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

Gabapentin for Restless Legs Syndrome Treatment

Gabapentin is strongly recommended as a first-line treatment for adults with restless legs syndrome (RLS), with the American Academy of Sleep Medicine (AASM) giving it a strong recommendation based on moderate certainty of evidence. 1

First-Line Treatment Options for RLS

Alpha-2-Delta Ligands (First-Line)

• Gabapentin is recommended for adults with RLS with strong evidence supporting its efficacy in reducing RLS symptoms and improving sleep quality 1
• Gabapentin enacarbil (a prodrug of gabapentin) is also strongly recommended with moderate certainty of evidence 1
• Pregabalin is another alpha-2-delta ligand strongly recommended for RLS treatment 1

Special Populations

• In patients with end-stage renal disease (ESRD) and RLS, gabapentin is specifically suggested as an effective treatment option (conditional recommendation, very low certainty of evidence) 1

Dosing and Administration

• Standard gabapentin treatment typically begins at 300 mg and can be titrated up based on symptom response 2, 3
• Studies have shown effective dosing ranges from 300-1,200 mg, with a mean effective dose around 800 mg 2, 3
• For gabapentin enacarbil (prodrug), 600 mg once daily is the FDA-approved dose, though some patients with severe sleep disturbances may benefit from higher doses up to 1,200 mg 4

Efficacy Evidence

• Gabapentin significantly reduces:
  • Subjective RLS symptoms as measured by International Restless Legs Syndrome Study Group questionnaire scores 2, 3
  • Periodic leg movements during sleep (PLMS) and PLMS index as demonstrated in polysomnographic studies 2, 3
• Comparative studies have shown gabapentin to be similarly effective to dopamine agonists like ropinirole in treating RLS symptoms 2

Advantages Over Dopaminergic Agents

• Gabapentin does not cause augmentation (worsening of symptoms over time), which is a significant concern with dopamine agonists 5
• The AASM now suggests against the standard use of dopamine agonists (pramipexole, ropinirole, rotigotine) and levodopa due to concerns about augmentation with long-term use 1

Treatment Algorithm for RLS

1. First assess and address:

   • Iron status (supplement if ferritin ≤75 ng/mL or transferrin saturation <20%) 1
   • Exacerbating factors (alcohol, caffeine, antihistamines, serotonergic and antidopaminergic medications) 1

2. First-line pharmacological treatment:

   • Gabapentin, gabapentin enacarbil, or pregabalin 1
   • Alternative: IV iron (ferric carboxymaltose) if appropriate iron parameters 1

3. Second-line options:

   • Ferrous sulfate (if appropriate iron parameters) 1
   • Dipyridamole 1
   • Extended-release oxycodone and other opioids 1
   • Bilateral high-frequency peroneal nerve stimulation 1

Side Effects and Monitoring

• Common side effects of gabapentin include:
  • Somnolence and dizziness (most common) 4
  • Generally mild and transient adverse events 2, 6
• Long-term follow-up (6-10 months) has shown sustained improvement in RLS symptoms with gabapentin treatment 2

Medications to Avoid in RLS

• The AASM specifically recommends against:
  • Cabergoline (strong recommendation) 1
  • Bupropion 1
  • Carbamazepine 1
  • Clonazepam 1
  • Valproic acid 1