Primidone Dosing for Essential Tremor
Start primidone at 25 mg at bedtime and titrate slowly to a target maintenance dose of 250 mg/day, as higher doses (750 mg/day) provide no additional benefit but significantly increase side effects and discontinuation rates. 1
Initial Dosing Strategy
- Begin with 25 mg at bedtime using the tablet formulation, as very low initial doses in suspension form (2.5 mg) do not improve tolerability and may actually worsen compliance 2
- The 25 mg starting dose helps minimize acute adverse reactions, which occur in approximately 32% of patients initiating primidone 3
- Acute side effects are most common in the first 48 hours of treatment and cannot be avoided by using lower initial doses 2
Titration Schedule
- Gradually increase the dose over 3 weeks to reach 150-250 mg/day 2, 1
- The optimal maintenance dose is 250 mg/day, which provides equivalent efficacy to 750 mg/day with significantly fewer adverse effects 1
- Doses can be divided (e.g., 125 mg twice daily) or given as a single bedtime dose depending on tolerability
Evidence for Low-Dose Efficacy
- A rigorous double-blind study with 1-year follow-up demonstrated that 250 mg/day was equally or more effective than 750 mg/day for controlling essential tremor 1
- The higher dose (750 mg/day) resulted in significantly more study discontinuations (p<0.04) and more frequent adverse effects (p<0.03) 1
- Both doses maintained therapeutic response throughout the entire 12-month treatment period 1
Expected Outcomes and Limitations
- Approximately 68% of patients will have no therapeutic benefit from primidone, making it ineffective as monotherapy in a substantial proportion of patients 3
- Among those who respond, about 54% report improvement in tremor symptoms 4
- Tolerance to therapeutic effect develops in approximately 13% of patients with chronic use 3
- Primidone is often used in combination with propranolol for patients who have partial response to either agent alone 5
Common Pitfalls and Management
- Acute adverse reactions are the primary barrier to successful treatment, occurring in nearly one-third of patients 3
- These early side effects (sedation, nausea, dizziness, ataxia) typically occur within the first 48 hours and cannot be prevented by ultra-low starting doses 2
- Chronic side effects are rare (0% in long-term studies), making primidone well-tolerated for those who successfully initiate therapy 3
- Patients should be counseled that initial side effects are common but typically resolve, and that persisting through the first few days often leads to successful long-term treatment
- If primidone fails to control disabling tremor, surgical options like deep brain stimulation should be considered 6