Delayed-Release/Extended-Release Amantadine for Dyskinesia and Off Time in Parkinson Disease

This segment focuses on treatment options for the 54-year-old woman with Parkinson disease and dyskinesia, emphasizing how the presence of “off” time significantly influences therapeutic decision-making. The patient's favorable clinical profile, including younger age, good cognitive function, and absence of hallucinations, psychosis, or impulse control disorders, opens up multiple treatment possibilities. The discussion reinforces that if the patient has minimal “off” time, medication reduction would be the preferred initial approach, but if “off” time is present, treatment strategies must shift to address both complications simultaneously.

The conversation highlights amantadine delayed-release/extended-release as a unique therapeutic option, being the only FDA-approved medication for treating both dyskinesia and “off” time. This formulation differs significantly from immediate-release amantadine, which has shown efficacy for dyskinesia in early studies but has never demonstrated improvement in “off” time. The delayed-release/extended-release formulation utilizes sophisticated pharmacokinetics, taken at bedtime with delayed release occurring after sleep onset to avoid sleep interference. The medication maintains therapeutic levels throughout the day through extended-release pellets, with levels gradually declining while sustaining efficacy.

Clinical trial data demonstrates robust efficacy for delayed-release/extended-release amantadine, showing approximately 40% reduction in dyskinesia scores on the unified dyskinesia rating scale (about 10 points) and increasing good “on” time by 2.4 hours. This improvement comprises 1 hour of “off”-time reduction and 1.4 hours of troublesome dyskinesia reduction. For the presented case, this medication represents an ideal treatment choice since it addresses both her likely “off” time (which further questioning would probably reveal) and her troublesome dyskinesia simultaneously. Alternative approaches such as reducing ropinirole or rasagiline would only worsen her motor symptoms if “off” time is present, making delayed-release/extended-release amantadine the optimal therapeutic intervention for her complex symptom profile.