What is the treatment for restless leg syndrome?

Treatment for Restless Leg Syndrome

For adults with restless leg syndrome (RLS), first-line treatment should be gabapentin, pregabalin, or gabapentin enacarbil, as these medications have strong evidence supporting their efficacy with moderate certainty of evidence. 1

Initial Assessment and Management

Before initiating pharmacological treatment:

1. Check iron status: Measure serum ferritin and transferrin saturation in all patients with RLS. Testing should be done in the morning after avoiding iron-containing supplements/foods for 24 hours 1

   • If ferritin ≤ 75 ng/mL or transferrin saturation < 20%: Consider oral or IV iron supplementation
   • If ferritin between 75-100 ng/mL: Consider IV iron only

2. Address exacerbating factors:

   • Eliminate alcohol and caffeine consumption
   • Discontinue or modify medications that may worsen RLS (antihistamines, serotonergic agents, antidopaminergic medications)
   • Treat underlying obstructive sleep apnea if present 1

Treatment Algorithm

First-Line Treatments (Strong Recommendations)

• Alpha-2-delta ligands:
  • Gabapentin (standard formulation)
  • Gabapentin enacarbil (extended-release)
  • Pregabalin

These medications have strong recommendations with moderate certainty of evidence 1

Second-Line Treatments (When Iron Status is Low)

• Iron therapy (conditional recommendation, moderate certainty):
  • Oral ferrous sulfate for patients with ferritin ≤ 75 ng/mL or transferrin saturation < 20% 1
  • IV iron options for those with appropriate iron parameters:
    • IV ferric carboxymaltose (strong recommendation)
    • IV low molecular weight iron dextran (conditional recommendation)
    • IV ferumoxytol (conditional recommendation)

Alternative Treatments (Conditional Recommendations)

• Dipyridamole (conditional recommendation, low certainty) 1
• Opioids including extended-release oxycodone (conditional recommendation, moderate certainty) - reserved for severe cases 1, 2
• Bilateral high-frequency peroneal nerve stimulation (conditional recommendation, moderate certainty) 1

Treatments to Avoid or Use with Caution

The AASM specifically suggests against the standard use of:

• Levodopa (risk of augmentation with long-term use)
• Dopamine agonists (pramipexole, ropinirole, rotigotine) due to risk of augmentation
• Bupropion
• Carbamazepine
• Clonazepam
• Valproic acid 1

Special Populations

End-Stage Renal Disease

• Gabapentin (conditional recommendation, very low certainty)
• IV iron sucrose for patients with ferritin < 200 ng/mL and transferrin saturation < 20%
• Vitamin C may provide benefit 1, 3

Pregnancy

• RLS is common during pregnancy
• Consider the pregnancy-specific safety profile of each treatment 1

Monitoring and Follow-up

• Regularly reassess iron status, especially with symptom worsening
• Monitor for augmentation (paradoxical worsening of symptoms) with dopaminergic treatments, characterized by:
  • Earlier symptom onset
  • More intense symptoms
  • Spread of symptoms to other body parts 2

Non-pharmacological Approaches

While formal studies are limited, the following may help:

• Good sleep hygiene
• Massage of affected legs
• Hot baths
• Mentally demanding tasks during periods of rest 4

The treatment approach should prioritize alpha-2-delta ligands (gabapentin, pregabalin) as first-line therapy due to their efficacy and lower risk of augmentation compared to dopaminergic agents, which were traditionally used but now have fallen out of favor due to long-term complications 1, 2.