Restless legs syndrome (RLS) is a common medical condition that results in uncomfortable urges to move the legs, especially in the evening and at night, and often interferes with sleep. Low blood levels of iron are frequently seen in people who have RLS and the lack of iron may be part of the cause of RLS. Iron can be supplemented either in pill form or through injections into the bloodstream. This review was performed to see if iron supplements are effective in reducing the symptoms of RLS. Six studies of iron were included, which together involved only 192 subjects. Results from the studies were conflicting, with some studies showing that iron was not effective but others showing some help for patients' feelings of restlessness or discomfort. Because of the different ways in which the studies were done, we could not combine results from all of the studies to come up with an overall judgement of whether or not iron is effective. Two of the studies were limited to specific sub-groups of RLS patients, who might be expected to respond to iron differently than would the RLS group as a whole. The study of RLS patients with severe kidney disease showed a benefit of iron therapy. The study of RLS patients with low blood levels of iron did not consistently show a benefit of iron therapy at all time points. Iron did not cause any more side effects than the placebo medication. More studies are needed before we will be able to determine whether iron therapy should be used for patients with RLS.
There is insufficient evidence to determine whether iron therapy is beneficial for the treatment of RLS. Further research to determine whether some or all types of RLS patients may benefit from iron therapy, as well as the best route of iron administration, is needed.
Restless legs syndrome (RLS) is a common neurologic syndrome and is associated with iron deficiency in many patients. It is unclear whether iron therapy is effective treatment for RLS.
The objective of this review was to assess the effects of iron supplementation (oral or intravenous) for patients with RLS.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Jan 1995 to April 2011); EMBASE (Jan 1995 to April 2011); PsycINFO (Jan 1995 to April 2011); and CINAHL (Jan 1995 to April 2011). Corresponding authors of included trials and additional members of the International Restless Legs Syndrome Study Group were contacted to locate additional published or unpublished trials.
Controlled trials comparing any formulation of iron with placebo, other medications, or no treatment in adults diagnosed with RLS according to expert clinical interview or explicit diagnostic criteria.
Two review authors extracted data and at least two authors assessed trial quality. We contacted trial authors for missing data.
Six studies (192 total subjects) were identified and included in this analysis. The quality of trials was variable. Our primary outcome was restlessness or uncomfortable leg sensations, which was quantified using the IRLS severity scale in four trials and another RLS symptom scale in a fifth trial. Combining data from the four trials using the IRLS severity scale, there was no clear benefit from iron therapy (mean difference in IRLS severity scores of -3.79, 95% CI: -7.68 to 0.10, p = 0.06). However, the fifth trial did find iron therapy to be beneficial (median decrease of 3 points in the iron group and no change in the placebo group on a 10 point scale of RLS symptoms, p = 0.01). Quality of life was improved in the iron group relative to placebo in some studies but not others. Changes in periodic limb movements were not different between groups (measured in two studies). Objective sleep quality, subjective sleep quality and daytime functioning were not different between treatment groups in the studies that assessed them. The single study of subjects with end stage renal disease did show a benefit of therapy. Most trials did not require subjects to have co-morbid iron deficiency and several excluded patients with severe anemia. The single study that was limited to iron deficient subjects did not show clear benefit of iron supplementation on RLS symptoms. There was no clear superiority of oral or intravenous delivery of iron. Iron therapy did not result in significantly more side effects than placebo (RR 1.39, 95% CI 0.85 to 2.27).