Systematic evaluation on influence of dopaminergic therapy: on motor complications in Parkinson's disease

Abstract

To investigate the impact of dopaminergic therapy on the onset of motor complications in Parkinson's disease (PD). Two clinical questions were identified. (1) Whether levodopa (LD) dose, LD treatment duration, the time from disease onset to initiation of LD can predict the onset of motor complications in PD? and (2) whether dopamine agonists (DA) used in de novo patients can delay the onset of motor complications? Literatures on observation studies of factors associated with motor complications and randomized controlled trials (RCTs) of DA compared to LD in treatment of de novo patients published before May 2008 were retrieved from Pubmed, EMbase, and Cochrane Database. Methodology quality was critically assessed. 12 articles on the first question were selected, including one RCT, five cohort studies, six case-control studies. Six RCTs on the second question were selected. Because of clinical heterogeneity among the researches thus retrieved, meta-analysis was not conducted, and qualitative analysis showed that initial LD dose, LD dose per kilogram body weight, accumulated LD dose, and accumulated LD equivalent dose might be independent factors associated with motor complications. The time from disease onset to initiation of LD was not correlated with motor complications. DA as initial treatment was associated with later occurrence of dyskinesias (CALM-PD: HR = 0.37, 95% CI: 0.25 - 0.56, P < 0.001; PELMOPET: HR = 0.48, 95% CI = 0.29 - 0.80, P < 0.001; Ropinirole 056: HR = 0.4, 95% CI: 0.2 - 0.8, P = 0.007; REAL-PET: HR = 8.28, 95% CI: 2.46 - 27.93, P < 0.001). The relationship between LD treatment duration and motor complications could not be concluded from present evidence. Initial LD dose, LD dose per kilogram body weight, accumulated LD dose, and accumulated LD equivalent dose may be independent factors associated with motor complications. The time from disease onset to initiation of LD was not correlated with motor complications.