Department of Neurology, University of Ioannina, Ioannina, Greece.
Eur J Neurol. 2014 Mar;21(3):433-40. doi: 10.1111/ene.12318. Epub 2013 Dec 7.
Dopamine agonists (DAs) are generally considered to be deprived of the highly dyskinetic effect of levodopa in Parkinson's disease (PD) patients. However, the risk for dyskinesia induced by DA monotherapy and the contribution of clinically significant factors in the development of this disorder have never been systematically assessed.
A systematic literature search was conducted for randomized, levodopa-controlled trials of DAs in early PD. A meta-analysis was performed to calculate the combined odds ratio (OR) for dyskinesia. Meta-regressions were subsequently performed on dyskinesia OR including individually as covariates the effects of mean disease duration, treatment duration and DA dose. In an additional analysis the effect of adjunct levodopa on the odds for dyskinesia was investigated.
DA monotherapy resulted in an 87% lower risk for dyskinesia compared with treatment with levodopa (OR = 0.13, 95% confidence interval 0.09-0.19, P < 0.001). The risk for dyskinesia was independent of the dose of DA, disease duration and treatment duration. A dose-related pattern was revealed between adjunct levodopa in the DA group and dyskinesia. Nevertheless, the odds for dyskinesia in the DA group were constantly lower than in the levodopa group.
Initial DA treatment encompasses a lower risk for dyskinesia even after the unavoidable introduction of levodopa that increases the risk for dyskinesia in a dose-related manner. As the dose and treatment duration with DAs are factors independent of the risk of dyskinesia, monotherapy with DAs in early PD is suggested at doses that ensure efficacy and delay the need for levodopa, always following an adequate evaluation of the risks DAs can pose in individual patients.
多巴胺激动剂（DA）通常被认为在帕金森病（PD）患者中缺乏左旋多巴的高度运动障碍作用。然而，DA 单药治疗引起运动障碍的风险以及导致这种疾病的临床显著因素的贡献从未被系统评估过。
对早期 PD 中 DA 的随机、左旋多巴对照试验进行了系统的文献检索。进行了荟萃分析以计算运动障碍的合并优势比（OR）。随后，对包括平均疾病持续时间、治疗持续时间和 DA 剂量作为协变量的运动障碍 OR 进行了荟萃回归。在另外的分析中，研究了附加左旋多巴对运动障碍几率的影响。
与左旋多巴治疗相比，DA 单药治疗导致运动障碍的风险降低了 87%（OR=0.13，95%置信区间 0.09-0.19，P<0.001）。运动障碍的风险与 DA 的剂量、疾病持续时间和治疗持续时间无关。在 DA 组中附加左旋多巴与运动障碍之间显示出剂量相关的模式。然而，DA 组运动障碍的几率始终低于左旋多巴组。
即使在不可避免地引入左旋多巴后，初始 DA 治疗也包含较低的运动障碍风险，因为左旋多巴以剂量相关的方式增加了运动障碍的风险。由于 DA 的剂量和治疗持续时间是独立于运动障碍风险的因素，因此建议在早期 PD 中使用 DA 进行单药治疗，剂量应确保疗效并延迟对左旋多巴的需求，始终在对 DA 对个体患者可能造成的风险进行充分评估的基础上进行。
