What are the treatment options for restless leg syndrome?

Treatment Options for Restless Leg Syndrome

For adults with restless legs syndrome (RLS), first-line treatment should include gabapentin, gabapentin enacarbil, or pregabalin, along with addressing iron deficiency and eliminating exacerbating factors. 1

Initial Management Approach

Address Underlying Factors

• The first step in RLS management should be identifying and addressing exacerbating factors, including alcohol, caffeine, antihistaminergic medications, serotonergic medications, antidopaminergic medications, and untreated obstructive sleep apnea 1
• Test serum iron studies including ferritin and transferrin saturation in all patients with clinically significant RLS 1
• Testing should be done in the morning after avoiding iron-containing supplements and foods for at least 24 hours 1

Iron Supplementation

• Provide iron supplementation if serum ferritin ≤ 75 ng/mL or transferrin saturation < 20% 1
• Use oral iron (ferrous sulfate) for mild iron deficiency (conditional recommendation, moderate certainty) 1
• Use IV iron formulations when ferritin is between 75-100 ng/mL or when oral supplementation is ineffective 1
• IV ferric carboxymaltose is strongly recommended (strong recommendation, moderate certainty) 1
• Other IV iron options include low molecular weight iron dextran and ferumoxytol (conditional recommendations, very low certainty) 1
• For patients with end-stage renal disease and RLS, IV iron sucrose is suggested when ferritin < 200 ng/mL and transferrin saturation < 20% 1

First-Line Pharmacologic Treatment

Alpha-2-delta Ligands

• Gabapentin enacarbil is strongly recommended for adults with RLS (strong recommendation, moderate certainty) 1
• Gabapentin is strongly recommended for adults with RLS (strong recommendation, moderate certainty) 1
• Pregabalin is strongly recommended for adults with RLS (strong recommendation, moderate certainty) 1
• These medications have shown efficacy with lower risk of augmentation compared to dopaminergic agents 1

Second-Line and Alternative Treatments

Dopaminergic Agents

• The AASM suggests against standard use of dopaminergic agents due to risk of augmentation (a paradoxical worsening of symptoms with long-term use) 1
• If used, dopaminergic agents should be reserved for short-term treatment in patients who prioritize immediate symptom relief over long-term adverse effects 1
• Specific dopaminergic agents that may be considered with caution include:
  • Levodopa (conditional recommendation against standard use, very low certainty) 1
  • Pramipexole (conditional recommendation against standard use, moderate certainty) 1
  • Ropinirole (conditional recommendation against standard use, moderate certainty) 1, 2
  • Transdermal rotigotine (conditional recommendation against standard use, low certainty) 1
• The AASM strongly recommends against cabergoline use (strong recommendation, moderate certainty) 1

Other Pharmacologic Options

• Dipyridamole may be used (conditional recommendation, low certainty) 1
• Extended-release oxycodone and other opioids may be considered (conditional recommendation, moderate certainty) 1
• Bilateral high-frequency peroneal nerve stimulation is an option (conditional recommendation, moderate certainty) 1
• For patients with end-stage renal disease, vitamin C may be considered (conditional recommendation, low certainty) 1

Medications to Avoid

• Bupropion (conditional recommendation against, moderate certainty) 1
• Carbamazepine (conditional recommendation against, low certainty) 1
• Clonazepam (conditional recommendation against, very low certainty) 1
• Valproic acid (conditional recommendation against, low certainty) 1

Special Populations

Pregnancy

• RLS is common in pregnancy; treatment selection should consider pregnancy-specific safety profiles 1
• Non-pharmacologic approaches may be preferred during pregnancy 1, 3

End-Stage Renal Disease

• Gabapentin may be used in patients with RLS and end-stage renal disease (conditional recommendation, very low certainty) 1
• IV iron sucrose is suggested for patients with ferritin < 200 ng/mL and transferrin saturation < 20% 1

Non-Pharmacologic Approaches

• Regular physical activity and exercise should be recommended 3, 4
• Good sleep hygiene practices and avoidance of alcohol, caffeine, and nicotine may improve symptoms 4, 5
• Evidence is insufficient but preliminary for yoga, acupuncture, pneumatic compression devices, near-infrared light therapy, and cognitive-behavioral therapy 3