A major limitation of present-day long-term drug therapy for Parkinsonism is:

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The decreased effectiveness of levodopa, also known as levodopa tolerance or "wearing off," is a major limitation of long-term drug therapy for Parkinsonism. Over time, patients may require higher doses or more frequent administration of levodopa to achieve the same therapeutic effect, which can lead to dyskinesia and other side effects. This can make it challenging to manage Parkinson's symptoms effectively while minimizing drug-related complications.

A Major Limitation of Present-Day Long-Term Drug Therapy for Parkinsonism