Efficacy of Iron Treatment for Restless Legs Syndrome

Although there are substantial data implicating a primary role for iron insufficiency in restless legs syndrome (RLS) (see Chapter 10), the actual effectiveness of iron treatment in RLS has been underexplored and relatively limited in its scientific assessment. The routes of administration available for iron therapy are oral, intravenous, and intramuscular. Oral and intravenous treatments have been studied in RLS. Oral iron treatment has all the limitations associated with a gut-blood-barrier physiology (see Chapter 9). There is high absorption (20% to 30%) of iron under severe iron deficient conditions (ferritin <5 μg/L), but absorption drops exponentially with increasing body iron stores: absorption of about 2% with ferritin of 60 to 80 μg/L and absorption of about 1% with ferritin above 100 μg/L. Those studies that have reported a benefit of oral iron treatment in RLS have been open-label design, and patients with low or deficient iron stores had been treated.^1,2 There is one randomized, double-blind study of oral iron therapy in RLS.³ In this study, patients received either 130 mg of iron per day or placebo over a 12- to 14-week period. The average baseline serum ferritin levels were about 150 μg/L. Iron treatment showed no benefits and, not surprisingly, the average ferritin did not change. Therefore, the study did not prove that iron was ineffective as a treatment for RLS, only that the route of administration was ineffective in raising the body iron stores.

The limitation imposed by the gut’s restriction on iron absorption can be bypassed by giving iron intravenously. Nordlander⁴ was the first to demonstrate that multiple, small intravenous doses of iron could bring about marked improvements in RLS symptoms. The range of the total cumulative doses of iron given was approximately 300 to 1000 mg. Twenty-one of 22 patients reported substantial improvements of symptoms. These patients were not anemic before treatment. In another open-label study, 10 nonanemic subjects with idiopathic RLS each received a single, 1000-mg infusion of iron dextran. Seven of 10 subjects reported improvements with 6 of 10 reporting a complete resolution of symptoms.⁵ Not only did symptoms improve, but also the periodic limb movement rates dropped significantly from baseline values following treatment.

Despite the initial improvements in symptoms, the majority of patients in both studies had, on average, a return of symptoms within 5 to 6 months. Nordlander⁴ reports giving supplemental intravenous iron treatments to some of those whose symptoms returned, but the outcome of supplemental treatment was not reported. In the study by Earley and colleagues,⁵