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.
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.
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.
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).
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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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).
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.
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