Pharmacological Treatment of Early Motor Manifestations of Parkinson Disease (PD)

Abstract

Parkinson disease (PD), as a slowly progressive neurodegenerative disorder, undergoes six neuropathological stages. The earliest clinical manifestation presents in the middle stage of the disorder pathologically, when 50% or more of the dopaminergic neurons have degenerated in the substantia nigra. This discrepancy between the early stage clinically and that pathologically has, in part, spurred the debate as to when it is best to initiate symptomatic therapy. The most well-studied monotherapeutic agents for PD in its early course include levodopa (the cornerstone of PD therapy), dopamine agonists, and monoamine oxidase inhibitors (MAOIs). With several options for initiating pharmacologic therapy, along with the heterogenous presentation of the disorder, an individualized approach is warranted. Careful deliberation must be done to optimize risk reduction while providing effective symptom control, taking the chronological age, comorbidities, social and financial disposition, work status, and both immediate- and long-term goals into consideration. Generally, treatment can be delayed in patients with mild symptoms and minimal functional impairment at any age. If treatment must be initiated, dopamine agonists and monoamine oxidase type B inhibitors can be used, especially in younger patients with milder disease. However, for older patients, those with moderate to severe PD symptoms, regardless of age, or for patients with greater comorbidities, levodopa generally remains the better choice. Eventually, regardless of initial therapy, studies have shown that most will eventually require levodopa therapy when symptoms become more disabling.