Can the dose of buspirone be increased in an elderly male patient, and is primidone suitable for his bilateral tremor?

Buspirone Dose Escalation and Primidone for Essential Tremor in Elderly Patients

Yes, buspirone can be increased from the current dose, and primidone is an appropriate first-line agent for bilateral essential tremor in elderly patients, though it requires careful initiation due to high rates of acute intolerance.

Buspirone Dose Adjustment

Current Dosing and Room for Escalation

• The typical maintenance dose of buspirone for anxiety is 15-30 mg/day divided into 2-3 doses, with a maximum recommended dose of 60 mg/day 1
• If the patient is currently on 5 mg TID (15 mg/day total), there is substantial room to increase the dose toward the typical maintenance range of 20-30 mg/day 1
• Dose increases should be made in increments of 5 mg/day every 2-3 days as tolerated 1

Special Considerations for Elderly Patients

• No significant pharmacokinetic differences exist between elderly and younger patients for buspirone, so standard dosing applies 1
• However, elderly patients may have greater sensitivity to side effects, warranting gradual titration 1
• In elderly patients with hepatic or renal impairment, buspirone levels can increase 4-13 fold, requiring dose reduction or avoidance in severe impairment 1

Critical Drug Interaction Alert

• If this patient is on rifamycins (rifampin, rifabutin, rifapentine) for any reason, buspirone concentrations will be substantially decreased, potentially requiring dose increases or use of an alternate medication 2
• Clinical monitoring is recommended when buspirone is used with rifamycins, and dose adjustments may be necessary 2

Primidone for Bilateral Essential Tremor

Evidence Supporting Primidone as First-Line Therapy

• Primidone is highly effective for essential tremor, reducing tremor amplitude by approximately 60% even with single doses 3
• Primidone demonstrates superior efficacy compared to propranolol in head-to-head trials 3, 4
• Low doses (50-250 mg/day) are as effective as high doses (up to 1000 mg/day), making lower dosing preferable to minimize side effects 3

Initiation Protocol for Elderly Patients

Critical: The major challenge with primidone is acute intolerance, affecting 32% of patients in the first 48 hours 5, 4

Recommended Starting Regimen (FDA-Approved)

For patients 8 years and older 6:

• Days 1-3: 100-125 mg at bedtime 6
• Days 4-6: 100-125 mg twice daily 6
• Days 7-9: 100-125 mg three times daily 6
• Day 10 onward: 250 mg three times daily (maintenance) 6

Alternative Lower-Dose Initiation

• Research suggests starting with 25 mg doses (using tablets) rather than ultra-low suspension doses, as very gradual titration did not improve tolerability 5
• The key is warning patients about acute reactions (vertigo, nausea) in the first 48-72 hours and ensuring they persist through this period if tolerable 5, 7

Maintenance Dosing

• Usual maintenance: 250 mg three times daily (750 mg/day total) 6
• Maximum dose: 500 mg four times daily (2000 mg/day), though lower doses are typically sufficient 6
• Therapeutic serum levels: 5-12 mcg/mL 6

Tolerability Profile

• Acute adverse reactions occur in 32% of patients, primarily vertigo and nausea in the first 48 hours 4, 7
• Six of 20 patients (30%) in one study could not tolerate primidone due to acute side effects 7
• Chronic side effects are rare (0% in one long-term study), making primidone well-tolerated once past the initiation phase 4
• Tolerance to therapeutic effect develops in approximately 13% of patients with chronic use 4

Mechanism and Clinical Pearls

• The therapeutic effect is mediated predominantly by primidone itself, not its metabolite phenobarbital, as tremor control is lost when phenobarbital is substituted 3
• A single 250 mg dose can reduce tremor within 1-7 hours, before phenobarbital levels become detectable 3
• No correlation exists between serum levels and therapeutic response, so dosing should be guided by clinical effect rather than levels 3

Clinical Algorithm for This Patient

1. Assess renal and hepatic function before adjusting buspirone or starting primidone 1
2. Increase buspirone gradually (e.g., to 7.5 mg TID, then 10 mg TID) if anxiety symptoms are not adequately controlled 1
3. Initiate primidone at 100-125 mg at bedtime for the bilateral tremor 6
4. Warn the patient explicitly about likely acute side effects (dizziness, nausea) in the first 2-3 days and encourage persistence if tolerable 5, 7
5. Titrate primidone every 3 days according to the FDA protocol, targeting 250 mg TID as maintenance 6
6. Monitor for movement disorders with buspirone, though rare, as dystonia and tremor exacerbation have been reported with doses of 30-40 mg/day 8

Common Pitfall to Avoid

Do not use ultra-low initiation doses (2.5 mg suspension) for primidone thinking it will improve tolerability—research shows this approach does not reduce acute side effects and may worsen compliance 5. The standard tablet initiation at 100-125 mg is appropriate and evidence-based 6, 5.