Topic Overview

Movement problems (motor fluctuations) are the most common complication of long-term levodopa use. The majority of people who take levodopa develop these problems within 5 to 10 years. The main types of levodopa-related motor fluctuations include:

• The wearing-off effect. Wearing-off periods occur when the effects of a single dose of levodopa do not last as long as they used to. Control of motor symptoms decreases as the effects of the medicine wear off, and symptoms do not improve until the next dose of levodopa is taken. These motor fluctuations are easy to predict based on the timing of each dose of medicine.
• Dyskinesias. Dyskinesias are sudden, uncontrollable, often jerky or writhing movements. They may affect the head, neck, arms, and legs, or other parts of the body. Dyskinesias are especially common in younger people with Parkinson's disease.
• The on-off response. "On" and "off" periods occur without warning as a result of fluctuating dopamine levels in the brain. The symptoms are similar to the motor problems that occur as a result of the wearing-off effect, but they are harder to predict and more difficult to treat. An "off" period usually occurs suddenly, over seconds or minutes, and the person may freeze. In contrast, uncontrollable movements may occur during the "on" periods.

Motor fluctuations sometimes can be reduced or delayed by changing the schedule and amount of levodopa. Other medicines may be added to levodopa to help with motor fluctuations, such as dopamine agonists, COMT inhibitors, or MAO-B inhibitors. Increasingly, doctors are using dopamine agonists for initial treatment of Parkinson's disease, especially in younger people, to delay the development of motor fluctuations that eventually occur with long-term levodopa therapy.