Objective: Amantadine anecdotally improves gait and balance in PSP, potentially by increasing alertness, but there are no definitive data to support this observation. We investigated correlations between amantadine usage, gait, and cognition in PSP using longitudinal data from the 2014 davunetide trial.

Background: The davunetide trial, a randomized, double-blind, placebo-controlled, 52-week study, did not achieve its primary endpoints on the PSP Rating Scale (PSPRS) or SEADL[1]. It did provide a large, longitudinal dataset in PSP, including measures of amantadine usage, gait & balance, and cognition.

Method: We analyzed deidentified data at baseline, week 26, and week 52 for associations between the PSPRS-gait and midline subsection score, RBANS total, and RBANS-attention. We also examined differences in on vs off amantadine groups in RBANS total, RBANS-attention, PSPRS total, and the PSPRS-gait and midline subsection at baseline and week 52.

Results: 43 patients were on amantadine; 267 were not. RBANS total, RBANS-attention, PSPRS total, and PSPRS-gait and midline scores did not significantly differ between subjects taking amantadine and not taking amantadine at baseline or at week 52. RBANS total inversely correlated with PSPRS-gait and midline scores at baseline (r= -0.30, p<0.001), and this correlation became stronger over time (week 26: r= -0.37, p<0.001 week 52: r= -0.42, p<.001). However, the correlation between RBANS total and PSPRS total was even more significant over time (baseline: r= -0.50, p<0.0001 week 52: r= -0.61 p<0.0001).

Conclusion: This post hoc analysis of the davunetide trial dataset does not support the role of amantadine for symptomatic treatment of gait or cognition in PSP, but the trial was not powered to find such a difference. Also, the PSPRS does not include a measure of freezing of gait; this is relevant because some clinicians note freezing of gait responds to amantadine in a subset of PSP patients. Cognitive deficits strongly correlated over time with worsening of gait and balance in this population, but also with total PSPRS scores, likely reflective of overall disease progression.

References: [1] Boxer, A et al. Davunetide in patients with progressive supranuclear palsy: a randomized, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurology. 2014.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/correlations-between-amantadine-usage-gait-and-cognition-in-psp-a-post-hoc-analysis-of-the-davunetide-trial/