A 70-year-old man with Parkinson's disease has been on levodopa/carbidopa for 8 years and now experiences predictable 'wearing-off' and unpredictable 'on-off' fluctuations. Which pharmacological strategy is MOST appropriate to address wearing-off?
- A Switch to apomorphine subcutaneous infusion only
- B Add a COMT inhibitor such as entacapone ✓
- C Add an anticholinergic agent
- D Reduce levodopa dose and add high-dose dopamine agonist
Correct answer: B. Add a COMT inhibitor such as entacapone
Explanation
COMT (catechol-O-methyltransferase) inhibitors like entacapone or tolcapone block peripheral COMT-mediated conversion of levodopa to 3-O-methyldopa, prolonging the half-life of levodopa and smoothing motor fluctuations. They are specifically indicated for wearing-off. MAO-B inhibitors (selegiline, rasagiline, safinamide) are an alternative. Anticholinergics are for tremor-predominant disease in younger patients and have significant cognitive side effects in elderly. Apomorphine infusion is for advanced refractory cases.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.