What are the treatment options for restless leg syndrome?

Treatment Options for 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, 2

Initial Assessment and 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, 2
• Provide iron supplementation if serum ferritin ≤75 ng/mL or transferrin saturation <20% 1, 2
• Address potential exacerbating factors, including alcohol, caffeine, antihistaminergic medications, serotonergic medications, antidopaminergic medications, and untreated obstructive sleep apnea 1, 2

First-Line Pharmacological Treatment

• Gabapentin is strongly recommended for adults with RLS (strong recommendation, moderate certainty of evidence) 1, 2
• Gabapentin enacarbil is strongly recommended for adults with RLS (strong recommendation, moderate certainty of evidence) 1, 2
• Pregabalin is strongly recommended for adults with RLS (strong recommendation, moderate certainty of evidence) 1, 2
• Before initiating alpha-2-delta ligands, evaluate risk factors for misuse and monitor for side effects including dizziness and somnolence 1

Iron Therapy Options

• Oral ferrous sulfate is conditionally recommended for patients with appropriate iron parameters (ferritin ≤75 ng/mL or transferrin saturation <20%) 1, 2
• IV ferric carboxymaltose is strongly recommended for patients with appropriate iron parameters who don't respond to oral therapy 1, 2
• IV low molecular weight iron dextran and IV ferumoxytol are conditionally recommended for patients with appropriate iron parameters 1

Second-Line and Alternative Treatments

• Extended-release oxycodone and other opioids are conditionally recommended, particularly for refractory cases or when treating augmentation from dopaminergic agents 1, 3
• Bilateral high-frequency peroneal nerve stimulation is conditionally recommended as a non-pharmacological option 1
• Compression devices, counterstrain manipulation, and infrared therapy may reduce RLS severity 4

Medications to Use with Caution or Avoid

• Dopaminergic agents (levodopa, pramipexole, ropinirole, rotigotine) are not recommended for standard use due to risk of augmentation - a paradoxical worsening of symptoms with long-term use 1, 2, 5
• The American Academy of Sleep Medicine specifically recommends against cabergoline (strong recommendation), bupropion, carbamazepine, clonazepam, and valproic acid for treating restless legs syndrome 1
• If dopaminergic agents are used, they should be reserved for short-term treatment in patients who prioritize immediate symptom relief over long-term adverse effects 1, 2

Special Populations

• For patients with end-stage renal disease and RLS, gabapentin is conditionally recommended (very low certainty of evidence) 1, 2
• IV iron sucrose is recommended if ferritin <200 ng/mL and transferrin saturation <20% for patients with RLS and end-stage renal disease 1, 2
• Vitamin C is conditionally recommended for patients with end-stage renal disease 1
• Treatment selection for RLS in pregnancy should consider pregnancy-specific safety profiles, with non-pharmacological approaches often preferred 2

Managing Augmentation

• Augmentation is characterized by worsening and earlier onset of symptoms in patients initially controlled on medication 1, 6
• Management options for augmentation include taking medication doses earlier in the day, splitting existing doses, or switching to non-dopaminergic agents 1, 3
• When transitioning from dopaminergic agents due to augmentation, add an alternative agent (alpha-2-delta ligand or opioid) first, then very slowly taper the dopaminergic medication 3