Associations Between Amantadine Usage, Gait, and Cognition in PSP: A post-hoc Analysis of the Davunetide Trial.

Adam L Boxer,Amie L Hiller,Barbara H Brumbach,Marian L Dale

doi:10.3389/fneur.2020.606925

Abstract

Introduction: Amantadine anecdotally improves gait in progressive supranuclear palsy (PSP) but definitive data is lacking. We investigated associations between amantadine usage, gait, cognition, and activities of daily living in 310 subjects with PSP using data from the davunetide trial.Method: We compared baseline demographics, PSP Rating Scale (PSPRS), Repeat Battery for the Assessment of Neuropsychological Status (RBANS), and Schwab and England Activities of Daily Living (SEADL) scores between subjects taking vs. not taking amantadine using chi-square tests for categorical variables and independent sample t-tests for continuous variables. Using the general linear model (GLM), we tested whether group status predicted total PSPRS, PSPRS-gait and midline, total RBANS, RBANS-attention, and SEADL before and after the 52-weeks follow-up.Results: Subjects taking vs. not taking amantadine were similar at baseline, except subjects taking amantadine had a higher Clinical Global Impression (CGI) Score (p = 0.01). However, the CGI change score did not differ between groups at week 52 (p = 0.10). Using GLM models (controlling for covariates), we found that subjects taking vs. not taking amantadine did not significantly predict total PSPRS, PSPRS-gait and midline, total RBANS, RBANS-attention, or SEADL at baseline, week 52, or the change score between baseline and week 52.Discussion: This post-hoc analysis of the davunetide trial did not find an association between amantadine and gait or cognitive measures in PSP, but was not powered to find such a difference. Future studies should still examine amantadine for symptomatic benefit in multiple PSP subtypes.

Highlights

Amantadine anecdotally improves gait in progressive supranuclear palsy (PSP) but definitive data is lacking
The only notable group difference was that the group on amantadine had a higher Clinical Global Impression (CGI) score at baseline, indicative of more severe illness (Table 1)
Taking and not taking amantadine group differences within the davunetide and placebo groups were examined at week 52 for Schwab and England Activities of Daily Living (SEADL), CGI, Clinical Global Impression-Change (CGI-C), PSP Rating Scale (PSPRS) total, Repeatable Battery for Neuropsychological Status (RBANS) total, PSPRS total change score, and RBANS total change score (Table 1)

Summary

Introduction

Amantadine anecdotally improves gait in progressive supranuclear palsy (PSP) but definitive data is lacking. In a retrospective case review of 14 patients with PSP, Rajput found 43% showed improved bradykinesia or rigidity on amantadine, but gait and balance were not assessed [4]. In a retrospective review of 16 patients with PSP, Jackson et al found that of seven patients treated with amantadine, only one displayed improved parkinsonian symptoms overall, and six either showed no change or worsened [5]. Kompoliti et al examined clinical records of 12 autopsy-confirmed PSP cases and found that five of 12 patients received amantadine [6]. Two of those five demonstrated modest improvement of parkinsonism (both patients) and neck dystonia (one patient). Overall, existing retrospective reviews of amantadine in PSP are mixed and find that a subset of patients’ parkinsonian symptoms respond to amantadine

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