On-Demand Therapy for OFF Episodes in Parkinson's Disease

Levodopa is the most effective therapy for Parkinson's disease; however, chronic treatment is associated with the development of OFF episodes, in which there is a return of parkinsonian features following a dose of levodopa and prior to the onset of benefit from the subsequent dose. OFF episodes can be a major source of disability for PD patients and frequently result in depression, apathy and an unwillingness to participate in social activities. Most currently available medical and surgical therapies are designed to reduce total daily OFF time but do not provide a rapid and reliable "on-demand" therapy for individual OFF episodes. Indeed, responses to individual doses of levodopa during an acute OFF episode are unreliable, frequently leading to partial-ON, delayed-ON, or no-ON responses even at different times in the same patient. There are now 3 therapies that are available for the on-demand treatment of OFF episodes; subcutaneous injection of apomorphine, sublingual apomorphine film, and inhaled levodopa. The first has not enjoyed widespread use in the PD community, whereas the latter 2 therapies have only recently been approved. This review will consider the currently available on-demand therapies and their potential advantages and disadvantages. © 2021 International Parkinson and Movement Disorder Society.