A 68-year-old man is started on levodopa-carbidopa for Parkinson's disease. After 6 years he develops marked wearing-off and peak-dose dyskinesias. Which pharmacological addition is best supported for reducing off-time without worsening dyskinesia?

• A Entacapone (COMT inhibitor) to extend levodopa bioavailability
• B Ropinirole as adjunct dopamine agonist to smooth out motor fluctuations
• C Selegiline MAO-B inhibitor to reduce levodopa catabolism
• D Amantadine extended-release to suppress dyskinesias and reduce off-time ✓

Explanation

Amantadine extended-release (AMANTREL ER / Osmolex ER) is the only FDA-approved therapy specifically indicated for levodopa-induced dyskinesias (LID), based on the EASE LID trial which showed significant reduction in on-time with troublesome dyskinesias. While entacapone and MAO-B inhibitors reduce off-time, they tend to increase dyskinesias. Dopamine agonists reduce off-time but also augment dyskinesias. Amantadine acts as an NMDA receptor antagonist, reducing glutamate-mediated synaptic plasticity underlying dyskinesias while maintaining dopaminergic stimulation for on-time.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.