Parkinson's disease: medical treatment of moderate to advanced disease

Parkinson's disease, a common neurodegenerative disorder, results in significant morbidity 10 to 15 years after disease onset and increased mortality. Levodopa is the mainstay of therapy and provides benefit for the duration of the illness. However, within 5 years, up to 50% of individuals develop fluctuations, including dyskinesias, wearing off, and "on/off" effects. Optimal management of Parkinson's disease patients requires careful titration of medications, with use of polypharmacy, including levodopa, dopamine agonists, catechol-O-methyltransferase inhibitors, amantadine, and anticholinergics in order to maintain good motor function and quality of life. With advancing disease, problems such as dysphagia, dysarthria, and gait and balance abnormalities occur, which are not responsive to dopaminergic medication. Due to extradopaminergic neuronal system degeneration, autonomic dysfunction can also be prominent. Recognition and management of these problems is helpful in improving quality of life in late-stage disease. In very late stages, dementia may complicate treatment, requiring discontinuation of combination therapy and use of low-dose levodopa with atypical neuroleptics.