Objective: To identify demographic, clinical, and genetic factors associated with the outcomes of amantadine treatment in dyskinetic Parkinson’s disease (PD) patients.
Background: While recent advancements have been made in PD pharmacotherapy, no new medications have been proposed for managing levodopa-induced dyskinesias (LID), and amantadine remains one of the few effective anti-dyskinetic treatments. However, the response to amantadine varies significantly among PD patients, making LID dyskinesia management a persistent challenge.
Method: We enrolled participants diagnosed with PD who had been treated with amantadine. The participants were classified into two main groups: ‘responders’ and ‘non-responders.’ The ‘non-responder’ group was further subdivided into two categories: ‘lack of efficacy’ and ‘side effects.’ Demographic, clinical, and blood/saliva samples for genetic testing were collected. Genotyping was performed using the Neurobooster array. Polygenic risk scores (PRS) for PD were calculated using PRSice-2, and pharmacogenomic variants previously associated with amantadine response or LID occurrence were assessed.
Results: Out of 146 participants, 88 provided biological samples. The mean age was 66.9 years, with 57.5% being male. The duration from PD diagnosis to initiation of amantadine was significantly longer in the responders cohort (median = 5.5 years vs. 3 years, p = 0.005). The average levodopa equivalent daily dose (LEDD) was also higher in responders (1057.6 mg, SD = 431.5) compared to non-responders (831.1 mg, SD = 504.7, p = 0.006). Among non-responders, the LEDD was higher in the group without side effects (1013.5 mg, SD = 613.6 vs. 725.2 mg, SD = 397.5, p = 0.015). Our genetic findings revealed a significantly higher proportion of the non-responders who were heterzygote for the rs4818 variant (OR = 1.41, p = 0.0141) and non-responders who were heterozygous for rs4704559 had 66% the odds of experiencing side effects of amantadine compared to non-responders without this variant present (OR = 0.655, p = 0.0090).
Conclusion: Our data indicate that the efficacy and tolerability of amantadine are influenced by various clinical factors, and patients may respond differently based on the presence of certain genetic variants. The generated PRS will be assessed and their potential association with amantadine response will be presented at the conference.
To cite this abstract in AMA style:
L. Saadatpour, H. Chaparro-Solano, J. Yu, C. Sonneborn, C. Piccinin, S. Anis, E. Assaedi, P. Coss, S. Horn, O. Vaou, I. Mata, H. Fernandez. Unraveling the Variability in Amantadine Response for Levodopa-Induced Dyskinesias: The Impact of Clinical and Genetic Factors [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/unraveling-the-variability-in-amantadine-response-for-levodopa-induced-dyskinesias-the-impact-of-clinical-and-genetic-factors/. Accessed November 20, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/unraveling-the-variability-in-amantadine-response-for-levodopa-induced-dyskinesias-the-impact-of-clinical-and-genetic-factors/