What is the recommended dose of gabapentin (Gabapentin) for Restless Legs Syndrome (RLS)?

Gabapentin Dosing for Restless Legs Syndrome

For restless legs syndrome, start gabapentin at 300 mg once daily in the evening (approximately 2 hours before symptom onset), then titrate upward by 300 mg every 3-7 days based on symptom response, targeting a maintenance dose of 1200-1800 mg/day divided into 2-3 doses, with a maximum of 2400 mg/day if needed. 1

Initial Dosing Strategy

• Begin with 300 mg taken 1-2 hours before typical symptom onset (usually early evening around 5-7 PM) 1
• The American Academy of Sleep Medicine strongly recommends gabapentin as first-line therapy for RLS with moderate certainty of evidence 1
• Single nighttime dosing is suboptimal because it fails to address daytime RLS symptoms that can occur in moderate-to-severe cases 1

Titration Protocol

• Increase by 300 mg every 3-7 days until adequate symptom control is achieved 1
• The recommended maintenance dose is 1800-2400 mg/day divided into three times daily dosing (e.g., morning, afternoon, and evening) 1
• Doses up to 3600 mg/day have been well-tolerated in clinical studies, though 2400 mg/day is typically the maximum needed for RLS 1
• If symptoms persist after reaching 900 mg/day total, continue escalating rather than staying at intermediate doses, as partial doses may cause more adverse effects than benefits 1

Alternative: Gabapentin Enacarbil (Prodrug Formulation)

• Gabapentin enacarbil 600 mg once daily at 5 PM with food is FDA-approved and provides more consistent absorption than immediate-release gabapentin 2, 3, 4
• The 600 mg dose significantly improves RLS symptoms compared to placebo, with mean IRLS score reductions of -13.6 versus -9.3 for placebo 4
• For patients with severe sleep disturbance associated with RLS, gabapentin enacarbil 1200 mg once daily may provide superior benefit 2
• Doses of 1800-2400 mg of gabapentin enacarbil show similar efficacy to 1200 mg but with higher rates of somnolence and dizziness 3, 4

Critical Monitoring and Side Effects

• Common side effects include somnolence and dizziness, which are typically transient and mild but dose-dependent 1, 3, 4
• Monitor for fall risk, particularly in elderly patients, though gabapentin has lower fall risk than dopamine agonists 1
• Assess for potential misuse in at-risk populations, as alpha-2-delta ligands have increasing evidence of misuse potential 1

Why Gabapentin Over Dopamine Agonists

• The American Academy of Sleep Medicine now suggests against standard use of dopamine agonists (pramipexole, ropinirole) due to augmentation risk—a paradoxical worsening of symptoms with earlier onset, increased intensity, and anatomic spread 1, 5
• This represents a major shift from older 2009 guidelines that recommended dopamine agonists as first-line 5
• Gabapentin avoids the augmentation phenomenon entirely 1

Essential Pre-Treatment Step

• Check morning fasting ferritin and transferrin saturation before starting gabapentin 1
• If ferritin ≤75 ng/mL or transferrin saturation <20%, add iron supplementation (oral ferrous sulfate or IV iron formulations), as correcting iron deficiency can significantly improve RLS symptoms independent of gabapentin 1
• Address exacerbating factors including alcohol, caffeine, antihistamines, SSRIs, and antipsychotics 1

Special Population: End-Stage Renal Disease

• For patients with ESRD on dialysis, start with 100 mg post-dialysis or 100 mg at bedtime, with maximum doses of 200-300 mg daily due to reduced clearance and increased risk of altered mental status 1
• Gabapentin is conditionally recommended for ESRD patients with very low certainty of evidence 1

Practical Dosing Example

• Week 1: 300 mg at 6 PM
• Week 2: 300 mg at 2 PM + 300 mg at 6 PM (600 mg/day total)
• Week 3: 300 mg at 10 AM + 300 mg at 2 PM + 300 mg at 6 PM (900 mg/day total)
• Week 4+: Continue increasing by 300 mg every 3-7 days until reaching 1800-2400 mg/day divided three times daily, or until symptoms are adequately controlled 1