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.