Sleep Research Institute, Alberto Alcocer 19, Madrid, Spain.
Sleep Med Rev. 2010 Oct;14(5):339-46. doi: 10.1016/j.smrv.2009.11.006. Epub 2010 Mar 12.
Dopaminergic agents are the first-line treatment of restless legs syndrome (RLS), and have been used for the treatment of this disorder since the 1980s. The major issue with this class of drugs is augmentation of RLS symptoms during treatment. The first report of augmentation found an occurrence among 73% of patients treated with levodopa. Subsequent studies have reported somewhat lower incidences, but augmentation remains a clinically significant issue with all dopaminergic agents. It was not until 2007 that an operational, empirical definition of augmentation (Max Planck Institute Criteria) was made. This late development and the fact that studies have not been specifically designed to assess augmentation, have made it particularly difficult to compare the incidence rates for the different RLS treatments. As the primary neural and molecular substrates underlying idiopathic RLS are not known, the pathophysiology of augmentation remains unclear, however there are several hypotheses that concern the role of dopaminergic hyperstimulation, of iron deficiency, the genetic component, the effect of a reduction in responsiveness of tubero-infundibular dopamine receptors, and the role of chronobiotic mechanisms. RLS is treated by maintaining low doses of dopaminergic agents and ensuring iron sufficiency. Non-dopaminergics and opiates can be used when patients experience augmentation with more than one dopaminergic agent.
多巴胺能药物是治疗不安腿综合征（RLS）的一线药物，自 20 世纪 80 年代以来，一直用于治疗这种疾病。这类药物的主要问题是在治疗过程中会加剧 RLS 症状。首次报告发现，接受左旋多巴治疗的患者中有 73%出现了加剧现象。随后的研究报告称，发生率略低，但所有多巴胺能药物的加剧现象仍然是一个具有临床意义的问题。直到 2007 年，才提出了一种操作性的、经验性的加剧定义（马克斯·普朗克研究所标准）。这种后期发展，以及研究并未专门设计来评估加剧现象，使得比较不同 RLS 治疗方法的发生率变得特别困难。由于原发性 RLS 的主要神经和分子基础尚不清楚，因此加剧的病理生理学仍然不清楚，但是有几种假说涉及多巴胺能过度刺激、缺铁、遗传成分、结节漏斗多巴胺受体反应性降低的影响，以及chronobiotic 机制的作用。RLS 通过维持低剂量的多巴胺能药物和确保铁的充足来治疗。当患者出现一种以上多巴胺能药物加剧时，可以使用非多巴胺能药物和阿片类药物。
