How is With's Ekbom syndrome, also known as restless legs syndrome, managed?

Management of Willis-Ekbom Syndrome (Restless Legs Syndrome)

Alpha-2-delta ligands (gabapentin and pregabalin) should be used as first-line therapy for restless legs syndrome due to their favorable long-term safety profile compared to dopaminergic agents, which have significant risk of augmentation with prolonged use. 1, 2

Diagnostic Considerations

• Diagnosis requires four essential criteria:
  • Urge to move the legs, usually with uncomfortable sensations
  • Symptoms worsen during periods of rest
  • Symptoms improve with movement
  • Symptoms worsen in the evening or at night 3, 4

Treatment Algorithm

First-Line Treatments:

1. Iron Supplementation

   • Check serum ferritin and transferrin saturation
   • If ferritin ≤75 ng/mL or transferrin saturation <20%, initiate iron therapy 1, 2
   • Options:
     • Oral ferrous sulfate for most patients
     • IV ferric carboxymaltose (strong recommendation) for patients with inadequate response to oral iron 1
     • IV iron sucrose specifically for ESRD patients with ferritin <200 ng/mL 2

2. Alpha-2-Delta Ligands

   • Gabapentin or pregabalin 1, 2
   • Advantages: No risk of augmentation, effective for long-term use
   • Caution: Evaluate risk factors for misuse before initiating, as there is evidence of misuse potential 1
   • Dose adjustment needed for patients with kidney disease 2

Second-Line Treatments:

1. Short-term Dopaminergic Therapy (conditionally recommended against long-term use)

   • Ropinirole: Start at 0.25 mg once daily 1-3 hours before bedtime, titrate over 7 weeks to maximum 4 mg daily 5
   • Pramipexole: Mean effective dose ~0.3 mg 2
   • Warning: High risk of augmentation (paradoxical worsening of symptoms) with long-term use 1, 6

2. Opioids for Severe Cases

   • Extended-release oxycodone for moderate to severe RLS 1, 2
   • Particularly useful for patients who have failed other therapies 6
   • Caution: Monitor for respiratory depression and central sleep apnea 1

Non-Pharmacological Approaches

• Regular exercise, particularly aerobic resistance exercise 2
• Consistent sleep-wake schedule and good sleep hygiene 2
• Bilateral high-frequency peroneal nerve stimulation (conditional recommendation) 1, 2
• For patients on hemodialysis: Cool dialysate 2

Special Populations

1. End-Stage Renal Disease (ESRD)

   • Gabapentin (with dose adjustment) 1, 2
   • IV iron sucrose if ferritin <200 ng/mL and transferrin saturation <20% 2
   • Vitamin C supplementation 2

2. Pregnancy

   • Treatment requires special consideration due to different safety profiles 2
   • Non-pharmacological approaches should be prioritized

Managing Augmentation

Augmentation is the paradoxical worsening of symptoms due to dopaminergic treatment and represents a major challenge in RLS management 1, 6:

1. Keep dopamine agonist doses as low as possible 6
2. Consider switching to longer-acting dopamine agonists like rotigotine patch 6
3. Maintain high serum ferritin levels through supplementation 6
4. For established augmentation:
   • Gradually taper and discontinue dopamine agonists
   • Transition to alpha-2-delta ligands or opioids 6

Treatment Monitoring

• Regularly reassess iron status in patients with initial iron deficiency 2
• Monitor for side effects of medications:
  • Alpha-2-delta ligands: Sedation, dizziness
  • Dopamine agonists: Nausea, orthostasis, impulse control disorders, augmentation
  • Opioids: Respiratory depression, constipation

Common Pitfalls

1. Failing to check iron status before initiating pharmacological therapy
2. Long-term use of dopamine agonists without monitoring for augmentation
3. Not recognizing secondary causes of RLS (iron deficiency, pregnancy, renal failure, polyneuropathy)
4. Inadequate dose adjustment of medications in patients with kidney disease
5. Not discontinuing medications that can worsen RLS symptoms (certain antidepressants, antihistamines)

By following this algorithm and being vigilant for augmentation, clinicians can effectively manage Willis-Ekbom syndrome while minimizing long-term complications and optimizing quality of life.