Present and future directions in the management of motor complications in patients with advanced PD

Current medical therapies for PD are extremely effective in managing the early stages of the disorder. However, the management of advanced PD is complex, and important unmet medical needs remain. Despite the many benefits of dopaminergic therapy, long-term treatment is associated with motor complications in the majority of patients. Advances in the ability to prevent and treat these problems are the major focus of this review. Other important unmet medical needs in the management of advanced PD, including neuropsychiatric problems, dementia, freezing, postural instability, autonomic dysfunction, and other nonmotor problems, are also important sources of disability for many PD patients. These issues, however, are beyond the scope of this article and are extensively reviewed elsewhere.1

The vast majority of PD patients who receive l-dopa treatment for more than 10 years experience motor complications in the form of fluctuating motor responses and dyskinesia (table 1). This is particularly problematic for patients less than 60 years of age, who ultimately develop these problems in almost every case. In the extreme, patients can experience disabling dyskinesia during the l-dopa “on” period and severe akinesia during the l-dopa “off” phase. For these patients, periods of good motor function without dyskinesia may be difficult to achieve. Therefore, despite the proven antiparkinsonian benefits of l-dopa, patients with advanced PD may cycle between disabling “on” and “off” states for the majority of each day. Current medical approaches to the treatment of l-dopa-induced motor complications include manipulation of the levodopa dose and frequency, dopamine agonists (DAs), long-acting formulations of levodopa, catechol-O-methyl transferase (COMT) inhibitors, monoamine oxidase-B (MAO-B) inhibitors, and N-methyl-d-aspartic acid (NMDA) receptor antagonists. These treatments can provide benefit to individual patients, particularly when motor complications are relatively mild, but they are often ineffective for patients with …