Medication Strategies for Slowing the Progression of Parkinson’s Disease

Abstract

The recognition that levodopa therapy is capable of reversing the symptoms and signs of Parkinson’s disease (PD) revolutionized the treatment of this disorder. It was soon recognized, however, that the disease continues to progress despite levodopa treatment. This progression is not rapid but occurs over many years. Potentially, there are three avenues of progression, and they occur to variable degrees (Table 7-1). In the first are levodopa treatment complications, including motor fluctuations and involuntary movements (dyskinesias). These motor fluctuations reflect a short-duration response to a dose of levodopa, with the improvement in motor symptoms lasting from 1 hour to a few hours and then “wearing off.” A transition from one state to the other may occur very rapidly in some patients; this has been termed the “on-off’ response. These levodopa treatment complications typically occur later in the course of the disease, at least in most cases. The second avenue of progression is a declining motor response to levodopa therapy; treatment may become much less effective with the passage of time. This is not necessarily a problem for all patients, and many have a relatively preserved levodopa response that persists for many years. The third avenue of progression is the development of problems not related to motor control. Dementia occurs in approximately 10% to 30% of patients with advancing disease. Psychosis may also develop with advancing disease, occurring as delusions, hallucinations, or inappropriate behavior. This may be provoked by medications, but in some cases psychosis is independent of drug therapy. Symptoms of dysautonomia, which may be present to a mild degree early in the course,