Dopamine agonists provide substantial improvement in PD symptoms while delaying the development of motor fluctuations and dyskinesia (32,42,58). Similar trials comparing dopamine agonists (pergolide, pramipexole, ropinirole) to levodopa in a randomized fashion suggest possible long-term benefit according to the functional imaging measures (2,3). The reduction in striatal and nigral decline in F-dopa and P-CIT uptake suggest these agents have some benefit over levodopa for up to 46 months of treatment. In a clinical setting of a 30-year-old patient, it is quite compelling to delay levodopa therapy in favor of a dopamine agonist because of the potentially long clinical horizon (59). Conversely, in an 80-year-old patient with other health concerns, treatment with levodopa may be better tolerated. The decisions regarding initial therapy in the 50 years between these two examples is dependent on the health of the patient, the side-effect profiles, and cost of the drugs (Table 2).
Dopaminergic medications have similar side effect profiles: nausea, sleepiness, confusion, orthostatic hypotension, and hallucinations among others (Table 2). Besides these problems, lower extremity edema, hair loss, and weight gain have also been seen with dopamine agonist use. The ergoline-derivatives, bromocriptine, cabergoline, and pergolide, also have a slight risk of erythromelalgia and pulmonary and retroperitoneal fibrosis, which have been reported in 2% to 5% of patients exposed to these agents (1). With all dopaminergic agents, it is possible that excessive daytime sleepiness, unexpected sleep episodes, and reduced impulse control leading to behaviors such as pathological gambling could occur in a small percentage of patients (34-39). Therefore, patients should be educated to be vigilant of these potential side effects and notify their physician if they occur. The side effects of these agents are quite similar, but vary from patient to patient, so it is important for a patient to understand that if he or she does not tolerate the first dopamine agonist; there is no reason to expect that none of the medications in this class will provide benefit.
Initiation of dopamine agonist therapy is somewhat dependent on the needs and emotional state of the patient. Each of the dopamine agonists requires a titration period from four to eight weeks (Table 3). In the healthy patient seeking to improve quickly, initiation of a rapidly titrated agent may be preferred, whereas the more slowly titrated schedules may suit the needs of a patient reluctant to take any drugs. Each patient should be reminded that the differences in titration time usually are less than three weeks, a brief period of time in the context of a 20-year treatment horizon.
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