"On-off" effects in patients with Parkinson's disease on chronic levodopa therapy.

Fluctuations in performance in patients with Parkinson's disease on chronic levodopa therapy (the "on-off" effect) are due to several factors. The increasing severity during treatment of early morning akinesia, "freezing" episodes, and end-of-dose deterioration are probably due to progression of the underlying disease. Peak-dose dyskinesia and peak-dose akinesia are due to levodopa over dosage. "Yo-yo-ing", which is the severest form of such fluctuation in mobility and dyskinesias, may represent the sum of these disorders.