What alternative treatments can be considered for a patient with essential tremors who is not responding to primidone?

Alternative Treatments for Essential Tremor When Primidone Is Ineffective

For patients with essential tremor not responding to primidone, propranolol should be considered as the next treatment option, followed by combination therapy, other medications like topiramate or gabapentin, or surgical interventions for refractory cases. 1

First-Line Alternatives

• Propranolol: The most established medication for essential tremor with over 40 years of demonstrated efficacy; can be used as monotherapy or in combination with primidone 1, 2

  • Typical dosage: Start at 40mg twice daily, can be titrated up to 240mg daily 2
  • Contraindications: Avoid in patients with chronic obstructive pulmonary disease, bradycardia, or congestive heart failure 1
  • Potential side effects: Lethargy, depression, dizziness, hypotension, exercise intolerance, and sleep disorders 1

• Alternative beta-blockers: If propranolol causes adverse effects, consider atenolol or metoprolol 2, 3

  • These may have fewer central nervous system side effects while still providing tremor control 3

Second-Line Options

• Combination therapy: Using primidone and propranolol together may provide better control than either medication alone 2

• Benzodiazepines: Particularly useful when tremor is exacerbated by stress or anxiety 2

  • Alprazolam has been shown to be equipotent to primidone in controlling essential tremor at a mean effective daily dose of 0.75mg 4
  • Clonazepam can provide benefit when primidone and propranolol do not provide adequate control 2

• Gabapentin: Can be effective as an alternative treatment 2, 3

  • Consider in patients with renal impairment where primidone or propranolol may be problematic

• Topiramate: May provide tremor control as a second-line agent 2, 3

  • Useful in patients who also have migraine headaches

Treatment Algorithm for Refractory Essential Tremor

1. Optimize current medication: Ensure patient has reached maximum tolerated dose of primidone before declaring treatment failure 1

2. Switch to propranolol or add it to the current primidone regimen 2

3. Try second-line oral medications if first-line treatments fail:

   • Gabapentin or topiramate 3
   • Benzodiazepines like alprazolam or clonazepam 2, 4

4. Consider botulinum toxin injections for focal tremors, particularly head or voice tremor 2, 5

   • Note: Hand injections may cause bothersome weakness and are not widely used 2

5. Evaluate for surgical options when medications fail due to:

   • Lack of efficacy at maximum doses
   • Dose-limiting side effects
   • Medical contraindications
   • Occupational limitations 1

Surgical Options for Medication-Refractory Tremor

• Deep brain stimulation (DBS): Provides adequate tremor control in approximately 90% of patients 2

  • Preferred for bilateral procedures to avoid adverse effects seen with bilateral ablative procedures 2

• Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy: Shows sustained tremor improvement of 56% at 4 years 1

  • Lower complication rate (4.4%) compared to radiofrequency thalamotomy (11.8%) and DBS (21.1%) 1
  • Contraindicated bilaterally or contralateral to a previous thalamotomy 1
  • Requires skull density ratio ≥0.40 and ability to undergo MRI 1

Important Considerations

• No medication can currently slow the progression of essential tremor; treatments are symptomatic only 2
• Currently available medications improve tremor in approximately 50% of patients 2, 3
• Surgical options provide adequate tremor control in approximately 90% of patients with refractory tremor 2
• Regular assessment of tremor severity and medication side effects is essential for optimal management 1