Switching dopamine agonists in advanced Parkinson's disease: is rapid titration preferable to slow?

Abstract

Background: New dopamine agonists are available, but no study has examined safe and effective ways to switch from one agonist to another.

Objective: To compare rapid- versus slow-titration schedules for starting a new dopamine agonist in patients already on chronic agonist therapy for Parkinson's disease.

Methods: Sixteen patients on stable carbidopa/levodopa and a dopamine agonist (bromocriptine or pergolide) switched to pramipexole using a conversion calculation of 1:1 for pergolide dose and 10:1 for bromocriptine dose. Patients were randomized to two titration schedules-either slow titration, following the package insert and taking up to 8 weeks to reach their equivalent dosage (8 patients), or rapid titration, receiving the full converted dose the day after stopping the former agonist (8 patients) with subsequent weekly dose adjustments. Using a blinded observer, the primary outcome variable was the time required to a Unified Parkinson's Disease Rating Scale (UPDRS) motor score superior to baseline without increased adverse effects.

Results: Both groups showed equivalent and statistically significant improvement after switching to the new agonist. The mean time to reach a UPDRS score that was superior to baseline without increased adverse effects was significantly shorter in the rapid-titration group (mean 2.1 weeks versus 5.3 weeks). Furthermore, with slow titration two patients experienced enhanced parkinsonian serious adverse effects requiring hospitalization (two falls with fractures).

Conclusion: The switchover from one agonist to another can be safely and successfully accomplished with a rapid titration based on an equivalency dose calculation.