What are the treatment options for restless leg syndrome?

Treatment Options for Restless Legs Syndrome

The first-line treatment for restless legs syndrome (RLS) in adults should be alpha-2-delta ligands, specifically gabapentin, gabapentin enacarbil, or pregabalin, due to their strong evidence of efficacy and lower risk of augmentation compared to dopaminergic agents. 1, 2, 3

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 2, 3
• Address potential exacerbating factors, including alcohol, caffeine, antihistaminergic medications, serotonergic medications, antidopaminergic medications, and untreated obstructive sleep apnea 2, 3
• Consider iron supplementation if serum ferritin ≤75 ng/mL or transferrin saturation <20% 2, 3

First-Line Pharmacological Treatment

• Gabapentin enacarbil is strongly recommended for adults with RLS (strong recommendation, moderate certainty of evidence) 1, 2, 3
• Gabapentin is strongly recommended for adults with RLS (strong recommendation, moderate certainty of evidence) 1, 2, 3
• Pregabalin is strongly recommended for adults with RLS (strong recommendation, moderate certainty of evidence) 1, 2, 3

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, 3
• IV ferric carboxymaltose is strongly recommended for patients with appropriate iron parameters who don't respond to oral therapy 1, 2, 3
• 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, 3
• Dipyridamole is conditionally recommended (low certainty of evidence) 1

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, 3
• These agents may be considered only for short-term treatment in patients who prioritize immediate symptom relief over long-term adverse effects 1, 2, 3
• Cabergoline is strongly recommended against 3

Special Populations

• For patients with end-stage renal disease and RLS, gabapentin is conditionally recommended 2, 3
• IV iron sucrose may be considered for patients with ferritin <200 ng/mL and transferrin saturation <20% who have end-stage renal disease 3
• Treatment selection for RLS in pregnancy should consider pregnancy-specific safety profiles, with non-pharmacological approaches generally preferred 2, 3

Non-Pharmacological Approaches

• Regular physical activity/exercise should be recommended for symptom management 4, 5
• Other non-pharmacological interventions with some evidence of benefit include compression devices, acupuncture, and repetitive transcranial magnetic stimulation 4
• Good sleep hygiene and avoidance of alcohol, caffeine, and nicotine may improve symptoms 6

Managing Augmentation

• Augmentation is characterized by earlier symptom onset during the day, increased symptom intensity, and spread of symptoms to other body parts 3
• Management options include taking medication doses earlier in the day, splitting existing doses, or transitioning to non-dopaminergic agents 3
• Opioids may be particularly effective for treating augmentation when decreasing or eliminating dopamine agonists 3, 7

The treatment algorithm should prioritize alpha-2-delta ligands as first-line therapy, with appropriate iron supplementation when indicated, and careful consideration of the risks of augmentation when dopaminergic agents are used. Regular monitoring and adjustment of therapy based on symptom control and side effects is essential for optimal management of RLS.