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Journal of Pharmacy Practice, Vol. 21, No. 4, 254-261 (2008)
DOI: 10.1177/0897190008321846

Pharmacologic Options for Treatment of Levodopa-Associated ``Wearing Off''

Cheryl H. Waters, MD, FRCPC

Division of Movement Disorders, Department of Neurology, Columbia University Medical Center, New York, New York

Jack J. Chen, PharmD, BCPS, CGP

Movement Disorders Center, Schools of Medicine and Pharmacy, Loma Linda University, Loma Linda, California, jjchen{at}llu.edu

Levodopa remains the gold standard drug for the treatment of Parkinson's disease, but the combination of disease progression and prolonged treatment can lead to ``wearing-off'' problems in the majority of patients. This constitutes the onset of motor fluctuations which includes nonmotor sensory, psychiatric, and autonomic ``off '' symptoms. There are several pharmacologic options to minimize the ``wearing-off'' phenomenon, including adjustment of levodopa treatment, the use of long-acting dopamine agonists, monoamine oxidase type B inhibition, or catechol-O-methyl-transferase inhibition in combination with levodopa. Dopamine agonists may reduce levodopa requirements. Monoamine oxidase type B inhibition can increase dopamine availability by preventing its metabolism. Similarly catechol-O-methyl-transferase inhibitors can increase the half-life of levodopa and the amount available to cross the blood-brain barrier by preventing its breakdown. The selection of a treatment for the management of ``wearing off'' should consider the relief of symptoms and also the potential adverse effects of adjunctive therapy.

Key Words: Levodopa • motor complications • Parkinson's disease • rasagiline • selegiline


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