Traditional Chinese Medicine Herbal Preparations in Restless Legs Syndrome (RLS) Treatment: a Review and Probable First Description of RLS in 1529

Occidental medicine has a given definition for restless legs syndrome (RLS) and knowledge of RLS pathophysiology has led to the development of its therapeutic management. RLS has no cure. Many methods have been used for its treatment, among which traditional Chinese medicine (TCM) has been considered as a new approach. However, description and management of the disease symptoms can be found in Chinese ancient medical systems. The first mention of RLS may have been as early as the third century BC described as "leg uncomfortable". Nonetheless, the lack of a complete description encompassing all four modern cardinal features of RLS makes this uncertain. On the other hand, the first description of RLS encompassing three of the four major modern criteria occurs in the ancient book of Neike Zhaiyao (Internal summary), 1529 AD just about a century and a half prior to the description of RLS by Sir Thomas Willis in England. Here, we introduce the philosophical concepts of traditional Chinese medicine and the description, classification and understanding of RLS symptoms in traditional Chinese medicine. We have conducted an in-depth review of the literature reporting one part of TCM, Chinese herbal treatment efficacy for RLS, through both English and Chinese search engines. Eighty-five studies were included in the review and more than 40 formulas (including 176 different ingredients) were found in the literature. According to the literature, Chinese herbs have been demonstrated to be safe and hold great potential to be an effective treatment modality for RLS, but the evidence is limited by the quality of these studies. Of the eighty-five studies, only nine were clinical trials with a control group and only three of them were randomized. In cases where herbal preparations were compared to Western medications for RLS, the herbal preparations appear to be superior. However, uncertainty as to whether the diagnosis of RLS was made in accord with Western norms and the use of homemade non-validated rating scales create uncertainty as to the meaning of these results. High-quality randomized and double blinded clinical trials of Chinese herbs in treating RLS will be required in the future. This review highlights aspects of Chinese herbal treatment important to guide future research and clinical practice. To our knowledge, this is the first systematic English review of the role of Chinese herbs in the treatment of RLS.