What is the appropriate treatment for Restless Legs Syndrome (RLS) in pregnancy?

Treatment of Restless Legs Syndrome in Pregnancy

For RLS in pregnancy, begin with iron supplementation if ferritin ≤75 ng/mL or transferrin saturation <20%, combined with non-pharmacological interventions, as the 2025 American Academy of Sleep Medicine guidelines explicitly state that prescribers must consider pregnancy-specific safety profiles and avoid standard pharmacological agents used in non-pregnant patients. 1

Initial Assessment and Iron Status

Check serum ferritin and transferrin saturation in all pregnant women with RLS, ideally in the morning after avoiding iron-containing supplements for at least 24 hours. 1 This is critical because:

• Iron deficiency is a major contributor to RLS in pregnancy, affecting approximately 20% of pregnant women 2
• Supplementation thresholds differ from general population: treat if ferritin ≤75 ng/mL or transferrin saturation <20% 1
• Both oral and IV iron formulations can be used during pregnancy when indicated 1, 3

Address Exacerbating Factors First

Before considering any medications, eliminate substances and drugs that worsen RLS: 1

• Discontinue caffeine and alcohol 1
• Avoid antihistamines, serotonergic medications (SSRIs), and antidopaminergic agents 1, 4
• Screen for and treat obstructive sleep apnea if present 1

Non-Pharmacological Interventions

Non-pharmacological approaches are the primary recommended treatment during pregnancy: 2, 3

• Regular moderate exercise (particularly leg-focused activities) 5, 3
• Pneumatic compression devices for the legs 5
• Reassurance that symptoms typically resolve postpartum 3
• Sleep hygiene optimization 3

Evidence shows that exercise, compression devices, and certain physical therapies significantly reduce RLS severity compared to no treatment, making them safe first-line options during pregnancy. 5

Pharmacological Treatment (When Conservative Measures Fail)

The 2025 AASM guidelines explicitly warn that standard RLS medications—gabapentin, pregabalin, and dopamine agonists—require careful pregnancy-specific safety consideration and are generally not recommended. 1 This represents a critical departure from non-pregnant management.

Medications That May Be Considered in Severe, Refractory Cases:

If symptoms remain severe despite iron supplementation and non-pharmacological measures: 6, 3

• Low-dose opioids (e.g., codeine, oxycodone) have more extensive pregnancy safety data than newer RLS medications and may be considered for severe symptoms 6, 3
• Clonazepam at low doses has been used, though benzodiazepines carry risks of neonatal withdrawal 6, 3
• Gabapentin has limited pregnancy data but may be considered when benefits outweigh risks in severe cases 6

Medications to Avoid:

Dopamine agonists (pramipexole, ropinirole) are NOT recommended during pregnancy due to insufficient teratogenic risk data, despite being first-line therapy outside pregnancy. 6, 3

Treatment Algorithm for Pregnancy

1. Confirm diagnosis using standard RLS criteria (urge to move legs, worse at rest, relieved by movement, worse in evening) 1, 4
2. Check iron studies (ferritin and transferrin saturation) 1
3. Supplement iron if ferritin ≤75 ng/mL or transferrin saturation <20% 1
4. Eliminate exacerbating factors (caffeine, alcohol, antihistamines, SSRIs) 1
5. Implement non-pharmacological interventions (exercise, compression devices) 5, 3
6. Reserve pharmacological treatment for severe, refractory cases only, using agents with better pregnancy safety profiles (low-dose opioids preferred over newer RLS medications) 6, 3

Critical Pitfalls to Avoid

• Do not use standard first-line RLS medications (gabapentin, pregabalin, dopamine agonists) without careful risk-benefit assessment, as pregnancy safety data is limited 1, 6
• Do not assume general population ferritin thresholds apply—use the higher threshold of ≤75 ng/mL for RLS treatment 1
• Do not overlook medication-induced RLS from antihistamines or antidepressants commonly used in pregnancy 1
• Do not prescribe dopamine agonists, which lack adequate teratogenic safety data despite being FDA-approved for RLS in non-pregnant patients 6, 3

Lactation Considerations

During breastfeeding, the same conservative approach applies, with iron supplementation and non-pharmacological measures preferred. 2, 3 Most RLS medications pass into breast milk in small amounts, requiring individualized risk-benefit discussion. 2, 3