Management of Parkinson Disease: Defining the Role of Ropinirole
Parkinson disease is a movement disorder caused by progressive dopaminergic neuron degeneration in the substantia nigra and characterized by four cardinal symptoms: resting tremor, bradykinesia, rigidity, and postural instability. Levodopa has been considered the first-choice intervention for Parkinson disease for more than three decades. However, up to 50–90% of levodopa-treated patients develop motor complications within 5–10 years of starting treatment. It is important, therefore, to delay the initiation and/or reduce the dosage requirements of levodopa. The non-ergoline dopamine agonist ropinirole (Requip®) is used as monotherapy or in combination with low-dose levodopa in patients with early disease, and as an adjunct to levodopa in patients with advanced Parkinson disease.
As an adjunct to levodopa therapy in patients with more advanced disease, ropinirole is generally more effective than bromocriptine and more effective than placebo. Ropinirole (with or without levodopa) is more effective than placebo and at least as effective as bromocriptine when administered as therapy for early Parkinson disease. It reduces the risk of dyskinesia relative to levodopa and maintains long-term control of the underlying disease symptoms, factors that are associated with improved functional ability. Ropinirole reduced the loss of putamen dopamine storage capacity compared with levodopa in a functional imaging study. However, it was unclear whether this resulted from any neuroprotective activity of ropinirole; further research is required to identify any clinically important neuroprotective activity of dopamine agonists. Ropinirole has a tolerability profile generally similar to that of bromocriptine and levodopa when used as monotherapy. In common with all dopaminergic agents, ropinirole has been linked with sedation and unintended sleep episodes; however, these effects may also result from the underlying disease process in patients with Parkinson disease.
Only limited data are available from pharmacoeconomic evaluations of ropinirole. Nevertheless, a cost-minimization analysis indicates that, from a societal viewpoint in Canada, ropinirole is cost saving relative to treatment with levodopa plus a dopa decarboxylase inhibitor in patients with early Parkinson disease. Further economic and quality-of-life assessments of ropinirole are required, particularly comparisons with other dopamine agonists and antiparkinsonian interventions.
In conclusion, ropinirole is established as an adjunct to levodopa in advanced Parkinson disease, and as monotherapy or in combination with low-dose levodopa in early disease. It is in the setting of early Parkinson disease that ropinirole may see greatest expansion of its overall role in disease management programs.