The impact of early versus late levodopa administration

Abstract

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.

Protein-Restricted Diets for Ameliorating Motor Fluctuations in Parkinson's Disease

“…For instance, a retrospective analysis on 170 PD patients found early levodopa administration was related with an earlier onset of motor fluctuations from onset of PD, suggesting the need to delay the initiation of levodopa therapy in parkinsonians (Yahalom et al, 2016). On the other hand, a large open-label randomized trial in newly-diagnosed PD patients showed small but persistent benefit from initial treatment with levodopa, compared with initial treatment with a dopamine agonist or a MAO-B inhibitor (i.e., levodopa-sparing therapy; Gray et al, 2014).…”

“…Though levodopa provides the greatest symptomatic benefit for PD, there is an ongoing debate whether the initiation of levodopa therapy should be delayed to postpone the onset of levodopa-associated motor complications (Cilia et al, 2014 ; Connolly and Lang, 2014 ; Gray et al, 2014 ; Lang and Marras, 2014 ; Kalia and Lang, 2015 ; Yahalom et al, 2016 ). For instance, a retrospective analysis on 170 PD patients found early levodopa administration was related with an earlier onset of motor fluctuations from onset of PD, suggesting the need to delay the initiation of levodopa therapy in parkinsonians (Yahalom et al, 2016 ). On the other hand, a large open-label randomized trial in newly-diagnosed PD patients showed small but persistent benefit from initial treatment with levodopa, compared with initial treatment with a dopamine agonist or a MAO-B inhibitor (i.e., levodopa-sparing therapy; Gray et al, 2014 ).…”