Duration of Iron Supplementation for Restless Legs Syndrome
Iron therapy for RLS should be continued indefinitely with ongoing monitoring, as the 2025 American Academy of Sleep Medicine guidelines do not specify a fixed treatment duration, and the evidence shows that RLS symptoms may recur if iron stores decline below therapeutic thresholds. 1
Initial Treatment Period and Response Assessment
Begin iron supplementation when ferritin ≤75 ng/mL or transferrin saturation <20%, using either oral ferrous sulfate (65 mg elemental iron daily) or IV ferric carboxymaltose (1000 mg single dose). 2, 3
Reassess RLS symptoms and iron parameters at 12-16 weeks after initiating oral iron therapy, as most clinical trials evaluated outcomes at 2-12 weeks post-treatment. 4, 5
For IV iron formulations (ferric carboxymaltose, ferumoxytol, or low molecular weight iron dextran), symptom improvement typically occurs within 2-12 weeks, with response assessment recommended at 7-12 months. 6
Long-Term Monitoring Strategy
Recheck serum ferritin and transferrin saturation every 6-12 months during ongoing iron therapy to ensure maintenance of therapeutic iron levels and avoid iron overload. 7
Continue iron supplementation as long as ferritin remains ≤75 ng/mL or transferrin saturation <20%, as these are the RLS-specific thresholds (not general population cutoffs of <15-30 ng/mL). 2, 3
If hemoglobin rises significantly above normal during treatment, temporarily discontinue iron and evaluate for other causes of polycythemia before resuming. 8
Treatment Duration Based on Response
For responders (76% of patients in case series): Continue iron therapy indefinitely with biannual monitoring, as RLS symptoms may recur if iron stores decline. 6
For non-responders after 12-16 weeks: Verify adequate iron repletion (hemoglobin >12.5 g/dL in women, >13.5 g/dL in men) before concluding treatment failure, as inadequate dosing may explain lack of response. 6
Consider higher IV iron doses (>1000 mg) or repeat dosing if initial treatment fails to normalize hemoglobin, particularly in patients with persistent RLS despite "adequate" ferritin levels. 6
Critical Monitoring Points
Screen for hemochromatosis before initiating iron therapy by measuring baseline transferrin saturation and ferritin; if transferrin saturation >45% or ferritin >300 ng/mL in men or >200 ng/mL in women, evaluate for iron overload disorders including HFE gene mutations. 7
Monitor for common side effects of oral iron (constipation, gastrointestinal upset) that may limit long-term adherence, particularly in pediatric patients. 1, 8
Avoid checking iron studies while patients are taking supplements; wait at least 24 hours after the last iron-containing product and test in the morning for accurate assessment. 2, 8
Special Populations
End-stage renal disease patients: Use IV iron sucrose with ferritin target <200 ng/mL and transferrin saturation <20%, with ongoing monitoring coordinated with dialysis schedules. 2
Pediatric RLS: Continue oral iron supplementation as long as ferritin remains <50 ng/mL, with careful monitoring for constipation and other side effects. 2, 3
Pregnancy: Iron supplementation is particularly important given pregnancy-specific RLS prevalence, with safety profile favoring oral formulations throughout gestation. 1
When to Discontinue Iron Therapy
Consider discontinuation only if ferritin consistently remains >100 ng/mL on repeat testing and RLS symptoms have completely resolved for at least 6 months. 3
Even with symptom resolution, maintain surveillance with iron studies every 6-12 months, as brain iron deficiency may persist despite normal serum parameters. 1
If symptoms recur after discontinuation, resume iron supplementation immediately and reassess iron parameters. 6