What is the recommended dosing schedule for Buspirone (Buspar), including starting dose, titration, maximum dose, and adjustments for elderly patients or those with hepatic impairment?

Buspirone (Buspar) Dosing Guidelines

Start buspirone at 7.5 mg twice daily (15 mg/day total), increase by 5 mg/day every 2–3 days as tolerated to reach a target dose of 15–30 mg/day in divided doses, with a maximum of 60 mg/day; elderly patients and those with hepatic impairment require dose reductions. 1, 2, 3

Standard Adult Dosing

Initial Dose and Titration

• Begin with 7.5 mg twice daily (15 mg/day total) for the first few days 3
• Increase by 5 mg/day every 2–3 days until reaching the therapeutic range 3
• Target maintenance dose is 15–30 mg/day divided into 2–3 doses throughout the day 2, 3, 4
• Maximum dose is 60 mg/day, though most patients respond adequately to 15–30 mg/day 1, 2

Typical Dosing Schedule

• Most patients are successfully managed on 15–30 mg/day in clinical practice 2
• Administer in divided doses (typically 2–3 times daily) rather than once daily, as buspirone has a short elimination half-life of approximately 2.5 hours 1
• The standard therapeutic regimen is 10 mg three times daily (30 mg/day total) based on controlled trials 3

Special Population Adjustments

Elderly Patients

• Use the same dose range (15–30 mg/day) as in younger adults, as pharmacokinetics are not significantly affected by age 1, 5
• Mean effective dose in elderly patients is approximately 18 mg/day in controlled trials 5
• Start at 5 mg twice daily and titrate slowly to assess tolerability, particularly in elderly patients taking multiple medications for chronic conditions 5
• Elderly patients tolerate buspirone well even when receiving concomitant therapy for other medical conditions 5

Hepatic Impairment

• Reduce dose substantially in patients with hepatic impairment, as buspirone exposure increases 15-fold compared to healthy individuals 1
• The elimination half-life doubles in hepatic impairment (approximately 5 hours versus 2.5 hours in healthy patients) 1
• Consider starting at 5 mg twice daily and titrating very cautiously, as specific dosing guidelines are not established but the dramatic increase in drug exposure necessitates marked dose reduction 1

Renal Impairment

• Reduce dose by approximately 50% in patients with renal impairment, as both Cmax and AUC increase 2-fold after a single 20 mg dose 1
• Start at 5 mg twice daily and monitor closely for adverse effects 1

Administration Considerations

Food Effects

• Administer consistently with regard to food, as taking buspirone with food doubles both Cmax and AUC 1
• If starting with food, continue with food; if starting on an empty stomach, maintain that pattern to ensure consistent drug exposure 1

Pharmacokinetic Properties

• Peak plasma concentrations occur within 1 hour after oral administration 1
• Absolute bioavailability is only 4% due to extensive first-pass metabolism 1
• No drug accumulation occurs with multiple-dose administration over 9 days 1
• Pharmacokinetics are linear over the dose range of 10–40 mg 1

Long-Term Use and Discontinuation

Duration of Therapy

• Buspirone can be used safely for up to one year when chronic anxiety treatment is necessary 2
• Periodically reevaluate the need for continued therapy when treatment extends beyond several months 2
• Long-term anxiolytic therapy is not generally recommended, but buspirone has demonstrated safety for extended use when clinically indicated 2

Discontinuation

• Abrupt discontinuation after more than 6 months of therapy produces no withdrawal syndrome or rebound anxiety 2
• No tapering schedule is required when stopping buspirone, unlike benzodiazepines 2

Critical Drug Interactions

Medications That Increase Buspirone Levels

• Avoid or reduce buspirone dose substantially when coadministering with:
  • Verapamil or diltiazem (calcium channel blockers) 1
  • Erythromycin (macrolide antibiotic) 1
  • Itraconazole (azole antifungal) 1
• These CYP3A4 inhibitors substantially increase buspirone plasma concentrations and may require dose reductions of 50% or more 1

Medications That Decrease Buspirone Levels

• Rifampin decreases buspirone plasma concentrations almost 10-fold, likely rendering it ineffective 1
• Consider alternative anxiolytic therapy if rifampin is required 1

Medications With Minimal Interaction

• Cimetidine and alprazolam have negligible effects on buspirone pharmacokinetics 1

Clinical Efficacy Markers

Expected Response

• Buspirone provides effective antianxiety therapy at 30 mg/day (10 mg three times daily) in controlled trials 3
• Efficacy is comparable in elderly patients with anxiety states or neurotic depression 5
• In alcohol-dependent patients, buspirone at a mean dose of 20.5 mg/day reduces alcohol craving by 40% and improves anxiety and depression scores 4

Adverse Effects

• Buspirone has no significant effect on prolactin, growth hormone, or cortisol levels at therapeutic doses 3
• Mild adverse experiences occur but are generally well-tolerated 5
• Treatment discontinuation due to adverse effects is rare in clinical trials 5, 4

Common Pitfalls to Avoid

• Do not administer buspirone once daily, as its short half-life requires divided dosing for sustained anxiolytic effect 1
• Do not use standard doses in patients with hepatic impairment, as drug exposure increases 15-fold 1
• Do not combine with strong CYP3A4 inhibitors without dose reduction, as this substantially increases buspirone levels 1
• Do not expect immediate anxiolytic effects, as buspirone typically requires several days to weeks to achieve full therapeutic benefit, unlike benzodiazepines 2
• Do not assume elderly patients require lower doses than younger adults, as age does not significantly affect pharmacokinetics, though cautious titration is still prudent 1, 5