Amantadine use in the French prospective NS-Park cohort

Margherita Fabbri, Vanessa Rousseau, Jean-Christophe Corvol, Agnès Sommet, Florence Tubach, Yann De Rycke, Nathalie Bertille, Yajiththa Selvarasa, Stephanie Carvalho, Véronique Chaigneau, Christine Brefel-Courbon, Fabienne Ory-Magne, Samuel Tessier, 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, Mickael Aubignat, Eloi Magnin, Pr Pierre Burbaud, Pr Dominique Guehl, Alexandra Foubert-Samier, Brice Laurens, Thomas Boraud, Sylvain Vergnet, David Bendetowicz, Thomas Palpacuer, Bérengère Debilly, Philippe Derost, Charlotte Beal, Hayet Salhi, Alice Dormeuil, Aimée Petit, Alban Gravier, Gwendoline Dupont, Lucie Garnier, Valérie Fraix, Anna Castrioto, Sara Meoni, Nicolas Carriere, Teodor Danaila, Chloé Laurencin, Stéphane Thobois, Jean-Philippe Azulay, Frédérique Fluchere, Mahmoud Charif, Marie-Christine Picot, Lucie Hopes, Anne-Gaelle Corbille, Tiphaine Rouaud, Pascal Derkinderen, Cosmin Alecu, Charlotte Heraud, Marie De Verdal, Bertrand Degos, Graziella Mangone, Sara Sambin, Aymeric Lanore, Thomas Courtin, Louise-Laure Mariani, 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, Solène Ansquer, Frederique Leh, Marion Leclercq, Guillaume Costentin, Lagha Boukbiza, Christine Brefel Courbon, Clemence Leung, Hélène Catala, Astrid Causel, Emilie Gaiffe, Sandrine Dupouy, Sandrine Villars, Wei-Ho Lai, Rachida Bari, Damien Chevanne, Elodie Durand, Isabelle Rieu, Stephane Bernard, Corinne Garsault, Noel Boudjema, Pascale Grebent, Andrea Kistner, Pierre Pelissier, Valérie Santraine, Thomas Gaudin, Pierre Boutet, Catherine Caire, Manel Nouira, Claudia Verna, Amory Jardel, Salomé Puisieux, Guillemette Clement, Lili Le Monnier, Régis Frenais, Séverine Le Dily, Rachel Chaigneau, Vanessa Ferrier, Elodie David, Leslie Fra, Elsa Foucaran, Carole Dongmo-Kenfack, Florence Beauzor, Mickael Le, Sonia Messar, Sophie Liot, Emilie Rabois, Margaux Bonnaire-Verdier, Françoise Kestens, Rozenn Gourhan, Sandra Lopez-Alfaro, Jean-François Houvenaghel, Mélanie Alexandre, Christine Bourdonnais, Linda Vernon, Ahmed Boumediene, Céline Julie, Aurette Lobstein, Nadine Longato, Marie-Pierre Mitterle, Clélie Philips, Hugo Rummel, Stéphanie Bras, Estelle Harroch, Claudia Gillet,
J Neural Transm. 2024-04-05; :
DOI: 10.1007/s00702-024-02772-4


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Fabbri M(1)(2)(3), Rousseau V(4), Corvol JC(5)(6)(7), Sommet A(4), Tubach F(8),
De Rycke Y(8), Bertille N(8), Selvarasa Y(5)(6)(7), Carvalho S(5)(6)(7),
Chaigneau V(5), Brefel-Courbon C(5)(9), Ory-Magne F(5)(10), Tessier S(11), Tir
M(5)(12), Bereau M(5)(13), Meissner WG(5)(14)(15)(16)(17), Thiriez C(5)(18),
Marques A(5)(19), Remy P(5)(20), Schneider V(5)(21), Moro E(5)(22), Defebvre
L(5)(23), Houeto JL(5)(24), Prange S(5)(25)(26)(27), Eusebio A(5)(28), Geny
C(5)(29)(30), Frismand S(5)(31), Damier P(5)(32), Reuther CG(5)(33), Castelnovo
G(5)(34), Benatru I(5)(35), De Maindreville AD(5)(36), Drapier S(5)(37), Maltête
D(5)(38)(39), Lagha-Boukbiza O(5)(40), Rascol O(41)(11)(5); French N. S.-Park
network.

Collaborators: Aubignat M, Magnin E, Burbaud PP, Guehl PD, Foubert-Samier A,
Laurens B, Boraud T, Vergnet S, Bendetowicz D, Palpacuer T, Debilly B, Derost P,
Beal C, Salhi H, Dormeuil A, Petit A, Gravier A, Dupont G, Garnier L, Fraix V,
Castrioto A, Meoni S, Carriere N, Danaila T, Laurencin C, Thobois S, Azulay JP,
Fluchere F, Charif M, Picot MC, Hopes L, Corbille AG, Rouaud T, Derkinderen P,
Alecu C, Heraud C, De Verdal M, Degos B, Mangone G, Sambin S, Lanore A, Courtin
T, Mariani LL, Bendetowicz D, Khoury F, Menon P, Cormier-Dequaire F,
Flamand-Roze E, Grabli D, Hainque E, Vidhaillet M, Meneret A, Delorme C, Foucard
C, Von Raison F, Elbaz A, Hartmann A, Leclercq V, Ansquer S, Leh F, Leclercq M,
Costentin G, Lagha Boukbiza, Brefel Courbon C, Leung C, Catala H, Causel A,
Gaiffe E, Dupouy S, Villars S, Lai WH, Bari R, Chevanne D, Durand E, Rieu I,
Bernard S, Garsault C, Boudjema N, Grebent P, Kistner A, Pelissier P, Santraine
V, Gaudin T, Boutet P, Caire C, Nouira M, Verna C, Jardel A, Puisieux S, Clement
G, Le Monnier L, Frenais R, Le Dily S, Chaigneau R, Ferrier V, David E, Fra L,
Foucaran E, Dongmo-Kenfack C, Beauzor F, Le M, Messar S, Liot S, Rabois E,
Bonnaire-Verdier M, Kestens F, Gourhan R, Lopez-Alfaro S, Houvenaghel JF,
Alexandre M, Bourdonnais C, Vernon L, Boumediene A, Julie C, Lobstein A, Longato
N, Mitterle MP, Philips C, Rummel H, Bras S, Harroch E, Gillet C.

Author information:
(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. .
(2)Service de Pharmacologie Médicale et Clinique, Centre Hospitalier
Universitaire-Faculté de Médecine, Toulouse, France.
.
(3)French NS-PARK/F-CRIN Network, Clermont-Ferrand, France.
.
(4)Department of Clinical Pharmacology, Clinical Investigation Center CIC1436,
Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
(5)French NS-PARK/F-CRIN Network, Clermont-Ferrand, France.
(6)Sorbonne Université, Institut du Cerveau, Paris Brain Institute, ICM, Inserm,
CNRS, Paris, France.
(7)Department of Neurology, Assistance Publique Hôpitaux de Paris, CIC
Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France.
(8)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.
(9)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.
(10)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.
(11)Service de Pharmacologie Médicale et Clinique, Centre Hospitalier
Universitaire-Faculté de Médecine, Toulouse, France.
(12)Department of Neurology, University Hospital of Amiens, Amiens, France.
(13)Department of Neurology, University Hospital of Besançon, Besançon, France.
(14)CHU Bordeaux, Service de Neurologie des Maladies Neurodégénératives, IMNc,
NS-Park/FCRIN Network, 33000, Bordeaux, France.
(15)Univ. Bordeaux, CNRS, IMN, UMR5293, 33000, Bordeaux, France.
(16)Dept. Medicine, University of Otago, Christchurch, New Zealand.
(17)New Zealand Brain Research, Christchurch, New Zealand.
(18)Department of Neurology and Parkinson Expert Centre, Caen
University-Hospital, Caen, France.
(19)Neurology Department, Université Clermont Auvergne, EA7280 NPsy-Sydo,
Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
(20)Centre Expert Parkinson, Neurologie, CHU Henri Mondor, AP-HP, Equipe NPI,
IMRB INSERM Et Faculté de Santé, Université Paris-Est Créteil, Créteil, France.
(21)Département de Neurologie, Centre Hospitalier Universitaire François
Mitterrand, Université de Bourgogne, Dijon, France.
(22)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.
(23)Movement Disorders Department, Lille University, Inserm 1172, Lille, France.
(24)Department of Neurology, Limoges University Hospital, Inserm, U1094,
EpiMaCT-Epidemiology of Chronic Diseases in Tropical Zone, 87042, Limoges Cedex
01, France.
(25)Hospices Civils de Lyon, Pierre Wertheimer Neurological Hospital, Expert
Parkinson Center, Lyon University, Bron, France.
(26)Université Claude Bernard Lyon 1, Faculté de Médecine et de Maïeutique Lyon
Sud Charles Mérieux, Oullins, France.
(27)Marc Jeannerod Institute for Cognitive Neuroscience, CNRS, UMR 5229, Bron,
France.
(28)Movement Disorders Unit, Neurology Department, University Hospital of
Marseille, Marseille, France.
(29)EuroMov, Univ. Montpellier, Montpellier, France.
(30)Department of Neurology, CHRU Montpellier, Montpellier, France.
(31)Service de Neurologie, Centre Expert Parkinson, Centre Mémoire de Ressources
et de Recherche de Lorraine, Hôpital Central Nancy, Nancy, France.
(32)Service de Neurologie, CHU Nantes, INSERM, CIC, 1413, Nantes, France.
(33)Department of Neurology, Centre Hospitalier Universitaire de Nice,
Université Côte d’Azur, Nice, France.
(34)Department of Neurology, University Hospital of Nîmes, Nîmes, France.
(35)Departement of Neurology, Poitiers University Hospital, INSERM, CHU de
Poitiers, Centre d’Investigation Clinique CIC1402, Poitiers, France.
(36)Department of Neurology, Hôpital Maison Blanche, Reims, France.
(37)Department of Neurology, Pontchaillou University Hospital, CIC INSERM 1414,
Rennes, France.
(38)Department of Neurology, Rouen University Hospital and University of Rouen,
Rouen, France.
(39)Laboratory of Neuronal and Neuroendocrine Differentiation and Communication,
CEP Rouen, INSERM U1239, Mont-Saint-Aignan, France.
(40)Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg,
France.
(41)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.

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.

© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria,
part of Springer Nature.

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