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Utilization Patterns of Amantadine in Parkinson’s Disease Patients Enrolled in the French COPARK Study

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Abstract

Introduction

Immediate-release (IR) amantadine has been marketed for Parkinson’s disease (PD) therapy for 50 years, while two novel extended-release formulations have only recently reached the market in the US.

Objectives

The aim of this study was to describe amantadine IR utilization patterns in the French COPARK cohort, at baseline and after 2 years of follow-up.

Methods

Overall, 683 PD patients from the COPARK survey were evaluated. All patients were assessed in a standardized manner (demographics, treatments, Unified Parkinson’s Disease Rating Scale [UPDRS], Hospital Anxiety and Depression Scale, Pittsburg Questionnaire and health-related quality-of-life scales (Short Form-36 [SF-36], 39-item Parkinson’s Disease Questionnaire [PDQ-39]). Longitudinal data were only available for 401/683 patients (59%) with a median (P25–75) follow-up period of 23 months (18–31). Patients were assessed in the same way as in the baseline visit.

Results

At baseline, amantadine was prescribed to 61/683 (9%) patients (median dose 200 mg/day, range 100–300 mg/day). Amantadine was initiated after a median of 7 years from PD diagnosis, and its prescription was correlated with the presence of dyskinesia (logistic regression odds ratio [OR] 3.72, 95% confidence interval [CI] 1.95–7.08) and hallucinations (UPDRS I.2) [OR 1.57, 95% CI 1.08–2.29]. After 2 years, the amantadine prescription increased from 33 (8%) patients at baseline to 54 (14%) patients in the subset of 401 patients analysed twice (p = 0.001). Among the 33 patients receiving amantadine at baseline, 9 (27%) stopped amantadine, 5 (15%) increased the dose, 6 (18%) reduced the dose and 13 (40%) stayed at the same doses. Treatment was initiated in 30/54 new patients (55%). Patients who started amantadine or increased its dose (n = 35) had more levodopa-induced dyskinesias at baseline (OR 7.02, 95% CI 3.09–15.90) and higher Mini-Mental State Examination score at follow-up (OR 1.37, 95% CI 1.06–1.79). Undergoing deep brain stimulation was related to stopping or downtitrating amantadine (OR 22.02, 95% CI 4.24–114.44; n = 15).

Conclusions

In this cohort, amantadine was used in 10% of patients. Its use increased during follow-up, despite the fact that one-third of patients who received amantadine at baseline stopped taking it. Amantadine prescription was mainly correlated with the presence of dyskinesia.

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Acknowledgements

The authors thank the patients who agreed to participate in this study and the Association France-Parkinson for its support. The COPARK study group included Dr. F. Tison (Bordeaux); Dr. E. Gaujard, Dr. E. Puymirat, Dr. A. Lanusse, Dr. C. Delabrousse-Mayoux, Dr. E. Goumard, Dr. M.H. Godin, Dr. P. Damier (Nantes); Dr. P. Lejeune, Dr. B. Philippe, Dr. C. Lanctin-Garcia, Dr. V. Verbist-Talmant, Dr. Rascol (Toulouse); Dr. B. Robinson, Dr. V. Rey-Zermati (Narbonne); Dr. X. Soulages (Rodez); Dr. C. Azais-Vuillemin (Toulouse); N. Stambouli (Cahors); Dr. J.R. Rouane (Toulouse); Dr. A.M. Salandini (Toulouse); Dr. J.M. Boulesteix (Cahors); Dr. M. Barreda (Castres); Dr. D. Castan (Castres); Dr. A. Ojero-Senard (Toulouse); Dr. S. Perez-Lloret (Toulouse); Dr. G. Angibaud (Montauban); Dr. J.P. Balague (Montauban); Dr. A. Danielli (Montauban); Dr. K. Attane (Carcasonne); Dr. J.M. Faucheux (Castres); Dr. P. Henry (Toulouse); Dr. M.G. Rougie (Toulouse); Dr. R. Darmanaden, Dr. B. Jardillier (Figeac); Dr. F. Bonenfant (Toulouse); Dr. Azais (Toulouse); Dr. Damase (Toulouse) and Dr. A. Destee (Lille).

Author information

Authors and Affiliations

  1. Centre d’Investigation Clinique CIC 1436, Services de Pharmacologie Clinique et Neurosciences, NS-Park/FCRIN Network, NeuroToul COEN Center, Université de Toulouse UPS, CHU de Toulouse, INSERM Toulouse, Toulouse, France

    Olivier Rascol & Amine Rachdi

  2. LN Pharma, Toulouse, France

    Laurence Negre-Pages

  3. Unité de Recherche Clinique et Epidémiologie, Département d’Information Médicale, Hôpital la Colombière, Montpellier, France

    Laurence Negre-Pages

  4. CHU de Nantes, INSERM, CIC 1413, Department of Neurology, NS-Park/FCRIN Network, Université de Nantes, Nantes, France

    Philippe Damier & Pascal Derkinderen

  5. CHU de Lille, INSERM, Department of Neurology, U 837, NS-Park/FCRIN Network, Université de Lille, Lille, France

    Arnaud Delval & Alain Destée

  6. Department of Neuroscience, University of Turin, Turin, Italy

    Margherita Fabbri

  7. Service de Neurologie, CHU de Bordeaux, NS-Park/FCRIN Network, 33000, Bordeaux, France

    Wassilios G. Meissner & François Tison

  8. Institut des Maladies Neurodégénératives, CNRS, UMR 5293, Univ. de Bordeaux, 33000, Bordeaux, France

    Wassilios G. Meissner & François Tison

  9. Department of Medicine, University of Otago, Christchurch, New Zealand

    Wassilios G. Meissner

  10. New Zealand Brain Research Institute, Christchurch, New Zealand

    Wassilios G. Meissner

  11. Institute of Cardiology Research, University of Buenos Aires, National Research Council (CONICET-ININCA), Buenos Aires, Argentina

    Santiago Perez-Lloret

  12. Department of Physiology, School of Medicine, University of Buenos Aires (UBA), Buenos Aires, Argentina

    Santiago Perez-Lloret

  13. Department of Clinical Pharmacology, Faculty of Medicine, 37 Allées Jules Guesde, 31000, Toulouse, France

    Olivier Rascol

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  1. Olivier Rascol
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  2. Laurence Negre-Pages
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  10. François Tison
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for the COPARK Study Group

Corresponding author

Correspondence to Olivier Rascol.

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Funding

This project was co-funded by unrestricted and unconditional grants from the Association France-Parkinson, ADREN, Boehringer Ingelheim, Eisai, Faust Pharmaceuticals, GlaxoSmithKline, Pierre Fabre Médicaments, Solvay Pharma, and Wyeth Lederlé. The project was sponsored and co-financed by LN PHARMA, which participated in the design and conduct of the study; collection, management, and interpretation of the data; and preparation and review of the manuscript.

Conflict of interest

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 and Zambon) and has received unrestricted scientific grants from academic non-profit entities (Toulouse University Hospital, French Health Ministry, MJFox Foundation, France-Parkinson, European Commission). Laurence Negre-Pages reports grants from the Association France-Parkinson, ADREN, Boehringer Ingelheim, Eisai, Faust Pharmaceuticals, GlaxoSmithKline, Pierre Fabre Médicaments, Solvay Pharma and Wyeth Lederlé for funding this project. She also owns stock options from LN PHARMA, which was one of the sponsors of this study. Philippe Damier has received honoraria for conferences from Teva and Novartis. Wassilios Meissner reports receiving a grant from the Bordeaux University Hospital for this project. Outside the present work, he has received fees for editorial activities with Springer, consultancy activities from Affiris, Biohaven, Lundbeck and Sanofi, teaching honoraria from UCB, Boehringer Ingelheim and MDS, and research support from the Michael J Fox Foundation, the University Hospital Bordeaux, the French Health Ministry, the European Community, ANR, ARAMISE, PSP France, MSA Coalition, ARAMISE and LABEX Excellence Initiative. Santiago Perez-Lloret has received honoraria from Osmotica. Arnaud Delval, Pascal Derkinderen, Alain Destée, Margherita Fabbri, Amine Rachdi and Francois Tison have no conflicts of interest to declare.

Additional information

The members for the COPARK Study Group are listed in the Acknowledgements section.

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Rascol, O., Negre-Pages, L., Damier, P. et al. Utilization Patterns of Amantadine in Parkinson’s Disease Patients Enrolled in the French COPARK Study. Drugs Aging 37, 215–223 (2020). https://doi.org/10.1007/s40266-019-00740-2

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