The presence of low iron in key areas of the brain has been implicated in the pathophysiology of RLS. Iron therapy, therefore, may be beneficial for treating RLS. Iron therapy can be either oral or intravenous. In a 12-week, randomized, double-blind trial of oral iron (ferrous sulphate, 325 mg/bid) versus placebo in patients with RLS who had ferritin levels between approximately 15 and 75 ng/mL, the oral iron treatment resulted in a significant improvement in RLS symptoms (P = .01).12 Thus, oral iron may be an important treatment option for patients with low or low-normal iron levels.
A number of studies have investigated intravenous iron for RLS. A recent study13 enrolled patients with moderate-to-severe RLS and low-to-normal iron levels; current RLS treatments were discontinued. The study found that the patients receiving treatment with a newer formulation of intravenous iron, ferric carboxymaltose, experienced significant improvement in RLS scores (P = .04), and 25% required no RLS medications at 24 weeks after the iron treatment. No significant adverse events were reported.
All patients with RLS should have their iron levels assessed using appropriate serum indicators such as ferritin levels, percentage of iron saturation, total iron-binding capacity, and early-morning fasting iron levels. Serum hemoglobin level is an insensitive indicator of iron deficiency. Low hemoglobin levels can indicate anemia, but an individual can be severely iron deficient for months or years before becoming anemic. Serum ferritin levels can be deceptive, too, because they increase with age, decreasing renal function, and inflammation.
Symptom improvement probably will not fully occur until 4 to 6 weeks after the iron infusion is given, so any decisions about the effectiveness of iron treatment or whether to discontinue other RLS treatments should not be made until this point. Clinicians should attempt to determine the serum ferritin level at which a patient’s RLS symptoms are most improved and then monitor the patient’s RLS symptoms over time, re-checking ferritin levels if symptoms worsen. Ferritin levels should be checked about 8 weeks after infusion, and 2 additional readings should be taken at 4-week intervals. In this way, the clinician can get an idea of whether the patient maintains a fairly stable iron status or loses iron rapidly. As long as the patient’s ferritin level is below 300 ng/mL, intravenous iron treatments can be repeated as needed to address symptoms. Based on clinical experience, a rough guide for determining an appropriate dose of intravenous iron is that every 100 mg of infused iron should increase the patient’s serum ferritin level by 10 to 12 ng/mL.