What are the current treatment options for restless leg syndrome?

Current Treatment Options for Restless Leg Syndrome

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

Initial Assessment and Treatment Approach

Assessment of Iron Status

• Check serum ferritin and transferrin saturation in all RLS patients
• Iron supplementation recommended 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

First-Line Pharmacological Treatment

1. Alpha-2-delta ligands (strongly recommended):

   • 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 1
   • Dose adjustment required in kidney disease
   • Pregabalin: Alternative first-line option 1

2. Iron therapy:

   • Oral iron for most patients with iron deficiency
   • IV ferric carboxymaltose strongly recommended when appropriate iron parameters are met 1

Address Exacerbating Factors

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

Second-Line and Alternative Treatments

For Treatment-Resistant Cases

• Opioids: Extended-release oxycodone conditionally recommended for severe cases 1
• Dipyridamole: Conditionally recommended 1

Dopaminergic Agents

• Not recommended for standard use due to risk of augmentation with long-term use
• May be considered for short-term use when immediate symptom relief is prioritized
• Options include levodopa, pramipexole, ropinirole, and rotigotine 1, 2
• Ropinirole has demonstrated efficacy in clinical trials with significant improvement in RLS symptoms compared to placebo 2

Other Pharmacological Options

• Bupropion, carbamazepine, clonazepam, and valproic acid may be considered 1
• Cabergoline is strongly recommended against 1

Non-Pharmacological Interventions

• Physical interventions:

  • Bilateral high-frequency peroneal nerve stimulation conditionally recommended 1
  • Regular exercise, particularly aerobic and resistance training 1
  • Cool dialysate for patients on hemodialysis 1

• Sleep hygiene practices:

  • Consistent sleep-wake schedule
  • Limiting stimulants 1

Special Considerations

Treatment Resistance

For patients with inadequate response to first-line treatments:

1. Increase alpha-2-delta ligands to maximum tolerated dose
2. Add non-pharmacological approaches
3. Consider opioids or bilateral high-frequency peroneal nerve stimulation 1

Pregnancy

Treatment safety profiles differ significantly during pregnancy; careful consideration of options is necessary 1

Monitoring

• Periodically reassess iron status in patients with initial iron deficiency
• Monitor for side effects and treatment response with all medications 1

Common Pitfalls to Avoid

1. Failing to check iron status before initiating treatment
2. Long-term use of dopaminergic agents without monitoring for augmentation (worsening of symptoms, usually with earlier onset)
3. Overlooking exacerbating factors such as caffeine, alcohol, and certain medications
4. Inadequate dose titration of alpha-2-delta ligands
5. Misdiagnosis or underdiagnosis - RLS is often misdiagnosed or unrecognized for years 3

The treatment landscape for RLS has evolved significantly, with alpha-2-delta ligands now preferred over dopaminergic agents due to the risk of augmentation with the latter. This represents a paradigm shift from earlier approaches that favored dopaminergic medications as first-line therapy 4, 5, 6, 3.