Introduction
Buspar (buspirone hydrochloride) is an anxiolytic medication chemically unrelated to benzodiazepines, barbiturates, or other sedative/anxiolytic drugs. First approved by the FDA in 1986, it represents a distinct class of anxiolytics with a unique mechanism of action and favorable side effect profile compared to traditional anti-anxiety medications.
Mechanism of Action
Buspirone demonstrates high affinity for serotonin 5-HT₁A receptors, acting as a partial agonist. Unlike benzodiazepines, it does not act on GABA receptors. Its anxiolytic effects appear to be mediated through serotonin neurotransmission modulation, particularly in the dorsal raphe nucleus. Buspirone also displays moderate affinity for dopamine D₂ receptors, acting as both an agonist and antagonist depending on brain region, and weak affinity for α₁-adrenergic receptors. The drug lacks significant anticonvulsant, muscle relaxant, or sedative properties characteristic of benzodiazepines.
Indications
- FDA-approved for the management of anxiety disorders
- Short-term treatment of generalized anxiety disorder (GAD)
- Off-label uses include:
- Augmentation therapy for depression - Treatment of aggression in dementia - Management of premenstrual syndrome - Treatment of serotonin syndrome symptoms
Dosage and Administration
Initial dosage: 7.5 mg twice daily Dosage titration: Increase by 5 mg daily every 2-3 days Usual therapeutic range: 20-30 mg daily in divided doses Maximum recommended dose: 60 mg daily Special populations:- Hepatic impairment: Reduce dose by 25-50%
- Renal impairment: Use caution; consider dose reduction
- Elderly: Start with 5 mg twice daily
- Pediatrics: Not established for patients under 18 years
Pharmacokinetics
Absorption: Rapidly absorbed but undergoes extensive first-pass metabolism; bioavailability approximately 4% Distribution: Volume of distribution ~5.3 L/kg; 86% plasma protein bound Metabolism: Extensive hepatic metabolism via CYP3A4; produces active metabolite 1-PP (1-pyrimidinylpiperazine) Elimination: Half-life ~2-3 hours; excreted primarily in urine (29-63%) and feces (18-38%) Time to peak concentration: 40-90 minutes Steady-state: Achieved within 2-3 daysContraindications
- Hypersensitivity to buspirone or any component of the formulation
- Concurrent use with monoamine oxidase inhibitors (MAOIs) due to risk of hypertensive crisis
- Severe hepatic impairment
- Concurrent use with linezolid or intravenous methylene blue
Warnings and Precautions
- Dizziness and drowsiness: May impair mental or physical abilities required for hazardous tasks
- CNS effects: Caution in patients with history of seizures or organic brain disorders
- Serotonin syndrome risk: Especially when used with other serotonergic drugs
- Withdrawal: Does not produce significant withdrawal symptoms but taper gradually after prolonged use
- Pregnancy: Category B - use only if clearly needed
- Lactation: Excreted in breast milk; use caution
- Elderly: Increased sensitivity possible; initiate at lower doses
Drug Interactions
Major interactions:- MAO inhibitors: Risk of hypertensive crisis (contraindicated)
- Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir): Increase buspirone levels 5-13 fold
- Strong CYP3A4 inducers (rifampin, carbamazepine): Decrease buspirone levels up to 90%
- Other CNS depressants: Additive sedation
- SSRIs/SNRIs: Increased risk of serotonin syndrome
- Digoxin: Increased digoxin levels
- Haloperidol: Increased haloperidol concentrations
- Warfarin: Potential increased anticoagulant effect
Adverse Effects
Common (>10%):- Dizziness (12%)
- Nausea (8%)
- Headache (6%)
- Nervousness (5%)
- Lightheadedness
- Excitement
- Insomnia
- Fatigue
- Blurred vision
- Dry mouth
- Chest pain
- Tachycardia
- Syncope
- Seizures
- Extrapyramidal symptoms
- Serum transaminase elevation
Monitoring Parameters
- Therapeutic response and anxiety symptoms
- CNS effects (dizziness, drowsiness, cognitive function)
- Signs of serotonin syndrome (agitation, hallucinations, tachycardia, hyperthermia)
- Liver function tests (periodically with long-term use)
- Blood pressure (especially when initiating therapy)
- Drug interactions assessment
Patient Education
- Take consistently with regard to meals
- Therapeutic effects may take 2-4 weeks to become apparent
- Do not abruptly discontinue without medical supervision
- Avoid alcohol and other CNS depressants
- Report any unusual movements, restlessness, or mood changes
- Use caution when driving or operating machinery until effects are known
- Inform all healthcare providers about buspirone use, especially before starting new medications
- Do not crush or chew tablets
References
1. FDA Prescribing Information: Buspar (buspirone hydrochloride) 2. Pharmacotherapy: A Pathophysiologic Approach, 11th Edition 3. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th Edition 4. Stahl's Essential Psychopharmacology, 5th Edition 5. Clinical Pharmacokinetics of Buspirone. Clin Pharmacokinet. 1997 Aug;33(2):103-21 6. Wilson TK, Tripp J. Buspirone. [Updated 2023 May 29]. In: StatPearls [Internet] 7. Journal of Clinical Psychiatry: Buspirone in the Treatment of Generalized Anxiety Disorder (2000) 8. American Journal of Psychiatry: Buspirone Efficacy in Generalized Anxiety Disorder (2001)