A randomized, double‐blind, placebo controlled, multi‐center study of intravenous iron sucrose and placebo in the treatment of restless legs syndrome

Abstract

Iron deficiency may exacerbate symptoms in the Restless Legs Syndrome (RLS). We investigated the effect of intravenous iron sucrose or placebo on symptoms in patients with RLS and mild to moderate iron deficit. Sixty patients with primary RLS (seven males, age 46 (9) years, S-ferritin < or =45 microg/L) recruited from a cohort of 231 patients were randomly assigned in a 12-months double-blind, multi-centre study of iron sucrose 1000 mg (n = 29) or saline (n = 31). The primary efficacy variable was the RLS severity scale (IRLS) score at week 11. Median IRLS score decreased from 24 to 7 (week 11) after iron sucrose and from 26 to 17 after placebo (P = 0.123, N.S. for between treatment comparison). The corresponding scores at week 7 were 12 and 20 in the two groups (P = 0.017). Drop out rate because of lack of efficacy at 12 months was 19/31 after placebo and 5/29 patients after iron sucrose (Kaplan-Meier estimate, log rank test P = 0.0006) suggesting an iron induced superior long term RLS symptom control. Iron sucrose was well tolerated. This study showed a lack of superiority of iron sucrose at 11 weeks but found evidence that iron sucrose reduced RLS symptoms both in the acute phase (7 weeks) and during long-term follow up in patients with variable degree of iron deficiency. Further studies on target patient groups, dosing and dosing intervals are warranted before iron sucrose could be considered for treatment of iron deficient patients with RLS.

Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial

“…17 However, the effect size for quality of life appears to be smaller than for fatigue alone; thus, our study was underpowered to reveal a significant effect. Positive effects on physical and psychological performances can be explained by the known effects of iron, which include improving aerobic adaptation, endurance capacity, 15,18,19 muscle fatigability, 20,21 restless leg syndrome, 22 memory, verbal learning and cognitive function. [23][24][25] The effects of iron deficiency on fatigue can be explained by decreased activity of irondependent enzymes; for example, those affecting the metabolism of neurotransmitters that enhance neurophysiologic changes.…”

Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: A randomized trial

“…Unlike other treatments, which may be administered several times over the trial period,6, 8 FCM was administered as a single intravenous dose. This may have increased the likelihood of withdrawal if patients were administered placebo treatment or possibly had a noniron‐sensitive RLS phenotype and could not tolerate RLS symptoms over time.…”

“…Compromised iron status is an important disorder, possibly contributing to the cause of RLS 3. However, the causal relationship still remains unclear, and there is much debate about how to adequately assess iron status in RLS patients 4, 5, 6, 7, 8. The potential relationship between low iron status and RLS has led to increased interest in the use of iron replacement therapy to treat this disorder 1.…”

“…Study results have varied, most likely because of the different iron formulations and dosages used, as well as study design. Although some previous studies excluded anemic patients,7 all studies to date have included patients of varied iron status, but have not provided clear evidence about which RLS patients might benefit most from iron treatment 6, 7, 8, 9, 10, 11…”

Brazilian consensus on guidelines for diagnosis and treatment for restless legs syndrome

“…The systematic review allowed the identification of two studies using the primary route iron 84,85 and four primary studies that used intravenous iron 86,87,88,89 . The use of iron led to a reduction of 3.8 points in RLS Severity Scale, and dopaminergic agonists reduce an average of 5.7 points.…”