Management of motor complications in Parkinson's disease

Motor fluctuations in Parkinson's disease (PD) typically develop after 4-6 years of therapy, and affect approximately half of all patients. The wearing-off effect is the most common type, and "delayed-on," "no-on," and "on-off" effects, as well as dyskinesias, may also develop as the disease progresses. Collectively, motor fluctuations represent a significant source of disability in advanced PD patients, and their mitigation is a major goal of patient management. Adjunctive medications, including dopamine agonists, amantadine, MAO-B inhibitors, and COMT inhibitors, each may reduce the frequency or duration of "off" periods, but none does so completely, and each contributes its own side effects which may limit optimal dosing. Surgery is another strategy to reduce "off" time, and both pallidotomy and deep brain stimulation of the globus pallidus or the subthalamic nucleus have been shown to be highly effective in this regard. However, surgery may be contraindicated in elderly advanced patients who could most benefit from its effect on "off" time. The unmet need for treatment of "off" episodes suggests the potential utility of an agent such as apomorphine injectable, which can reliably trigger an "on" response within 10-15 minutes of injection.