The goal of medical management of Parkinson's disease (PD) is to control signs and symptoms for as long as possible while minimizing side effects. Medical therapy generally provides good control of symptoms for 4 to 6 years.26 After this, disability progresses despite best medical management, and many patients develop long-term motor complications, including motor fluctuations and dyskinesia.15,46 Other causes of disability in late disease are postural instability (balance difficulty) and dementia. A major goal of current research is the discovery and development of new treatments to improve long-term outcome. At the same time, consideration must be given as to how to use best currently available medications to optimize control of signs and symptoms over the entire course of the disease. The selection, timing, dose, and order of medication administration in early disease may influence long-term outcome. Few definitive answers are currently available from long-term clinical trials. Therefore much of the impetus behind early treatment strategies is derived from theoretic considerations, basic science and animal model research, and retrospective and open-label patient studies. Neuroprotective therapies are defined as those that slow neuronal loss and thereby delay clinical disability. If a neuroprotective therapy were available for PD, it would be administered from the time of diagnosis onward. Although no currently available medication stops the progression of PD, there is interest as to whether selegiline can slow neuronal loss and delay clinical disability.70,73 l-Dopa and peripheral decarboxylase inhibitor (PDI) (Sinemet) therapy remains the gold standard of symptomatic treatment for PD. It provides the greatest antiparkinsonian benefit with the fewest side effects. Although dopamine agonists provide symptomatic benefit comparable to l-dopa/PDI in early disease, they lack sufficient antiparkinsonian efficacy to control signs and symptoms by themselves in later disease.52,86,87,88,90 These advantages of l-dopa/PDI are counterbalanced, however, by concern that it might accelerate disease progression or contribute to the development of motor fluctuations and dyskinesia.15,39,58,66 Thus, the two major questions in the treatment of early PD are: (1) Does selegiline slow neuronal loss and delay the progression of clinical disability? and (2) Should dopamine agonists be used as initial symptomatic therapy in early disease rather than l-dopa/PDI to reduce long-term disability and delay the onset of motor fluctuations and dyskinesia?

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