Sleep Disorders Center, Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.
Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.
Sleep Med. 2023 Dec;112:173-180. doi: 10.1016/j.sleep.2023.10.022. Epub 2023 Oct 20.
Augmentation of restless legs syndrome (RLS) is an iatrogenic side effect induced by dopaminergic agents, and it is a major cause of therapeutic failure. Iron deficiency is a risk factor for RLS, but its effects on the development of RLS augmentation are unclear. This meta-analysis aimed to elucidate the association between serum ferritin and RLS augmentation.
We searched the PubMed, Cochrane Library, Embase, ClinicalKey, ScienceDirect, and ProQuest databases for studies comparing the serum ferritin levels of patients with augmented RLS and nonaugmented RLS. A meta-analysis based on a random-effects model was conducted. Levodopa equivalent dose (LED), International Restless Legs Study Group Severity Rating Scale (IRLS), and serum hemoglobin levels were also analyzed.
Six observational studies fulfilled the eligibility criteria of this meta-analysis. A total of 220 RLS patients with augmentation and 687 RLS patients without augmentation were included. The results revealed that augmented RLS was significantly associated with low serum ferritin levels (p = 0.002), high LEDs (p = 0.026), and nonsignificantly associated with high IRLS scores (p = 0.227).
A low serum ferritin level is associated with RLS augmentation. For patients with RLS who are iron deficient, iron supplements can not only relieve their fundamental RLS symptoms but also lower the risk of RLS augmentation. Moreover, non-dopminergic agents should be considered as the first-line treatment for patients with persistent low serum ferritin levels or those with moderate to severe RLS to prevent augmentation.
不宁腿综合征（RLS）的加重是多巴胺能药物引起的医源性副作用，是治疗失败的主要原因。缺铁是 RLS 的一个危险因素，但它对 RLS 加重的影响尚不清楚。本荟萃分析旨在阐明血清铁蛋白与 RLS 加重之间的关系。
我们检索了 PubMed、Cochrane 图书馆、Embase、ClinicalKey、ScienceDirect 和 ProQuest 数据库，以比较加重和非加重 RLS 患者的血清铁蛋白水平。采用随机效应模型进行荟萃分析。还分析了左旋多巴等效剂量（LED）、国际不宁腿研究组严重程度评分量表（IRLS）和血清血红蛋白水平。
六项观察性研究符合本荟萃分析的纳入标准。共有 220 例伴有 RLS 加重的 RLS 患者和 687 例无 RLS 加重的 RLS 患者被纳入。结果表明，RLS 加重与血清铁蛋白水平低（p=0.002）、LED 高（p=0.026）显著相关，与 IRLS 评分高（p=0.227）无显著相关。
血清铁蛋白水平低与 RLS 加重有关。对于患有 RLS 且缺铁的患者，铁补充剂不仅可以缓解其根本的 RLS 症状，还可以降低 RLS 加重的风险。此外，对于持续低血清铁蛋白水平或中重度 RLS 的患者，应考虑使用非多巴胺能药物作为一线治疗，以预防加重。
