Buspirone

Buspirone is a non-sedating anxiolytic used for generalised anxiety disorder. It does not cause dependence, respiratory depression or withdrawal, and it does not work for acute anxiety or panic because the effect takes 2 to 4 weeks to build. It is often used as an add-on to an antidepressant, and it is a useful option when a benzodiazepine is unsuitable.

Classification. Anxiolytic, azapirone.

Mechanism. Partial agonist at serotonin 5-HT1A receptors, with weak antagonism at dopamine D2 receptors.

Pharmacokinetics. Rapidly absorbed but with extensive first-pass metabolism (bioavailability about 4%), so levels vary widely between patients. Food slows first-pass metabolism and raises levels, so take it consistently with or without food. Metabolised by CYP3A4 to 1-PP, an active metabolite. Half-life 2 to 3 hours.

All regimens are oral with no loading dose.

Generalised anxiety disorder, adults.

• Start 5 mg two or three times daily (or 7.5 mg twice daily).
• Titration: increase by 5 mg daily every 2 to 3 days based on response.
• Usual 15 to 30 mg daily in two or three divided doses. Maximum 60 mg daily (45 mg in some labels).
• Duration: review at 4 weeks; continue for 6 to 12 months if effective.

Add-on to an antidepressant (off-label, specialist use). 15 to 60 mg daily, started at 5 mg twice daily.

Dose limits. Older adults: start 5 mg once or twice daily and titrate slowly. Strong CYP3A4 inhibitors (itraconazole, ketoconazole, clarithromycin, ritonavir): start 2.5 mg daily and keep the total low. Mild to moderate liver or kidney impairment: lower doses and slower titration.

Contraindications. Concurrent monoamine oxidase inhibitor or within 14 days of stopping one, severe liver impairment, severe kidney impairment, hypersensitivity.

Serious adverse effects. Serotonin syndrome (with other serotonergic medicines), hypertensive crisis (with monoamine oxidase inhibitors), akathisia, dystonia and other movement disorders (rare), restless legs, seizures (rare).

Common adverse effects. Dizziness, nausea, headache, nervousness, light-headedness, excitement, insomnia.

Interactions. Monoamine oxidase inhibitors are contraindicated. Antidepressants (SSRIs, SNRIs, tricyclics), tramadol and linezolid add serotonergic risk. Strong CYP3A4 inhibitors (azole antifungals, macrolides, ritonavir, diltiazem, verapamil, grapefruit juice) raise levels several-fold. Rifampicin, carbamazepine, phenytoin and St John’s wort lower levels sharply, so a response may be lost in patients on tuberculosis treatment. Haloperidol levels may rise.

Common prescribing errors. Expecting immediate relief and escalating the dose too early; using it for panic or acute anxiety; combining with a monoamine oxidase inhibitor; not allowing for CYP3A4 inhibitors or inducers.

Special groups.

• Pregnancy: limited human data; avoid unless the benefit clearly outweighs the risk.
• Breastfeeding: excretion in milk is not well described; avoid.
• Children: not licensed.
• Older adults: start 5 mg once or twice daily.
• Kidney impairment: avoid in severe impairment; lower doses otherwise.
• Liver impairment: avoid in severe impairment; lower doses otherwise.

Formulations. Tablets 5 mg, 10 mg, 15 mg and 30 mg. Take in divided doses, always in the same relation to food.

Baseline. Anxiety severity, current antidepressants and other serotonergic medicines, medicines list for CYP3A4 inhibitors and inducers, liver and kidney function, pregnancy status.

Monitoring. Review response and tolerability at 2 to 4 weeks; if there is no benefit by 4 to 6 weeks at a full dose, change treatment. Ask about dizziness, nausea and movement symptoms.

Stopping. No dependence or withdrawal syndrome; reduce over 1 to 2 weeks if the dose is high, or stop and monitor for return of anxiety.

Referral and escalation. Refer to psychiatry if anxiety remains severe after 8 to 12 weeks at a full dose or if there is comorbid depression, substance misuse or suicidality. Fever, agitation, tremor and sweating on a combination of serotonergic medicines needs urgent assessment for serotonin syndrome.