Buspirone

Buspirone is an anxiolytic medication approved for generalized anxiety disorder. It is a nonbenzodiazepine agent that does not produce the sedation, cognitive impairment, or abuse potential commonly associated with benzodiazepines. It is primarily used for generalized anxiety disorder and is sometimes prescribed off-label for other anxiety conditions or as an adjunct in depression.

Buspirone acts as a partial agonist at the serotonin 5-HT1A receptor and interacts with other serotonergic and dopaminergic pathways. Its therapeutic effect is thought to arise from modulation of serotonergic signaling rather than enhancement of GABAergic inhibition. It has little to no substantial anticonvulsant, sedative, or muscle-relaxant properties.

Pharmacokinetics and administration: buspirone is taken orally and undergoes significant first-pass metabolism, resulting in variable bioavailability. It is metabolized in the liver, primarily via cytochrome P450 3A4, and is excreted in urine and feces. Peak levels occur within about an hour or two after dosing, and the drug is typically dosed several times per day. The parent compound has a relatively short half-life, while active metabolites extend the duration of action. Response usually requires several weeks of treatment.

Dosing and onset: typical starting doses are in the range of 5 mg to 7.5 mg two or three times daily, titrated to an effective range, commonly around 20–60 mg per day. Clinicians emphasize gradual titration due to variable tolerability. Unlike benzodiazepines, buspirone does not provide immediate relief of acute anxiety and is not considered a sedative.

Adverse effects and interactions: common side effects include dizziness, headaches, nausea, and nervousness. It has a lower risk of dependence, but can cause serotonin-related interactions when combined with other serotonergic agents. Contraindications include concurrent use with monoamine oxidase inhibitors and severe hepatic impairment. Clinicians should monitor for drug interactions with CYP3A4 inhibitors or inducers and caution against significant grapefruit juice consumption, which can raise buspirone levels.