How is restless leg syndrome managed?

Management of Restless Legs Syndrome

Alpha-2-delta ligands (gabapentin, gabapentin enacarbil, or pregabalin) are strongly recommended as first-line therapy for patients with restless legs syndrome due to their efficacy and lower risk of augmentation compared to dopaminergic agents. 1

Initial Assessment and Non-Pharmacological Management

• Check serum iron studies, including ferritin and transferrin saturation, in all patients with clinically significant RLS, ideally in the morning after avoiding iron-containing supplements for at least 24 hours 1
• Consider iron supplementation if serum ferritin ≤75 ng/mL or transferrin saturation <20% (different from general population guidelines) 1
• Address potential exacerbating factors, including alcohol, caffeine, antihistaminergic medications, serotonergic medications, antidopaminergic medications, and untreated obstructive sleep apnea 1
• Regular physical activity should be recommended as a non-pharmacological intervention for symptom relief 2, 3

Pharmacological Treatment Algorithm

First-Line Therapy

• Alpha-2-delta ligands are strongly recommended as first-line therapy with moderate certainty of evidence 1:
  • Gabapentin 1
  • Gabapentin enacarbil 1
  • Pregabalin 1

Iron Therapy

• For patients with ferritin ≤75 ng/mL or transferrin saturation <20%:
  • Oral ferrous sulfate (conditional recommendation, moderate certainty) 1
  • IV ferric carboxymaltose for patients who don't respond to oral therapy (strong recommendation, moderate certainty) 1
  • IV iron sucrose for patients with end-stage renal disease and ferritin <200 ng/mL (conditional recommendation, moderate certainty) 1

Second-Line and Alternative Treatments

• Extended-release oxycodone and other opioids (conditional recommendation) for refractory cases or when treating augmentation from dopaminergic agents 1, 4
• Bilateral high-frequency peroneal nerve stimulation (conditional recommendation, moderate certainty) 1
• Vitamin C for patients with end-stage renal disease (conditional recommendation) 1

Medications to Avoid or Use with Caution

• The American Academy of Sleep Medicine suggests against the standard use of dopaminergic agents due to risk of augmentation 1:

  • Levodopa (conditional recommendation, very low certainty) 1
  • Pramipexole (conditional recommendation, moderate certainty) 1
  • Ropinirole (conditional recommendation, moderate certainty) 1
  • Transdermal rotigotine (conditional recommendation, low certainty) 1

• Specifically recommended against:

  • Cabergoline (strong recommendation, moderate certainty) 1
  • Bupropion, carbamazepine, clonazepam, and valproic acid (conditional recommendations) 1

Managing Augmentation

• Augmentation is characterized by worsening and earlier onset of symptoms in patients initially controlled on medication, particularly with dopamine agonists 1, 4
• Management strategies include 1, 4:
  • Taking medication doses earlier in the day
  • Splitting existing doses into early evening and bedtime doses
  • Adding an alpha-2-delta ligand or opioid while maintaining the dopamine agonist initially
  • Very slowly tapering the dopamine agonist once the second agent provides adequate relief 4

Special Populations

• For end-stage renal disease and RLS:

  • Gabapentin (conditional recommendation, very low certainty) 1
  • IV iron sucrose if ferritin <200 ng/mL and transferrin saturation <20% (conditional recommendation, moderate certainty) 1
  • Vitamin C (conditional recommendation) 1

• For pediatric RLS:

  • Oral iron supplementation for serum ferritin <50 ng/mL (conditional recommendation, very low certainty) 1
  • Monitor for side effects, particularly constipation 1

Non-Pharmacological Options

• Bilateral high-frequency peroneal nerve stimulation (conditional recommendation, moderate certainty) 1, 2
• Regular exercise has shown benefit in reducing RLS severity 2, 3
• Other interventions with some evidence but requiring further research include compression devices, acupuncture, and yoga 2, 3

The management of RLS requires careful consideration of iron status, appropriate medication selection, and vigilance for augmentation when using dopaminergic agents. Alpha-2-delta ligands are now preferred as first-line therapy due to their efficacy and better long-term side effect profile compared to dopamine agonists 1.