The impact of early versus late levodopa administration

Long-term levodopa therapy in patients with Parkinson's disease (PD) is associated with motor complications including motor fluctuations (MF) and levodopa-induced dyskinesias (LID). The time to appearance of MF and LID is apparently related to both the timing and the duration of levodopa therapy, but is highly variable. We performed a retrospective analysis of all levodopa-treated PD patients to explore the effect of time from PD onset to levodopa initiation on time to MF or LID. We used a Cox multivariate regression model after stratifying patients into four quartiles, according to the time to levodopa initiation. Data from 170 PD patients (117 males, age at onset: 65.1 ± 11.6 years, time to levodopa treatment: 23.8 ± 28.4 months) was included in the analysis. Early levodopa administration was associated with a shorter time from diagnosis to both MF (p < 0.001) and LID (p = 0.001). The hazard ratio to develop MF and LID from the time of PD diagnosis was 2.48 (p < 0.001) and 2.71 (p = 0.002), respectively. In our population, we found that delaying levodopa administration was associated with a longer time to the appearance of motor complications after diagnosis. While disease duration is the most important determinant of the onset of motor complications, delaying levodopa could prolong the 'complication-free' period.