What is the maximum recommended daily dose of buspirone (Buspar) and the appropriate dosing regimen when used as an augmentation agent for treatment‑resistant depression or anxiety?

Buspirone Maximum Dose and Augmentation Dosing

For buspirone monotherapy in anxiety, the maximum recommended dose is 60 mg/day (typically 30 mg twice daily), while for augmentation of antidepressants in treatment-resistant depression, the effective dose range is 20–30 mg/day divided into 2–3 doses. 1, 2

Maximum Dose for Anxiety Disorders

• The FDA-approved maximum daily dose of buspirone is 60 mg/day, though most patients are successfully managed on 15–30 mg/day divided into 2–3 doses. 3
• The American Academy of Family Physicians recommends starting buspirone at 5 mg twice daily and titrating to 15–30 mg per day in divided doses for anxiety treatment. 1
• Clinical trials have demonstrated safety and tolerability at doses up to 90 mg/day in patients with major depression and anxiety, though this exceeds standard recommendations. 4, 5

Buspirone as Augmentation for Treatment-Resistant Depression

Effective Augmentation Dosing

• When augmenting antidepressants for treatment-resistant depression, buspirone 20–30 mg/day produces marked clinical improvement, with 59% of patients showing complete or partial remission when added to SSRIs. 2
• The augmentation dose of 20–30 mg/day is lower than the maximum monotherapy dose but appears optimal for enhancing antidepressant response. 2

Comparative Efficacy: Buspirone vs. Bupropion Augmentation

• Bupropion augmentation is superior to buspirone augmentation for treatment-resistant depression. Low-quality evidence from the STAR*D trial shows that augmenting SSRIs with bupropion decreases depression severity more effectively than buspirone augmentation. 6
• Bupropion demonstrates significantly better tolerability than buspirone, with discontinuation rates of 12.5% for bupropion versus 20.6% for buspirone (P < 0.001). 6
• When citalopram monotherapy fails, augmentation with bupropion achieves similar remission rates (30.3%) as buspirone but with markedly fewer adverse-event discontinuations. 6

Dosing Regimen Comparison

Twice-Daily vs. Three-Times-Daily Dosing

• Buspirone 15 mg twice daily (BID) offers equivalent efficacy and safety to 10 mg three times daily (TID), with the BID regimen providing better convenience and potentially higher compliance. 7
• The only significant difference between regimens is a higher incidence of palpitations with BID dosing (5%) compared to TID dosing (1%). 7
• Most frequently reported adverse events for both regimens include dizziness, headache, and nausea, with no appreciable differences in vital signs, ECG, or laboratory results. 7

Critical Timing Considerations

• Buspirone requires 2–4 weeks to become effective, which is essential to communicate to patients to maintain compliance during the lag period before therapeutic benefit appears. 1
• For augmentation therapy, clinical improvement may be observed within 4–5 weeks of adding buspirone to existing antidepressant regimens. 2
• Among initial responders to buspirone augmentation, 79% who remained on combination therapy for at least 4 months were symptom-free at follow-up. 2

Safety and Long-Term Use

• Chronic buspirone use for up to 52 weeks is not associated with emergence of new or unexpected side effects, and abrupt discontinuation after more than 6 months produces no evidence of withdrawal syndrome. 3
• Buspirone is contraindicated in severe hepatic or renal impairment because it is metabolized by the liver and excreted by the kidneys, leading to increased plasma levels and prolonged half-life in these populations. 8
• Buspirone should be discontinued at least 48 hours prior to urine collection for catecholamines, as it may interfere with urinary metanephrine/catecholamine assays and produce false-positive results for pheochromocytoma. 8

Clinical Decision Algorithm

When to choose buspirone augmentation:

• Patient has failed SSRI monotherapy after 6–8 weeks at adequate doses 2
• Bupropion is contraindicated (seizure history, eating disorder, uncontrolled hypertension) 6
• Patient has mild-to-moderate anxiety as the predominant residual symptom 1

When to choose bupropion augmentation instead:

• Patient has treatment-resistant depression with low energy, apathy, or motivational deficits 6
• Patient is concerned about sexual dysfunction or weight gain from SSRIs 6
• Patient requires smoking cessation in addition to depression treatment 6
• Better tolerability profile is needed (lower discontinuation rates) 6

Monitoring Parameters

• Assess treatment response at 4–5 weeks for buspirone augmentation, with full evaluation by 6–8 weeks. 2
• Monitor for dizziness, headache, and nausea—the most common adverse effects with buspirone therapy. 7
• When discontinuing sertraline or other SSRIs in combination therapy, taper over 10–14 days to limit withdrawal symptoms. 1