buspirone

General Information

Buspirone is a non-benzodiazepine anxiolytic (azapirone) used for generalized anxiety disorder and chronic anxiety symptoms. It does not act on GABA receptors and does not share the same dependence and withdrawal profile as benzodiazepines.

Clinical effect is delayed (often 2–4+ weeks), so buspirone is not a rescue medication for acute panic or agitation; it works best with scheduled dosing and measurement-based follow-up.

Because buspirone is not a controlled substance and is typically not intoxicating, it can be a good fit when misuse risk, cognitive impairment, or occupational driving concerns make benzodiazepines a poor option; it is also used as SSRI/SNRI augmentation for residual anxiety.

The buspirone compare view, the buspirone evidence feed, and the buspirone print page can support an anxiety plan that minimizes sedation and misuse risk.

Best suited for persistent anxiety (especially GAD) when sedation, fall risk, or misuse concerns make benzodiazepines undesirable; onset is delayed and requires expectation-setting. Benefit depends on adherence and consistent dosing rather than “as-needed” use; early follow-up is helpful, and stopping and switching or augmenting is common when there is no meaningful improvement after an adequate trial.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Partial agonist at serotonin 5-HT1A receptors, modulating serotonergic tone in anxiety circuits.

Lacks clinically meaningful GABA-A activity, which is why it is not a reliable agent for acute anxiolysis or benzodiazepine withdrawal.

Minimal direct sedative-hypnotic activity is why buspirone is often preferred in older adults or polypharmacy, but it also means it will not “knock down” acute agitation the way benzodiazepines can.

• 5-HT1A partial agonism (primary).
• Minimal direct sedative-hypnotic receptor activity compared with benzodiazepines or antihistamines.

Metabolism and Pharmacokinetics

• Metabolized primarily by CYP3A4 to multiple metabolites, including 1-PP.
• Oral half-life of unchanged buspirone is ~2–3 hours (label).
• Significant food effect; taking consistently with or without food reduces variability.
• Short half-life is why dosing is typically divided (BID–TID) and why missed doses can lead to symptom recurrence.

Dosing and Administration

• Start 7.5 mg twice daily (or 5 mg three times daily); increase by ~5 mg/day every 2–3 days as tolerated.
• Typical effective range 20–30 mg/day in divided doses; maximum 60 mg/day (label).
• Abrupt changes in adherence can reduce benefit given the short half-life.
• Buspirone is not used as a PRN rescue medication; scheduled dosing and reassessment after an adequate trial (often 4–6 weeks at a therapeutic dose) are typical before changing strategy.

Monitoring & Labs

• Follow-up within 2–4 weeks is commonly used to assess adherence, side effects, and whether anxiety symptoms are trending in the right direction.
• Dizziness and activation are commonly tracked during titration; slower titration can help if patients feel “wired” or unsteady.
• Interacting medications (CYP3A4 inhibitors/inducers) and food consistency (grapefruit) are worth reviewing when response changes.
• If no meaningful benefit after an adequate trial, stopping and switching or augmenting is common rather than continuing indefinitely.

Sources: FDA/DailyMed label; guideline statements.

Adverse Effects

Interactions

• MAOI coadministration is contraindicated (hypertensive reactions reported); allow adequate washout.
• CYP3A4 inhibitors increase exposure; inducers may reduce efficacy.
• Grapefruit juice is typically avoided (CYP3A4 interaction).
• When used with other serotonergic agents (SSRIs/SNRIs, triptans, linezolid, tramadol), education about serotonin toxicity symptoms is appropriate, with prompt reassessment if agitation, tremor, or autonomic instability develop.

Other Useful Information

• Expectation-setting for delayed onset and early follow-up (2–4 weeks) are commonly used to support adherence.
• Buspirone does not treat benzodiazepine withdrawal; framing it as a direct “substitute” during tapers can set unrealistic expectations.
• Often paired with psychotherapy and sleep/activation screening for a durable anxiety plan.
• For adherence, dosing is often linked to daily routines (morning/evening), and food timing is kept consistent; BID regimens may reduce missed midday doses when feasible.
• If there is no meaningful benefit after an adequate trial, reassess diagnosis (GAD vs panic vs substance-related anxiety), treat comorbid depression/PTSD, and consider switching or augmenting rather than escalating indefinitely.

References

1. Buspirone hydrochloride prescribing information — DailyMed (2025)
2. Evidence Based Pharmacological Treatment OF Anxiety Disorders — Depression and Anxiety (2014)
3. Azapirones for generalized anxiety disorder — The Cochrane Database of Systematic Reviews (2006)
4. Guidelines FOR THE Pharmacological Treatment OF Anxiety Disorders, Obsessive Compulsive Disorder AND Posttraumatic Stress Disorder IN Primary Care — International Journal of Psychiatry in Clinical Practice (2012)