Levodopa fractionation in Parkinson's disease

Fractionation of daily levodopa dosage is one strategy to manage the almost inevitable development of symptom fluctuations in Parkinson's disease (PD). However, it is not known from the literature how levodopa fractionation is performed in routine clinical practice.

The objective of this study was to capture how anti-parkinsonian medications were used, in particular how the daily dose was fractionated (defined as >4 doses/day).

A pharmacoepidemiological study was undertaken at Uppsala University Hospital. Medical records of PD patients with ≥ 4 years' disease duration who visited the Neurology Clinic between January and October 2011 were retrospectively reviewed. Times to dose fractionation, to dyskinesias and to hallucinations were calculated using Kaplan-Meier analyses.

175 patients (47% women) were included. Median age at PD onset was 63 years (range 36-83). Median disease duration was 9.0 years. Dose fractionation was used in 85% of patients. The median time to fractionation was 5.0 years. Patients developing dyskinesias had a significantly earlier age at onset than those who did not.

Fractionation of levodopa dosage into >4 daily doses was common. It occurred when wearing-off of the levodopa response is expected to present, i.e. after 5 years in 50% of patients. The study highlights the importance of individualizing and frequently adjusting levodopa dosage, already from the initiation of therapy.