What are the treatment options for Restless Leg Syndrome (RLS)?

Treatment Options for Restless Leg Syndrome

Gabapentin or gabapentin enacarbil should be used as first-line pharmacological treatment for restless legs syndrome (RLS), with iron supplementation when deficient. 1

Initial Assessment and Non-Pharmacological Approaches

Iron Status Evaluation

• Check serum ferritin and transferrin saturation in all RLS patients
• Iron supplementation indicated when:
  • Ferritin ≤75 ng/mL or transferrin saturation <20% 1
  • For ESRD patients: IV iron sucrose when ferritin <200 ng/mL and transferrin saturation <20% 1

Address Exacerbating Factors

• Eliminate or reduce alcohol and caffeine consumption
• Review and adjust medications that may worsen RLS
• Treat underlying obstructive sleep apnea if present 1

Non-Pharmacological Interventions

• Regular exercise, particularly aerobic and resistance training
• Consistent sleep-wake schedule
• Bilateral high-frequency peroneal nerve stimulation for treatment-resistant cases
• Cool dialysate for patients on hemodialysis 1

Pharmacological Treatment Algorithm

First-Line Treatments

1. Alpha-2-delta ligands
   • Gabapentin: Start at 300 mg 1-2 hours before bedtime
     • Titrate by 300 mg increments every 3-7 days
     • Target dose: 600 mg for moderate symptoms, 900-1200 mg for severe symptoms
     • Adjust dosing in patients with kidney disease
   • Gabapentin enacarbil: FDA-approved alternative formulation
   • Pregabalin: Strong alternative first-line option 1

Second-Line Treatments

1. Dopaminergic agents (short-term use only due to augmentation risk)
   • Ropinirole: Start at 0.25 mg once daily 1-3 hours before bedtime
     • Titrate based on response over 7 weeks to maximum 4 mg daily 2
   • Pramipexole
   • Rotigotine (transdermal patch)
   • Levodopa 1

Treatment-Resistant RLS

1. Opioids (for severe cases)

   • Extended-release oxycodone
   • Tramadol
   • Methadone 1

2. Other options

   • Dipyridamole
   • Consider combination therapy
   • IV iron therapy (ferric carboxymaltose preferred) 1

Special Considerations

Augmentation

Augmentation is a major concern with dopaminergic agents, characterized by:

• Earlier symptom onset
• Increased symptom intensity
• Spread of symptoms to other body parts
• Consider switching to alpha-2-delta ligands if augmentation occurs 1

Pregnancy

• Treatment safety profiles differ significantly during pregnancy
• Careful consideration of treatment options required 1

Chronic Kidney Disease

• Gabapentin is first-line for patients with CKD or ESRD and RLS
• Adjust dosing based on kidney function
• Consider IV iron sucrose for ESRD patients with iron deficiency 1

Treatment Monitoring

• Regularly reassess iron status in patients with initial iron deficiency
• Monitor for side effects and treatment response
• Periodically reevaluate need for continued therapy 1

The American Academy of Sleep Medicine strongly recommends gabapentin or gabapentin enacarbil as first-line treatment over dopaminergic agents due to the risk of augmentation with long-term dopaminergic therapy. This represents a significant shift from earlier treatment paradigms that favored dopamine agonists as first-line therapy 1, 3, 4. While dopaminergic agents like ropinirole have demonstrated efficacy in clinical trials 2, their use should be limited to short-term treatment in patients prioritizing immediate symptom relief.