Pulsatile or continuous dopaminomimetic strategies in Parkinson's disease

Abstract

Levodopa is the most effective treatment for Parkinson's disease (PD) for both motor and non-motor control. Pulsatile levodopa administration likely contributes to the development of motor fluctuations and dyskinesia after a few years. All studies comparing levodopa versus dopamine agonist early therapy indicate that initiation with agonists is associated with a reduced risk of motor complications - in particular, dyskinesias - possibly because agonists' longer half-lives provide continuous dopaminergic delivery. Indeed, this therapeutic strategy may delay the emergence of motor fluctuations and dyskinesia which is essential to maintaining satisfactory quality of life. In advanced disease various levodopa-based strategies may be tried to control motor complications, such as dose fragmentation (smaller, more frequent dosing) or the use of orally administered, liquid levodopa formulations that may reduce off-time intervals or facilitate absorption. More recently introduced, continuous levodopa delivery by duodenal infusion (but also apomorphine infusion) may represent a more effective approach to treat motor complications in advanced PD, and its effect can be perceived by improvement both in clinical scales as well as in health-related items. Infusion therapies may reverse motor complications in complicated patients with significant benefit on quality of life.