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Iron supplementation for restless legs syndrome – A systematic review and meta-analysis

  • Author Footnotes
    1 Equal contribution.
    Tomer Avni
    Correspondence
    Corresponding author at: Department of Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva 49100, Israel.
    Footnotes
    1 Equal contribution.
    Affiliations
    Internal Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel and Sackler Faculty of Medicine, Tel-Aviv University, Israel
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  • Author Footnotes
    1 Equal contribution.
    Shelley Reich
    Footnotes
    1 Equal contribution.
    Affiliations
    Internal Medicine A, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel and Sackler faculty of Medicine, Tel-Aviv University, Israel
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  • Nirit Lev
    Affiliations
    Neurology Department, Meir Medical Center, Kfar Saba, Israel and Sackler Faculty of Medicine, Tel-Aviv University, Israel
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  • Anat Gafter-Gvili
    Affiliations
    Internal Medicine A, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel and Sackler faculty of Medicine, Tel-Aviv University, Israel
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  • Author Footnotes
    1 Equal contribution.
Published:February 21, 2019DOI:https://doi.org/10.1016/j.ejim.2019.02.009

      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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