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Levodopa with a decarboxylase inhibitor, dopamine agonists, MAO-B and COMT inhibitors
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- Levodopa with carbidopa or benserazide: the most effective. The decarboxylase inhibitor does not cross the blood-brain barrier, so it prevents peripheral conversion, reducing nausea and hypotension and allowing a lower dose
- Dopamine agonists (ropinirole, pramipexole, rotigotine): used to delay levodopa in younger patients. Notable for impulse control disorders (gambling, hypersexuality), hallucinations and somnolence
- MAO-B inhibitors (selegiline, rasagiline): mild benefit, useful early
- COMT inhibitors (entacapone): extend the levodopa effect, used for wearing off
- Amantadine: for dyskinesia
- Antimuscarinics (procyclidine): mainly for tremor and for drug-induced parkinsonism; avoid in the elderly
Long-term levodopa complications are the central problem: motor fluctuations with wearing off and unpredictable on-off phenomena, and dyskinesias. These drive the strategy of delaying levodopa in younger patients while using it early in the elderly, where quality of life over the remaining years matters more.
Never stop antiparkinsonian medication abruptly, including on admission or when nil by mouth, because of the risk of an akinetic crisis and neuroleptic malignant-like syndrome. Metoclopramide and antipsychotics are contraindicated; domperidone is the antiemetic of choice.