Date Published: 
Thursday, 4 September, 2014

Iron therapy for restless leg syndrome

Professor Michael Auerbach

Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is characterised by largely nocturnal, rest-induced, distressing urges to move the legs1.  Insomnia, interference with relationships and cramps are common, contributing to a decreased quality of life2,3. Iron deficiency is commonly associated with RLS2,3 and there are approximately three million patients in the USA alone with both conditions4. The role of intravenous iron as a primary therapy for iron deficient patients with RLS has become an area of major clinical research5

In 2013, the Auerbach Hematology-Oncology practice (Maryland, USA) began administering the 13-item sleep-vitality questionnaire and the 13-item Cambridge Hopkins RLS diagnostic questionnaire to patients diagnosed with anaemia2.  These scales evaluate tiredness, weakness, energy levels, and various aspects of sleep. A four- to five-fold increase in incidence of RLS was observed in the iron deficient population. In addition, this patient group produced a much greater disruption of sleep and shorter sleep times. The data highlighted the need for identification of RLS in patients with iron deficiency and consideration of appropriate therapeutic interventions.

Current treatment of RLS is suboptimal. Medications such as pregabalin and pramepexole are widely used but are associated with fatigue. Oral iron therapy may provide clinical benefit to iron deficient patients with RLS but has several limitations, including patient intolerance6,7. A single infusion of intravenous iron may provide substantial therapeutic advantages5.  At our practice, the administration of total-dose infusion of intravenous iron has shown immediate clinical benefit for many patients.

The role of total-dose infusion of intravenous iron is considered controversial. Published evidence indicates unacceptable toxicity and serious adverse events8. However, the majority of research has been conducted with high molecular weight iron dextran, which has now been removed from the market due to safety concerns. At our practice, no serious adverse events were observed in a series of 1,266 infusions of low molecular weight iron dextran (1000 mg in one hour) in 888 patients with iron deficiency many of whom suffered from RLS. Furthermore, several recent studies have reported improvement of RLS symptoms in patients administered low molecular weight iron dextran without any significant adverse events9,10.  

Further randomised, placebo controlled studies comparing oral iron to intravenous iron in RLS are required. It is likely that infusions of large doses of intravenous iron in a single setting will offer a considerable improvement over other forms of therapy for RLS in the future.  Several intravenous iron formulations have recently become available which may offer complete replacement dosing in fifteen minutes or less11–13. Considering the prevalence of iron deficiency anaemia and RLS, and their significant impact on quality of life, iron therapy infusions may be of substantial clinical value to this patient group.