Highlights
- •Iron treatment is associated with a decrease in the restless legs syndrome score.
- •Oral and IV iron supplementation are a safe treatment with minor adverse effects.
- •Iron, oral or IV is effective therapy for patients with restless legs syndrome.
Abstract
Background
Iron supplementation, is recommended for the treatment of restless legs syndrome (RLS).
We gathered evidence for the efficacy and safety of iron supplementation for RLS.
Methods
A systematic review and meta-analysis of randomized controlled trials that compared
iron supplementation versus no iron for patients with RLS was performed. Multiple
databases were searched. The primary outcome was the effect of iron on the International
Restless Legs Syndrome score (IRLSS) at 4 weeks after treatment. For dichotomous data,
risk ratios (RR) with 95% confidence intervals (CIs) were estimated and pooled. For
continuous data, weighted mean differences (WMD) were calculated.
Results
Ten trials fulfilled the inclusion criteria. Iron therapy was associated with a significant
decrease of the IRLSS of −3.55 [95% CI (−5.41) – (−1.68)] points and an increase in
the percentage of patients with improvement of the IRLSS score, RR of 2.16 [95% CI
1.56–2.98]. IV FCM was associated with improvement in both the IRLSS (WMD of −2.79
(95% CI (−4.62) – (−0.96), 4 trials, I2 = 0%) and on the RLS-QOL by WMD of 8.67 (95% CI 1.68–15). Iron was associated with
an increased rate of adverse events RR 2.04 (95% CI 1.46–2.85), which were not severe
and not associated with increased rate of treatment discontinuation.
Conclusion
Iron supplementation is associated with improvement of the IRLSS score. Our meta-analysis
supports the use of iron, oral or IV, as effective therapy for patients with RLS.
Further studies should assess subgroups of patients most likely to benefit from iron
supplementation.
Keywords
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References
- Clinical practice. Restless legs syndrome.New Engl J Med. 2003; 348: 2103-2109
- Restless legs syndrome.Neurology. 1960; 10: 868-873
- Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: an IRLSSG task force report.Sleep Med. 2018; 41: 27-44
- Treatment of restless legs syndrome: evidence-based review and implications for clinical practice (Revised 2017) (section sign).Mov Disord. 2018; 33: 1077-1091
- Iron for restless legs syndrome.Cochrane Database Syst Rev. 2012; 5CD007834
- Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.PLoS Med. 2009; 6e1000097
- Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health.Sleep Med. 2003; 4: 101-119
- The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.BMJ. 2011; 343: d5928
Deng Y, Wu J, Jia Q. Efficacy of intravenous Iron sucrose in hemodialysis patients with restless legs syndrome (RLS): A randomized, placebo-controlled study. Medical Sci Monit, 2017;23:1254–60.
- A randomized, double-blind, placebo-controlled trial of intravenous iron sucrose in restless legs syndrome.Sleep Med. 2009; 10: 206-211
- Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial.Sleep Med. 2011; 12: 906-913
- Clinical efficacy of ferric carboxymaltose treatment in patients with restless legs syndrome.Sleep Med. 2016; 25: 16-23
- Efficacy of ferric carboxymaltose (FCM) 500 mg dose for the treatment of Restless Legs Syndrome.Sleep Med. 2018; 42: 7-12
- A randomized, double-blind, placebo controlled, multi-center study of intravenous iron sucrose and placebo in the treatment of restless legs syndrome.Mov Disord. 2009; 24: 1445-1452
- A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome.Am J Kidn Dis. 2004; 43: 663-670
- Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: a randomized trial.Mov Disord. 2017; 32: 1478-1482
- A randomized, double-blind placebo-controlled trial of iron in restless legs syndrome.Eur Neurol. 2000; 43: 70-75
- Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: a randomized, double-blind, placebo-controlled study.Sleep Med. 2009; 10: 973-975
- Review of quality of life instruments for the restless legs syndrome/Willis-Ekbom disease (RLS/WED): critique and recommendations.J Clin Sleep Med. 2014; 10: 1351-1357
- The safety of intravenous iron formulations: systematic review and meta-analysis.Mayo Clin Proc. 2015; 90: 12-23
- A double-blind, randomized, controlled trial to compare the efficacy and tolerability of fixed doses of ropinirole, bupropion, and iron in treatment of restless legs syndrome (Willis-Ekbom disease).Ann Ind Acad Neurol. 2016; 19: 472-477
- High incidence of iron depletion and restless leg syndrome (RLS) in regular blood donors: intravenous iron sucrose substitution more effective than oral iron.Vox Sang. 2010; 99: 354-361
Article info
Publication history
Published online: February 21, 2019
Accepted:
February 10,
2019
Received in revised form:
January 30,
2019
Received:
January 13,
2019
Identification
Copyright
© 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
