie and has received honoraria from pharmaceutical companies for consultancy and lectures including Abbvie, Novartis, Aguettant, Orkyn. E Moro has received honoraria from Medtronic for consulting services. She has also received research grant support from Abbott, France Parkinson, and Ipsen. Fabienne Ory-Magne has received honoraria for serving as an advisory board member from Abbvie, Medtronic, Orphalan, Aguettant and Orkyn, and for consultancy activities from Aguettant, Abbvie, Orphalan, Ellivie, Homeperf and Orkyn. Olivier Rascol has acted as a scientific advisor for drug companies developing antiparkinsonian medications (Abbott, Abbvie, Acorda, Adamas, BIAL, Biogen, Boehringer-Ingelheim, Cynapsus, GSK, Impax, Merck, Osmotica, Oxford-Biomedica, Lundbeck, Novartis, Prexton, Servier, Sunovion, TEVA, UCB, Zambon). Claire Thiriez reports no financial disclosure; congress travel grant from Orkyn, Abbvie, homeperf, ADELIA, ASDIA, Ipsen. Philippe Damier has received honoraria from Teva, Kyowa Kirin for consulting services and from Abbvie, Roche, Novartis, Teva for conferences.

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Fabbri, M., Rousseau, V., Corvol, JC. et al. Amantadine use in the French prospective NS-Park cohort. J Neural Transm (2024). https://doi.org/10.1007/s00702-024-02772-4

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