What is the treatment approach for patients with restless leg syndrome (RLS) and essential tremor (ET)?

Treatment Approach for Restless Leg Syndrome and Essential Tremor

Alpha-2-delta ligands (gabapentin, gabapentin enacarbil, or pregabalin) should be used as first-line therapy for patients with restless leg syndrome (RLS), while essential tremor should be treated separately according to its specific management guidelines. 1

First-Line Treatment for Restless Leg Syndrome

• Check serum iron studies in all patients with clinically significant RLS, including ferritin and transferrin saturation, ideally in the morning after avoiding iron-containing supplements for at least 24 hours 1
• Consider iron supplementation if serum ferritin ≤75 ng/mL or transferrin saturation <20% 1
• Address potential exacerbating factors, including alcohol, caffeine, antihistaminergic medications, serotonergic medications, antidopaminergic medications, and untreated obstructive sleep apnea 1
• Use alpha-2-delta ligands as first-line pharmacological therapy:
  • Gabapentin (strong recommendation, moderate certainty of evidence) 1
  • Gabapentin enacarbil (strong recommendation, moderate certainty of evidence) 1
  • Pregabalin (strong recommendation, moderate certainty of evidence) 1

Medications to Avoid or Use with Caution in RLS

• Dopaminergic agents are not recommended for standard use due to risk of augmentation (paradoxical worsening of symptoms with long-term use):
  • Levodopa (conditional recommendation against, very low certainty) 1
  • Pramipexole (conditional recommendation against, moderate certainty) 1
  • Ropinirole (conditional recommendation against, moderate certainty) 1, 2
  • Rotigotine (conditional recommendation against, low certainty) 1
• Specifically avoid:
  • Cabergoline (strong recommendation against, moderate certainty) 1
  • Bupropion, carbamazepine, clonazepam, valproic acid, and valerian (conditional recommendations against) 1

Second-Line and Alternative Treatments for RLS

• For patients with appropriate iron parameters who don't respond to oral therapy:
  • IV ferric carboxymaltose (strong recommendation, moderate certainty) 1
  • IV low molecular weight iron dextran and IV ferumoxytol (conditional recommendation) 1
• For refractory cases:
  • Extended-release oxycodone and other opioids (conditional recommendation) - particularly effective for treating augmentation when decreasing or eliminating dopamine agonists 1, 3
• Non-pharmacological options:
  • Bilateral high-frequency peroneal nerve stimulation (conditional recommendation, moderate certainty) 1
  • Regular physical activity 4

Special Populations with RLS

• For patients with end-stage renal disease and RLS:
  • Gabapentin (conditional recommendation, very low certainty) 1
  • IV iron sucrose if ferritin <200 ng/mL and transferrin saturation <20% (conditional recommendation, moderate certainty) 1
  • Vitamin C (conditional recommendation, low certainty) 1
• For pediatric RLS:
  • Ferrous sulfate (conditional recommendation, very low certainty) 1

Managing Augmentation in RLS

• Augmentation is characterized by earlier symptom onset during the day, increased symptom intensity, and spread of symptoms to other body parts 1
• Management options include:
  • Taking medication doses earlier in the day 1
  • Splitting existing doses into early evening and bedtime doses 1
  • Consider opioids for treating augmentation 1, 3
  • Maintain high serum ferritin levels to help prevent augmentation 3

Treatment Considerations for Essential Tremor

• While this evidence set focuses primarily on RLS, it's important to note that essential tremor requires a separate treatment approach
• First-line treatments for essential tremor typically include:
  • Propranolol (a beta-blocker)
  • Primidone (an anticonvulsant)
• For patients with both conditions, medication selection should consider potential interactions and overlapping side effects

Practical Treatment Algorithm

1. Assess and correct iron status if deficient (ferritin ≤75 ng/mL or transferrin saturation <20%)
2. Start with an alpha-2-delta ligand (gabapentin, gabapentin enacarbil, or pregabalin) for RLS 1
3. For essential tremor, initiate appropriate therapy (typically propranolol or primidone)
4. If RLS symptoms are inadequately controlled, consider:
   • Ensuring optimal dosing of alpha-2-delta ligand
   • Adding IV iron therapy if iron parameters indicate 1
   • Adding an opioid for refractory cases 1, 3
5. Monitor for augmentation if dopaminergic agents are used, keeping doses as low as possible 3