What is the best medication for a 26-week pregnant patient with restless legs syndrome?

Best Medication for Restless Legs Syndrome at 26 Weeks Pregnancy

Iron supplementation is the best first-line treatment for RLS in pregnancy, specifically oral ferrous sulfate if serum ferritin is ≤75 ng/mL or transferrin saturation is <20%, with gabapentin as the preferred pharmacological option if iron therapy fails or symptoms are severe. 1, 2

Immediate Assessment Required

Before any medication is prescribed, check morning fasting serum ferritin and transferrin saturation after avoiding iron-containing supplements for at least 24 hours. 3, 1 This is critical because iron deficiency is a reversible cause of RLS in pregnancy and pregnancy itself increases RLS risk 2-3 times compared to the general population. 4, 5

First-Line Treatment: Iron Supplementation

• Start oral ferrous sulfate immediately if ferritin ≤75 ng/mL or transferrin saturation <20%—this threshold is higher than general population guidelines and specific to RLS management. 1, 2
• Iron supplementation during pregnancy has a favorable safety profile and should be the initial intervention before considering other medications. 2, 4
• Recheck iron studies after 8-12 weeks of supplementation to ensure adequate repletion. 2

Pharmacological Treatment When Iron Therapy Is Insufficient

Gabapentin: Preferred Medication

• Gabapentin is the recommended pharmacological treatment for RLS in pregnancy when iron therapy alone is inadequate or symptoms are severe. 2, 6
• Start with 300 mg at bedtime and titrate to 900-1200 mg daily in divided doses (300 mg three times daily) based on symptom response. 2
• The American Academy of Sleep Medicine strongly recommends gabapentin as first-line therapy for RLS with moderate certainty of evidence, though pregnancy-specific data is limited. 1, 2
• Gabapentin has a more extensive safety record in pregnancy compared to dopamine agonists. 6

Alternative: Pregabalin

• Pregabalin may be considered as an alternative with twice-daily dosing if gabapentin is not tolerated. 2
• Like gabapentin, it is an alpha-2-delta ligand with strong evidence for RLS treatment outside pregnancy. 1

Medications to Avoid in Pregnancy

• Dopamine agonists (ropinirole, pramipexole, rotigotine) should NOT be used as standard therapy in pregnancy due to limited pregnancy safety data and high risk of augmentation (paradoxical worsening of symptoms). 2, 6
• The FDA label for ropinirole specifically notes that RLS trials excluded patients with pregnancy-related RLS. 7
• Opioids, while effective for refractory RLS, should be reserved for severe cases unresponsive to other treatments due to concerns about neonatal withdrawal and respiratory depression. 6, 8

Non-Pharmacological Interventions

• Eliminate exacerbating factors: avoid alcohol, caffeine (especially in evening), antihistamines, serotonergic medications (SSRIs), and antidopaminergic agents. 3, 1, 9
• Screen for and treat obstructive sleep apnea, which is more common in pregnancy and can worsen RLS. 2
• Consider compression devices, exercise, and mental alerting activities as adjunctive measures. 10, 8

Critical Pitfalls to Avoid

• Do not assume 600 mg of gabapentin is adequate—most patients require 900-1200 mg daily for therapeutic effect. 2
• Do not initiate dopamine agonists despite their FDA approval for RLS, as pregnancy safety data is insufficient and augmentation risk is high. 2, 6
• Do not skip iron studies—iron deficiency is present in many pregnant women with RLS and correcting it may eliminate the need for other medications. 1, 2

Monitoring and Follow-Up

• Reassess symptoms weekly during gabapentin dose titration to find the minimum effective dose. 2
• Monitor for gabapentin side effects including dizziness and somnolence. 1
• RLS symptoms typically improve or resolve after delivery, so long-term medication may not be necessary. 5