Buspirone for Generalized Anxiety Disorder
Start buspirone at 5 mg twice daily and titrate gradually to 20-30 mg/day in divided doses (maximum 60 mg/day) for the treatment of generalized anxiety disorder. 1, 2
Initial Dosing Strategy
- Begin with 5 mg twice daily as recommended by the American Academy of Family Physicians 1
- The FDA label confirms buspirone is indicated for management of anxiety disorder or short-term relief of anxiety symptoms, particularly in patients whose diagnosis corresponds to GAD 2
- This low starting dose minimizes initial side effects while establishing therapeutic benefit 1
Titration Schedule
- Increase by 5 mg increments every 2-3 days as tolerated to reach the target therapeutic range 1
- Target dose: 20-30 mg/day in divided doses (either twice or three times daily) 1, 3
- Maximum dose: 60 mg/day 1, 2
- Both twice-daily (15 mg BID) and three-times-daily (10 mg TID) regimens at 30 mg/day show equivalent efficacy and safety, though BID dosing may improve compliance 3, 4
Timeline for Response
- Expect 2-4 weeks for therapeutic effect to become apparent 5, 6
- This delayed onset is a critical counseling point—patients should not expect immediate relief like they would with benzodiazepines 6
- Buspirone is most appropriate for patients who do not demand immediate gratification and can tolerate gradual symptom improvement 6
Optimal Patient Selection
- Best suited for mild to moderate anxiety/agitation 5, 1
- Particularly appropriate for chronic anxiety, elderly patients, and those with coexisting mild depressive symptoms (HAM-D scores 12-17) 6, 7
- Avoid in panic disorder—studies have been inconclusive and buspirone is not recommended for routine panic disorder treatment 6
- Ideal for patients requiring long-term treatment without risk of dependence, tolerance, or cognitive impairment 1
Duration of Treatment
- Efficacy demonstrated in controlled trials for 3-4 weeks, though one study showed safe use for 1 year 2
- The FDA label states that long-term use beyond 3-4 weeks has not been systematically studied in controlled trials, but physicians may use it for extended periods with periodic reassessment 2
Safety Profile and Monitoring
- Does not cause tolerance, dependency, or cognitive impairment—major advantage over benzodiazepines 1
- Most common adverse effects: dizziness, headache, nausea, nervousness, and lightheadedness 4, 8, 7
- Buspirone-treated patients experience significantly more nausea, dizziness, somnolence, and sweating compared to placebo 7
- Discontinue 48 hours before urine catecholamine testing to avoid false-positive results for pheochromocytoma 2
Critical Drug Interactions
- CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, grapefruit juice) increase buspirone levels—reduce buspirone dose 2
- CYP3A4 inducers (e.g., rifampin) decrease buspirone levels—may need dose adjustment to maintain effect 2
- Monitor prothrombin time if combined with warfarin (one case report of prolonged PT) 2
- Cimetidine increases buspirone Cmax by 40% but has minimal effect on overall exposure 2
Special Populations
- Severe hepatic or renal impairment: Cannot be recommended due to increased plasma levels and prolonged half-life 2
- Elderly patients: No dose adjustment needed—pharmacokinetics and safety profile similar to younger adults 2
- Pregnancy Category B: Use only if clearly needed; no fertility impairment or fetal damage in animal studies 2
- Nursing mothers: Avoid if clinically possible—excretion in human milk unknown 2
- Pediatric patients (6-17 years): Not effective—no significant differences from placebo in two 6-week trials 2
Common Pitfalls to Avoid
- Do not expect immediate relief—counsel patients about the 2-4 week onset to prevent premature discontinuation 5, 6
- Do not use for panic disorder—evidence is inconclusive and other agents are preferred 6
- Do not combine with severe hepatic/renal disease—contraindicated due to altered pharmacokinetics 2
- Do not forget to adjust for CYP3A4 interactions—significant impact on buspirone levels 2