What is the recommended treatment for restless leg syndrome?

Treatment of Restless Legs Syndrome (RLS)

For adults with restless legs syndrome, first-line pharmacological treatment should be gabapentin, gabapentin enacarbil, or pregabalin rather than dopamine agonists due to their superior long-term efficacy and lower risk of augmentation. 1

Initial Management Steps

1. Address exacerbating factors:

   • Eliminate alcohol and caffeine consumption
   • Discontinue medications that worsen RLS (antihistamines, serotonergic drugs, antidopaminergic medications)
   • Treat untreated obstructive sleep apnea 1

2. Check iron status:

   • Test serum ferritin and transferrin saturation (morning testing, avoid iron supplements 24h prior)
   • Initiate iron supplementation if:
     • Ferritin ≤75 ng/mL or transferrin saturation <20% (oral or IV iron)
     • Ferritin between 75-100 ng/mL (IV iron only)
     • For children: ferritin <50 ng/mL (oral or IV formulations) 1

Pharmacological Treatment Algorithm

First-line treatments (strong recommendations):

• Alpha-2-delta ligands:
  • Gabapentin enacarbil
  • Gabapentin
  • Pregabalin 1

Second-line treatments (conditional recommendations):

• Iron therapy (when appropriate based on iron status):

  • IV ferric carboxymaltose (strong recommendation)
  • IV low molecular weight iron dextran
  • IV ferumoxytol
  • Oral ferrous sulfate 1

• Other options:

  • Dipyridamole
  • Extended-release oxycodone and other opioids (for severe refractory cases)
  • Bilateral high-frequency peroneal nerve stimulation 1

Special populations:

• End-stage renal disease (ESRD):

  • Gabapentin (dose-adjusted)
  • IV iron sucrose (if ferritin <200 ng/mL and transferrin saturation <20%)
  • Vitamin C 1

• Pregnancy:

  • Consider pregnancy-specific safety profile of each treatment 1

Treatments to Avoid or Use with Caution

• Dopamine agonists (not recommended as first-line due to augmentation risk):

  • Pramipexole, ropinirole, rotigotine should be avoided as standard treatment
  • May be considered for short-term use in patients who prioritize immediate symptom relief over long-term adverse effects 1, 2

• Strongly avoid:

  • Cabergoline (strong recommendation against use) 1
  • Bupropion
  • Carbamazepine
  • Clonazepam
  • Valproic acid 1

Managing Augmentation

If a patient develops augmentation (iatrogenic worsening of symptoms) while on dopamine agonists:

1. Add an alpha-2-delta ligand or opioid
2. Once adequate symptom control is achieved with the second agent, very slowly taper and discontinue the dopamine agonist 2

Non-pharmacological Approaches

Consider these approaches as adjunctive therapy:

• Exercise
• Compression devices
• Repetitive transcranial magnetic stimulation
• Acupuncture 3

Monitoring and Follow-up

• Regularly reassess iron status
• Monitor for medication side effects
• For patients on dopamine agonists, watch for signs of augmentation (earlier symptom onset, increased severity, anatomic spread of symptoms) 2
• For patients on opioids, implement appropriate monitoring protocols 4

By following this evidence-based approach, most patients with RLS can achieve significant symptom relief and improved quality of life, while minimizing the risk of treatment-related complications like augmentation.