Can gabapentin be used to treat restless legs syndrome (RLS)?

Gabapentin for Restless Legs Syndrome

Gabapentin is recommended as a first-line treatment option for restless legs syndrome (RLS), particularly in patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD). 1

Efficacy and Evidence

Gabapentin has demonstrated significant efficacy in treating RLS through several mechanisms:

• As an alpha-2-delta ligand anticonvulsant, gabapentin works by binding to voltage-gated calcium channels in the central nervous system, reducing the release of excitatory neurotransmitters 1
• Multiple studies have shown gabapentin effectively reduces:
  • Subjective RLS symptoms 2
  • Periodic limb movements during sleep (PLMS) 3, 2
  • Sleep disturbances associated with RLS 4

A small but notable study demonstrated that gabapentin (mean dosage 800 mg, range 300-1,200 mg) provided similar efficacy to ropinirole in improving both sensorimotor symptoms and reducing periodic leg movements during sleep 3.

Dosing Considerations

• Standard dosing typically starts at 300 mg and can be titrated up based on symptom response 2
• For gabapentin enacarbil (a prodrug of gabapentin):
  • The FDA-approved dose is 600 mg once daily 5
  • Higher doses (1,200 mg) may provide additional benefits for patients with severe sleep disturbances associated with RLS, though with increased risk of side effects 5, 4
• Dose adjustment is necessary for patients with kidney impairment 1

Patient Selection and Special Populations

Gabapentin is particularly advantageous for:

• Patients with CKD or ESRD (with appropriate dose adjustment) 1
• Patients at risk for augmentation with dopaminergic agents 1
• Those with significant sleep disturbances associated with RLS 4

Monitoring and Side Effects

Common side effects to monitor include:

• Dizziness
• Somnolence
• Fatigue

These side effects are generally mild and often transient 3, 4.

Treatment Algorithm

1. First step: Assess iron status (ferritin and transferrin saturation) and supplement if deficient (ferritin ≤75 ng/mL or transferrin saturation <20%) 1
2. For patients with normal iron status:
   • Start gabapentin at 300 mg at bedtime 2
   • Titrate dose upward based on symptom response and tolerability
3. For patients with CKD/ESRD:
   • Use gabapentin as first-line therapy with appropriate dose adjustment 1
4. For severe cases with inadequate response:
   • Consider increasing dose (if using gabapentin enacarbil, may consider up to 1,200 mg for severe sleep disturbances) 5, 4
   • Consider combination therapy or alternative agents

Clinical Pearls

• Alpha-2-delta ligands like gabapentin have a more favorable long-term safety profile with less risk of augmentation compared to dopaminergic agents 1
• Regular monitoring of symptom response and side effects is essential
• Avoid abrupt discontinuation; taper gradually if stopping treatment
• Consider non-pharmacological approaches as adjuncts (exercise, sleep hygiene) 1

Gabapentin represents a valuable treatment option for RLS with demonstrated efficacy and a favorable safety profile, particularly for patients with renal impairment or those at risk for augmentation with dopaminergic agents.