What is the recommended dosing for primidone (anticonvulsant medication) in the treatment of essential tremor?

Primidone Dosing for Essential Tremor

For essential tremor treatment, primidone should be initiated at 50 mg at bedtime for 3 days, then gradually increased to a maintenance dose of 250 mg/day, which is as effective as higher doses while causing fewer side effects. 1, 2

Initial Dosing Schedule

• Start with 50-100 mg at bedtime for days 1-3 1
• Increase to 50-100 mg twice daily for days 4-6 1
• Increase to 50-100 mg three times daily for days 7-9 1
• Target maintenance dose of 250 mg/day (can be given as a single dose or divided doses) 2

Efficacy and Dose Considerations

• Low-dose primidone (250 mg/day) is equally or more effective than high-dose primidone (750 mg/day) for controlling essential tremor 2
• Higher doses (750 mg/day) are associated with significantly more side effects and treatment discontinuation compared to lower doses (250 mg/day) 2
• Therapeutic response is maintained throughout 12 months of treatment at the 250 mg/day dose 2

Side Effects and Tolerability

• Acute adverse reactions occur in approximately 32% of patients starting primidone 3
• Common initial side effects include sedation, dizziness, nausea, and unsteadiness 4
• Very low initial doses and graduated titration schedules do not significantly improve primidone tolerability compared to standard low-dose initiation 4
• About 13% of patients may develop tolerance to primidone's therapeutic effect with chronic treatment 3

Clinical Considerations

• Primidone is a first-line medication for essential tremor along with propranolol 5
• If either primidone or propranolol alone does not provide adequate control, they can be used in combination 5
• Approximately 50% of patients with essential tremor experience improvement with medication therapy 5
• If medical therapy fails to control disabling tremor, surgical options like deep brain stimulation may be considered 5, 6

Alternative Medications

• If primidone is not tolerated, alternative medications include:
  • Propranolol (first-line alternative) 5
  • Benzodiazepines such as alprazolam (mean effective dose 0.75 mg/day) 7
  • Gabapentin or topiramate (second-line options) 5

Monitoring

• Serum blood level determinations may be necessary for optimal dosage adjustment in some cases 1
• The clinically effective serum level for primidone is between 5-12 mcg/mL 1
• Regular follow-up is recommended to assess efficacy and side effects 2

Remember that primidone should only be initiated if tremor causes functional disability, as there is currently no cure for essential tremor nor medications that can slow its progression 5.