Levodopa remains today the most powerful drug available to treat PD. In fact, the absence of a robust response to high-dose levodopa essentially excludes the diagnosis of PD and suggests that there must be another explanation for the parkinsonian symptoms. In contrast, a marked and sustained response strongly supports the diagnosis of PD (55). Although numerous other treatment options are available in early PD when the disease is mild, virtually all patients will eventually require levodopa therapy as the disease worsens.
However, as mentioned above, not all symptoms of PD are equally responsive to levodopa. Bradykinesia and rigidity generally show the most dramatic improvement with dopaminergic therapy. In fact, the presence of residual rigidity is a good means by which to determine if a patient would further improve by increasing the dose. Tremor has a more variable (and often incomplete) response to levodopa. A number of other symptoms, including postural instability, micrographia, and speech disturbance, are typically poorly responsive to dopaminergic therapy; suggesting they are likely due to deficits in other neurotransmitter systems. Recognition of the differential responsiveness of these symptoms to levodopa is critical for setting realistic treatment goals.
Early in the course of disease, levodopa provides a long-duration response that can last several days even if levodopa is discontinued. This continuous response occurs in the presence of a short plasma half-life of a little more than 30 minutes (56,57).
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