Iron for Restless Legs Syndrome

Summary

A Cochrane review [Abstract] 1 included 10 studies with a total of 428 subjects with restless legs syndrome (RLS). The primary outcome was restlessness or uncomfortable leg sensations, which was quantified using the International Restless Legs Scale (IRLS) (range 0 to 40) in 8 trials and a different RLS symptom scale in one trial. Nine studies compared iron to placebo and one study to a dopamine agonist (pramipexole). The follow-up times varied from 2 to 14 weeks. Use of iron resulted in greater improvement in IRLS scores (MD 3.78, 95% CI -6.25 to -1.31; 7 studies, n=345) measured 2 to 12 weeks after treatment. In the eighth study, using a different scale, use of iron remained beneficial vs. placebo (SMD -0.74, 95% CI -1.26 to -0.23; 8 studies, n=370). One study comparing iron to a dopamine agonist (pramipexole) found a similar reduction in RLS severity in both groups (MD -0.40, 95% CI -5.93 to 5.13; n=30). Iron did not improve quality of life as a dichotomous measure (RR 2.01, 95% CI 0.54 to 7.45; 2 studies, n=39), but did improve quality of life measured on continuous scales (SMD 0.51, 95% CI 0.15 to 0.87; 3 studies, n=128) vs. placebo. Subjective sleep quality was not different between iron and placebo groups (SMD 0.19, 95% CI -0.18 to 0.56; 3 studies, n=128), nor was objective sleep quality, as measured by change in sleep efficiency in a single study (-35.5 +/- 92.0 vs. -41.4 +/- 98.2; n=18). Periodic limb movements of sleep were not significantly reduced with iron vs. placebo (SMD -0.19, 95% CI -0.70 to 0.32; 2 studies, n=60). Iron did not improve sleepiness vs. placebo, as measured on the Epworth Sleepiness Scale (1 study, n=60) but did improve the daytime tiredness item of the RLS-6 vs. placebo (least squares MD -1.5, 95% CI -2.5 to -0.6; 1 study, n=110). The use of low serum ferritin levels as an inclusion criteria and the use of oral vs. iv. iron did not show significant subgroup differences.

Comment: The quality of the evidence is downgraded by inconsistency (heterogeneity in treatments) and indirectness (short follow-up times).