Extended-release amantadine for OFF-related dystonia in Parkinson's disease

Abstract

Introduction: Dystonia is a painful OFF-related complication in Parkinson's disease (PD) with limited treatment options.

Methods: Post-hoc analysis using pooled data from two extended-release amantadine pivotal trials and follow-on open-label extension. Dystonia was assessed using the Unified Dyskinesia Rating Scale (UDysRS) Part 2 and the Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) item 4.6.

Results: Of 196 participants, 119 (60.7%) reported OFF-related dystonia at baseline per UDysRS. Twelve-week treatment with extended-release amantadine improved OFF dystonia (treatment differences vs placebo: UDysRS Part 2, -1.0 [-1.9,-0.1]; p = 0.03 and MDS-UPDRS Item 4.6, -0.3 [-0.6,-0.05]; p = 0.02). There was no correlation between changes in OFF time and changes in OFF dystonia. Double-blind improvements in OFF dystonia were sustained throughout the 2-year follow-up.

Conclusions: Extended-release amantadine yielded a sustained reduction in OFF-related dystonia in PD patients that was independent from a reduction in OFF time. A randomized controlled trial is warranted to confirm these findings.

Keywords: Amantadine; Dystonia; OFF; Parkinson's disease.