{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:22:27Z","timestamp":1792264947458,"version":"4.4.0"},"reference-count":49,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["\u201cRicerca Corrente\u201d (RC n. 2793745) to R. Ferri"],"award-info":[{"award-number":["\u201cRicerca Corrente\u201d (RC n. 2793745) to R. Ferri"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Neurol Disord"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>Restless legs syndrome (RLS) is a chronic sensorimotor disorder with a substantial impact on sleep, quality of life, and long-term neurological health. Because RLS has long required longitudinal clinical management in many patients, the major recent change is not the recognition of chronicity itself, but the reordering of treatment priorities as long-term evidence and clinical experience have clarified the risks of dopaminergic augmentation. This review synthesizes the progression of treatment paradigms from 2015 to 2026, focusing on how increasing recognition of augmentation has reshaped clinical decision-making. Historically, dopaminergic agents dominated RLS treatment because of robust short-term efficacy; however, their long-term risk-benefit profile has been reconsidered as augmentation became recognized as a major treatment-related complication. This led to a rebalancing of treatment strategies, with greater emphasis on iron metabolism and non-dopaminergic therapies. Iron deficiency is now considered a core pathophysiological and therapeutic target, with both oral and intravenous supplementation playing a key role even in the absence of overt anemia. Contemporary guidelines, culminating in the 2025 American Academy of Sleep Medicine recommendations, formalize this shift by endorsing \u03b12\u03b4 ligands (gabapentin, pregabalin, and gabapentin enacarbil) and intravenous iron as first-line treatments, while discouraging routine use of dopamine agonists due to long-term risks. The modern approach is therefore augmentation-aware, iron-conscious, and phenotype-oriented, incorporating structured pathways for refractory disease that may include opioids and emerging non-dopaminergic or device-based therapies. Despite these advances, however, important gaps remain, including limited evidence for augmentation management, lack of disease-specific pharmacotherapies, and insufficient data in special populations such as children and pregnant individuals. Future directions will likely depend on mechanism-based drug development, improved biomarkers, and precision medicine approaches. Overall, the evolution of RLS treatment reflects a broader transition toward sustainable, individualized care in chronic neurological disorders.<\/jats:p>","DOI":"10.1177\/17562864261469017","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:10:36Z","timestamp":1785240636000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["The evolving treatment landscape of restless legs syndrome"],"prefix":"10.1177","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6662-2281","authenticated-orcid":false,"given":"Maria P.","family":"Mogavero","sequence":"first","affiliation":[{"name":"Oasi Research Institute-IRCCS, Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5659-662X","authenticated-orcid":false,"given":"Giuseppe","family":"Lanza","sequence":"additional","affiliation":[{"name":"Clinical Neurophysiology Research Unit, Oasi Research Institute-IRCCS, Troina 94018, Italy"},{"name":"Department of Surgery and Medical-Surgical Specialties, University of Catania, Catania 95123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1202-8567","authenticated-orcid":false,"given":"Pasquale","family":"Tondo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy"},{"name":"Respiratory and Critical Care Unit, Department of Specialistic Medicine, University-Hospital Polyclinic of Foggia, Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2207-1398","authenticated-orcid":false,"given":"Oliviero","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6937-3065","authenticated-orcid":false,"given":"Raffaele","family":"Ferri","sequence":"additional","affiliation":[{"name":"Oasi Research Institute-IRCCS, Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00311-z"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2014.03.025"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2004.01.002"},{"key":"e_1_3_4_5_2","first-page":"4","article-title":"Restless legs syndrome","volume":"158","author":"Ekbom KA.","year":"1945","unstructured":"Ekbom KA. 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