Comparison 1. Iron versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in IRLS severity scale score	7	345	Mean Difference (IV, Random, 95% CI)	‐3.78 [‐6.25, ‐1.31]
2 Change in any measure of restlessness	8	370	Std. Mean Difference (IV, Random, 95% CI)	‐0.74 [‐1.26, ‐0.23]
2.1 New Subgroup	8	370	Std. Mean Difference (IV, Random, 95% CI)	‐0.74 [‐1.26, ‐0.23]
3 Restlessness, Subgroup ‐ renal disease	8	370	Std. Mean Difference (IV, Random, 95% CI)	‐0.74 [‐1.26, ‐0.23]
3.1 Normal renal function	6	313	Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.57, ‐0.04]
3.2 Renal disease requiring dialysis	2	57	Std. Mean Difference (IV, Random, 95% CI)	‐2.18 [‐3.31, ‐1.06]
4 Restlessness, Subgroup ‐ iron status at baseline	8	370	Std. Mean Difference (IV, Random, 95% CI)	‐0.74 [‐1.26, ‐0.23]
4.1 Low or low‐normal baseline iron stores	3	188	Std. Mean Difference (IV, Random, 95% CI)	‐0.37 [‐0.81, 0.07]
4.2 Unselected for baseline iron measures	5	182	Std. Mean Difference (IV, Random, 95% CI)	‐0.95 [‐1.85, ‐0.06]
5 Restlessness, Subgroup ‐ intravenous versus oral iron	8	370	Std. Mean Difference (IV, Random, 95% CI)	‐0.74 [‐1.26, ‐0.23]
5.1 Oral iron	1	18	Std. Mean Difference (IV, Random, 95% CI)	‐1.29 [‐2.35, ‐0.23]
5.2 Intravenous iron	7	352	Std. Mean Difference (IV, Random, 95% CI)	‐0.68 [‐1.23, ‐0.14]
6 Restlessness, Subgroup ‐ iron sucrose versus ferric carboxymaltose	6	327	Std. Mean Difference (IV, Random, 95% CI)	‐0.55 [‐1.09, 0.00]
6.1 Iron sucrose	3	110	Std. Mean Difference (IV, Random, 95% CI)	‐0.88 [‐2.48, 0.72]
6.2 Ferric carboxymaltose	3	217	Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.57, ‐0.04]
7 Restlessness, Sensitivity analysis ‐ excluding studies at high risk of bias	7	338	Std. Mean Difference (IV, Random, 95% CI)	‐0.46 [‐0.82, ‐0.10]
8 Quality of life (dichotomous measure)	2	39	Risk Ratio (M‐H, Random, 95% CI)	2.01 [0.54, 7.45]
9 Change in quality of life (continuous measure)	3	128	Std. Mean Difference (IV, Random, 95% CI)	0.51 [0.15, 0.87]
10 Withdrew to use other RLS medication or because of inadequate RLS symptom control	9	391	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.41, 1.47]
11 Change in subjective sleep quality	3	128	Std. Mean Difference (IV, Random, 95% CI)	0.19 [‐0.18, 0.56]
12 Change in PLMS	2	60	Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.70, 0.32]
13 Adverse events	6	298	Risk Ratio (M‐H, Random, 95% CI)	1.48 [0.97, 2.25]
14 Gastrointestinal side effects	8	380	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.76, 2.75]
15 Drop out due to adverse event	9	398	Risk Ratio (M‐H, Random, 95% CI)	1.91 [0.50, 7.26]