Objective: To assess amantadine use in the French NS-Park cohort and factors associated with its prescription

Background: Amantadine, a unique dopamine/glutamate drug, is approved worldwide for the treatment of PD, including levodopa-induced dyskinesia (LIDs). Its prescription varies greatly according to countries and PD stages.

Method: Amantadine utilization was assessed in all PD patients with at least 1 visit (Jan 2016-Dec 2020) providing demographics, PD signs (MDS-UPDRS) and PD treatments data from the NS-Park prospective cohort of the 25 French PD Expert Centres (cross-sectional set; n=12,542). Longitudinal assessments were performed in a second set of patients including patients with ≥2 consecutive 12-month-interval visits (n=4,204) to assess factors associated with amantadine prescription at the first visit (before initiation). A case-control approach, including patients starting amantadine between 2 visits (n=119) versus never-exposed matched patients (n=238) was then performed to assess the impact of amantadine prescription at the second visit (after initiation) on motor fluctuations (MFs), LIDs and non-motor symptoms [apathy, freezing of gait (FoG), impulse control disorders (ICDs) and fatigue].

Results: 1,585/12,542 (12.6%) patients were exposed to amantadine in the cross-sectional analysis (median dose=200 mg). They were younger, with longer and more severe PD, and had more axial symptoms, MFs; LIDs and ICDs than non-exposed ones.  In patients with ≥2 visits, amantadine initiation was associated with the presence at the first visit of LIDs (OR: 4.05; CI 95%: 2.5-6.6), younger age (OR: 0.96; CI 95%: 0.9-0.8), higher levodopa equivalent daily dose (OR:1.7; CI 95%: 1.2-2.5) and freezing (OR: 1.58; CI 95%: 1.02-2.4) and lower cognitive impairment (OR: 2.1; CI 95%: 1.1-3.5) (multivariate analysis). Only 9 (0.002%) patients withdrew amantadine between 2 visits. In the case-control analysis, amantadine introduction was associated at the second visit with a reduction in MFs and LIDs (p=0.03). No effect was detected on other symptoms.

Conclusion: 12.6% of the French NS-Park PD patients were exposed to amantadine, mostly in those with more advanced PD and better cognitive profile. Amantadine initiation was associated with a subsequent reduction in motor fluctuations and LIDs.

References: Rascol O, Fabbri M, Poewe W. Amantadine in the treatment of Parkinson’s disease and other movement disorders. Lancet Neurol. 2021 Dec;20(12):1048-1056.
Rascol O, Negre-Pages L, Damier P, Delval A, Derkinderen P, Destée A, Fabbri M, Meissner WG, Rachdi A, Tison F, Perez-Lloret S; COPARK Study Group. Utilization Patterns of Amantadine in Parkinson’s Disease Patients Enrolled in the French COPARK Study. Drugs Aging. 2020 Mar;37(3):215-223.
Mariani LL, Doulazmi M, Chaigneau V, Brefel-Courbon C, Carrière N, Danaila T, Defebvre L, Defer G, Dellapina E, Doé de Maindreville A, Geny C, Maltête D, Meissner WG, Rascol O, Thobois S, Torny F, Tranchant C, Vidailhet M, Corvol JC, Degos B; NS-Park/F-CRIN Network study group. Descriptive analysis of the French NS-Park registry: Towards a nation-wide Parkinson’s disease cohort? Parkinsonism Relat Disord. 2019 Jul;64:226-234.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/utilization-pattern-and-factors-associated-with-amantadine-use-in-parkinsons-disease-pd-of-the-french-ns-park-cohort/