Symptom Improvement After Iron Infusion for Restless Legs Syndrome
Most patients with iron-deficiency-related restless legs syndrome begin experiencing symptom improvement within 1 week after a single intravenous iron infusion, with clinically meaningful effects typically evident by day 8. 1
Timeline of Response
Early response (1 week): A prospective observational study of 500 mg ferric carboxymaltose demonstrated that responders showed clinically relevant improvement in RLS severity as early as day 8 after infusion. 1
Peak response (3 weeks): In the same study, the International RLS Severity Scale (IRLS) score decreased from 28.3 to 18.3 in responders by 3 weeks post-infusion, representing a clinically significant reduction. 1
Duration of benefit: The effect of a single 1000 mg iron infusion typically lasts approximately 6 months (range 1–60 weeks) before symptoms return and repeat dosing may be needed. 2, 3
Factors Predicting Response
Younger patients tend to respond better to IV iron therapy. 1
Lower baseline ferritin levels (particularly <45 μg/L) are associated with better response rates. 1
Fewer comorbid conditions predict a more favorable response to IV iron treatment. 1
Approximately 76% of patients with RLS and iron deficiency anemia respond to a single 1000 mg infusion, with 47% maintaining improvement beyond 6 months. 4
Guideline-Recommended Approach
The American Academy of Sleep Medicine strongly recommends IV ferric carboxymaltose (750–1000 mg in one or two infusions) for adults with RLS when ferritin ≤75 ng/mL or transferrin saturation <20%. 5, 6
Iron status should be assessed with morning fasting ferritin and transferrin saturation after withholding iron supplements for ≥24 hours before treatment. 5, 6
IV iron is particularly valuable for patients with severe RLS symptoms and iron deficiency, as it can avoid or postpone the need to change or uptitrate RLS-specific medications due to the rapid response. 1
Formulation Considerations
Ferric carboxymaltose allows delivery of up to 1000 mg in a single 15-minute infusion without requiring a test dose. 5, 7
Low-molecular-weight iron dextran can deliver 1000 mg as a single dose but requires a test dose and longer infusion time (4–6 hours). 5
Iron sucrose requires multiple smaller doses (200 mg per injection) and has shown less consistent efficacy in RLS compared to higher-dose, slow-release formulations. 5
Common Pitfalls to Avoid
Do not wait for ferritin to normalize before expecting symptom improvement—clinical response can occur within 1 week even though ferritin levels continue to rise over subsequent weeks. 1
Do not assume non-response after only 3–4 days—allow at least 1–2 weeks to assess efficacy before concluding treatment failure. 1
Do not rely solely on ferritin levels to predict response—some patients with ferritin 75–100 ng/mL may still benefit from IV iron, as brain iron deficiency can persist despite normal serum parameters. 5, 6
Monitor for symptom recurrence at 6-month intervals, as the effect of a single infusion typically wanes after approximately 6 months and repeat dosing may be needed. 2
Ensure adequate iron repletion—non-responders often have below-normal hemoglobin levels (<12.5 g/dL), suggesting inadequate treatment of iron deficiency; some patients may require doses higher than the standard 1000 mg. 4