How to treat Restless Legs Syndrome (RLS) with iron supplementation?

From the Guidelines

Iron supplementation is a strongly recommended treatment for Restless Legs Syndrome (RLS), particularly when associated with iron deficiency, with IV ferric carboxymaltose receiving a strong recommendation for adults 1.

Treatment Approach

For adults with RLS, the following approach is suggested:

• Routine screening of iron indices is essential, and supplementation indices are different for people with RLS than the general adult population.
• IV ferric carboxymaltose is recommended for adults with RLS, given its strong evidence base and ability to improve symptoms 1.
• Oral iron supplementation with ferrous sulfate is suggested with a conditional recommendation based on limited RCT data, and it may be considered for those who cannot tolerate or do not have access to IV iron formulations 1.
• When using oral iron, ferrous sulfate 325 mg taken twice daily on an empty stomach with vitamin C 100 mg to enhance absorption is a reasonable regimen, which should continue for 3 months, after which ferritin levels should be rechecked 1.

Important Considerations

• Iron supplementation works because RLS is often linked to insufficient iron in the brain, which affects dopamine production and function - key factors in RLS symptoms.
• For better absorption, iron supplements should be taken separately from calcium-containing foods, coffee, tea, and certain medications.
• Side effects may include constipation, nausea, and black stools, and patients should be monitored for these adverse effects.
• Patients should have their iron status (ferritin, transferrin saturation) checked before starting supplementation, and those with hemochromatosis or iron overload conditions should avoid iron supplements.
• Improvement in RLS symptoms may take several weeks to become noticeable as brain iron stores gradually replenish.

Key Points to Remember

• Iron supplementation is a key component of RLS treatment, particularly when associated with iron deficiency.
• IV ferric carboxymaltose is a strongly recommended treatment option for adults with RLS.
• Oral iron supplementation may be considered for those who cannot tolerate or do not have access to IV iron formulations.
• Regular monitoring of iron status and adjustment of supplementation regimens as needed is crucial to optimize treatment outcomes.

From the Research

Iron Supplementation for Restless Legs Syndrome

• Iron supplementation is recommended for the treatment of restless legs syndrome (RLS), particularly for patients with low normal serum indexes 2, 3, 4.
• The efficacy of iron therapy for RLS is supported by some studies, which found a significant decrease in RLS symptoms and improvement in quality of life 3, 4.
• However, other studies have reported variable results, with some finding no clear benefit from iron therapy 5.
• The optimal formulation and timing of iron administration, as well as patient characteristics predicting response, require additional study 3, 4.

Benefits and Risks of Iron Supplementation

• Iron supplementation has been associated with improved RLS symptoms, including a decrease in the International Restless Legs Syndrome score (IRLSS) 3, 4.
• Iron therapy may also improve quality of life, although the evidence is not consistent across studies 3, 4.
• The risk of adverse events with iron supplementation is generally considered low, with no significant difference in adverse events compared to placebo 5, 4.

Patient Selection and Monitoring

• Patients with RLS should be evaluated for iron deficiency, and iron supplementation should be considered for those with low serum ferritin levels 2, 6.
• The response to iron therapy may vary depending on patient characteristics, such as the presence of iron deficiency or other underlying medical conditions 4.
• Regular monitoring of RLS symptoms and serum iron levels is recommended to assess the effectiveness of iron supplementation and adjust treatment as needed 2, 4.