What are the medication options for restless leg syndrome (RLS) accompanied by tremor?

Medication Options for Restless Leg Syndrome with Tremor

Alpha-2-delta ligands (gabapentin, gabapentin enacarbil, or pregabalin) are strongly recommended as first-line therapy for patients with restless legs syndrome (RLS), including those with accompanying tremor, due to their efficacy and lower risk of augmentation compared to dopaminergic agents. 1

First-Line Treatment Options

• Alpha-2-delta ligands are strongly recommended by the American Academy of Sleep Medicine with moderate certainty of evidence for RLS treatment 1

  • 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

• These medications are particularly beneficial for patients with RLS and tremor due to their mechanism of action that addresses both sensory symptoms and motor manifestations 1

Iron Therapy Considerations

• Check serum iron studies, including ferritin and transferrin saturation, in all patients with clinically significant RLS 1
• Consider iron supplementation if serum ferritin ≤75 ng/mL or transferrin saturation <20% 1
• Iron therapy options include:
  • Oral ferrous sulfate (conditional recommendation, moderate certainty) 1
  • IV ferric carboxymaltose for patients who don't respond to oral therapy (strong recommendation, moderate certainty) 1

Second-Line and Alternative Treatments

• Extended-release oxycodone and other opioids are conditionally recommended for refractory cases or when treating augmentation from dopaminergic agents 1
• Bilateral high-frequency peroneal nerve stimulation is conditionally recommended as a non-pharmacological option 1
• Dipyridamole is conditionally recommended (low certainty of evidence) 1

Medications to Use with Caution or Avoid

• Dopaminergic agents (levodopa, pramipexole, ropinirole, rotigotine) are not recommended for standard use due to risk of augmentation - a paradoxical worsening of symptoms with long-term use 1, 2
• Despite FDA approval for RLS treatment, the American Academy of Sleep Medicine suggests against standard use of ropinirole due to concerns about augmentation 2, 3
• The American Academy of Sleep Medicine specifically recommends against bupropion, carbamazepine, clonazepam, valproic acid, and valerian for treating RLS 1

Management of Augmentation

• Augmentation is characterized by worsening and earlier onset of symptoms in patients initially controlled on medication 1, 2
• Signs include 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 2
  • Splitting existing doses into early evening and bedtime doses 2
  • Considering opioids for treating augmentation 1
  • Switching to alpha-2-delta ligands 4

Special Considerations for Tremor

• Alpha-2-delta ligands may be particularly beneficial for patients with both RLS and tremor due to their mechanism of action on calcium channels 1
• Gabapentin has shown efficacy in treating various forms of tremor in addition to RLS symptoms 1
• Prior to initiating alpha-2-delta ligands, evaluate risk factors for misuse and monitor for side effects including dizziness and somnolence 1

Treatment Algorithm for RLS with Tremor

1. Assess and address iron status first (supplement if ferritin ≤75 ng/mL or transferrin saturation <20%) 1
2. Initiate first-line treatment with an alpha-2-delta ligand (gabapentin, gabapentin enacarbil, or pregabalin) 1
3. If inadequate response or intolerance to alpha-2-delta ligands, consider opioids (extended-release oxycodone) 1, 5
4. For patients with refractory symptoms, consider combination therapy or non-pharmacological options like bilateral high-frequency peroneal nerve stimulation 1
5. Regularly monitor for side effects and treatment efficacy 1