Iron therapy & restless legs syndrome: a narrative review.

introductionRestless legs syndrome (RLS) is a prevalent sensorimotor disorder with a well-established pathophysiological link to brain iron deficiency. While iron supplementation is a cornerstone of management, optimal therapeutic strategies regarding formulation, dosing, and patient selection remain subjects of ongoing research. This narrative review evaluates the current evidence on the efficacy and safety of iron therapy, specifically intravenous (IV) ferric carboxymaltose (FCM) and oral iron, in the management of RLS.

methodsA targeted literature search was conducted using PubMed, Google Scholar, and the Cochrane Library databases to identify relevant studies published from January 2015 to July 2025. The search prioritized randomized controlled trials (RCTs), systematic reviews, and large observational studies. Seventeen key publications were selected for synthesis, focusing on clinical outcomes, safety profiles, and predictive biomarkers for treatment response.

resultsEvidence consistently demonstrates that IV FCM, particularly at a total dose of ≥ 1000 mg, significantly reduces International Restless Legs Syndrome Study Group (IRLS) scores and improves quality of life in patients with moderate-to-severe RLS or those intolerant to oral iron. Oral iron remains a viable first-line option for children and mild cases, although efficacy varies due to absorption limitations. Subgroup analyses indicate benefits in pregnant women, dialysis patients, and the elderly. Adverse events with IV iron were generally mild (e.g., transient hypophosphatemia). Notably, a transferrin saturation (TSAT) ≤ 35% was identified as a more sensitive predictor of favorable treatment response than serum ferritin alone.

conclusionIron supplementation, particularly via IV FCM, is a safe and effective disease-modifying treatment for RLS. Clinicians should prioritize a personalized approach, utilizing TSAT and ferritin to guide patient selection. Future research is needed to standardize repeated dosing protocols and investigate long-term safety in non-anemic populations.