What is the recommended dosing for Buspar (buspirone)?

Buspar (Buspirone) Dosing

Start buspirone at 5 mg twice daily (total 10 mg/day) and increase by 5 mg per day every 2-3 days until reaching the target dose of 15-30 mg/day divided into 2-3 doses, with a maximum of 60 mg/day. 1

Initial Dosing Strategy

• Begin with 5 mg twice daily (morning and evening) for the first few days 1
• This conservative starting dose minimizes side effects while establishing baseline tolerability 1
• The initial dose can be administered as 5 mg three times daily if preferred, though twice daily dosing may improve compliance 2, 3

Titration Schedule

• Increase by 5 mg per day every 2-3 days until therapeutic effect is achieved 1
• This gradual escalation allows assessment of tolerability at each dose level 1
• Most patients respond to 15-30 mg/day divided into 2-3 doses 1, 4
• The therapeutic range of 15-30 mg/day was successfully used in the majority of patients in long-term safety studies 4

Dosing Regimens

Twice daily (BID) vs. Three times daily (TID):

• For 30 mg total daily dose, either 15 mg BID or 10 mg TID are equally effective 2, 3
• BID dosing may offer better convenience and compliance without compromising efficacy or safety 2
• No significant differences in efficacy or adverse events between BID and TID regimens, except slightly higher palpitations with BID (5% vs 1%) 2

Maximum Dosing

• Maximum recommended dose is 60 mg/day (can be given as 20 mg three times daily) 1
• Doses up to 90 mg/day have been studied and found safe in clinical trials for major depression 5
• However, standard anxiety treatment rarely requires exceeding 60 mg/day 1

Special Populations

Elderly Patients:

• Use standard dosing but monitor more carefully for side effects 1
• The 5 mg twice daily starting dose is particularly appropriate for older adults 1
• Pharmacokinetics are not affected by age, so dose adjustments based solely on age are not required 6, 7

Hepatic Impairment:

• Cannot be recommended in severe hepatic impairment 6
• Plasma levels increase 15-fold and half-life doubles in hepatic impairment 6, 7
• If used in mild-moderate impairment, start with lower doses and titrate cautiously 6

Renal Impairment:

• Cannot be recommended in severe renal impairment 6
• Cmax and AUC increase 2-fold in renal impairment 6, 7
• Consider lower starting doses if mild-moderate impairment present 6

Critical Drug Interactions Requiring Dose Adjustment

Strong CYP3A4 Inhibitors (require substantial dose reduction):

• Itraconazole: Reduce to 2.5 mg once daily if coadministered (19-fold increase in AUC) 6
• Nefazodone: Reduce to 2.5 mg once daily if coadministered (up to 50-fold increase in AUC) 6
• Erythromycin: Reduce to 2.5 mg twice daily if coadministered (6-fold increase in AUC) 6
• Verapamil/Diltiazem: Reduce dose and monitor closely (4-5 fold increase in AUC) 6, 7

CYP3A4 Inducers (may require dose increase):

• Rifampin: May need to increase buspirone dose to maintain anxiolytic effect (90% decrease in AUC) 6, 7
• Anticonvulsants (phenytoin, phenobarbital, carbamazepine): May require dose adjustment 6

Administration Considerations

• Food increases absorption by 2-fold, so administer consistently with or without food 7
• Avoid grapefruit juice (9-fold increase in AUC with large amounts) 6
• Onset of anxiolytic effect typically occurs within 2-4 weeks 4
• No evidence of withdrawal syndrome with abrupt discontinuation after long-term use 4

Important Clinical Caveats

• Buspirone has low bioavailability (approximately 4%) due to extensive first-pass metabolism 7
• The active metabolite 1-pyrimidinylpiperazine (1-PP) may contribute to pharmacological activity 7
• No accumulation occurs with multiple dosing due to short half-life of 2.5 hours 7
• Must discontinue 48 hours before urine catecholamine testing to avoid false-positive results for pheochromocytoma 6
• Monitor prothrombin time if added to warfarin therapy (one case report of prolonged PT) 6