A 55-year-old man with Parkinson's disease develops 'on-off' fluctuations despite optimized levodopa and a dopamine agonist. He experiences painful 'off-period' dystonia. Which add-on therapy works by inhibiting catechol-O-methyltransferase (COMT) to prolong levodopa duration?

• A Selegiline
• B Amantadine
• C Apomorphine
• D Entacapone ✓

Explanation

Entacapone (and tolcapone) are peripheral COMT inhibitors that reduce the peripheral breakdown of levodopa to 3-O-methyldopa, thereby increasing plasma levodopa half-life by approximately 30–50% and reducing 'off' periods. Selegiline is a selective MAO-B inhibitor that reduces dopamine breakdown in the brain. Amantadine is an NMDA antagonist used primarily for levodopa-induced dyskinesias. Apomorphine is a non-ergot dopamine agonist used as a subcutaneous rescue injection for severe 'off' episodes. Entacapone must always be co-administered with levodopa/carbidopa.

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

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Written and medically reviewed by the StethoPrep medical team.