Efficacy and safety of iron supplements for restless leg syndrome, a systematic review, meta-analysis, meta-regression, and trial sequential analysis of randomized controlled trials.

Background: Restless leg syndrome (RLS) is a common neurological condition that can affect the quality of life. Iron is one of the available options for the treatment of RLS.

Methods: This systematic review and meta-analysis assessed the efficacy and safety of different iron regimens in treating RLS. We searched EMBASE, SCOPUS, Web of Science, PubMed, and Cochrane databases for studies that assessed the effects of different iron supplements compared to placebo on the International RLS score (IRLS), RLS-Quality of Life (QOL) score, sleep visual analog score (VAS), and adverse events (AEs).

Results: Twelve randomized controlled trials with 511 patients were included. Iron improved the IRLS score (mean difference [MD] = -5.28; 95% confidence interval [CI] - 7.66, -2.90; P < 0.0001), the number of patients with improved IRLS score (risk ratio [RR] = 2.06; 95% CI 1.49, 2.84; P < 0.0001), RLS-QOL (MD = 7.42; 95% CI 1.32, 13.51; P = 0.02), and sleep VAS score (MD = -24.83; 95% CI -40.08, -9.58; P = 0.001), but yielded more overall AEs (RR = 2.04; 95% CI 1.46, 2.85; P < 0.0001), with no difference in serious AEs or those leading to drug discontinuation (RR = 2.04; 95% CI 0.39, 10.81; P = 0.40 and RR = 6.25; 95% CI 0.79, 49.54; P = 0.08), respectively.

Conclusion: Iron, especially ferric carboxymaltose, is a valuable option for RLS, which showed improvement in several indices.