A 68-year-old man with 3-year history of Parkinson's disease controlled on levodopa-carbidopa develops dyskinesias (involuntary writhing movements) 2 hours after each dose of levodopa, coinciding with peak drug levels. His motor symptoms worsen before the next dose. What is the most appropriate pharmacological adjustment?
- A Increase the dose of levodopa per administration
- B Switch to a dopamine receptor agonist monotherapy
- C Reduce levodopa dose per administration and increase frequency, or add a COMT inhibitor ✓
- D Add a selective MAO-B inhibitor to the current unchanged regimen
Correct answer: C. Reduce levodopa dose per administration and increase frequency, or add a COMT inhibitor
Explanation
Peak-dose dyskinesias in Parkinson's disease result from pulsatile dopaminergic stimulation when plasma levodopa levels are at their highest. The strategy is to smooth dopaminergic stimulation by reducing the individual dose while increasing the frequency (fractionating the dose) to minimize peak levels. Adding a COMT inhibitor (entacapone) extends levodopa bioavailability and reduces wearing-off, but may worsen dyskinesias if the existing dose is not simultaneously reduced. Amantadine has antidyskinetic properties and may also be added.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.