This page shows what was measured, who it was measured in, and what that does not settle.
What Buspirone does in the body
Anxiety
Buspirone binds tightly to one particular serotonin receptor and moderately to a dopamine receptor. It does not touch the receptor that benzodiazepines use, so it does not sedate, does not relax muscles and is not habit-forming — which is the whole reason it exists. Beyond that, its own prescribing information says the mechanism of action is unknown. It also takes a couple of weeks to do anything, so it cannot be taken when anxiety strikes.
What happened in people
Number needed to treat of 4.4 (95% CI 2.16 to 15.4) on the Clinical Global Impression scale across 36 trials and 5,908 participants
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
Buspirone hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Precautions (Drug Interactions, CYP3A4 inhibito… · a recorded source, not a stored snapshot
The only widely used anxiolytic that is neither a benzodiazepine nor an antidepressant, and neither a controlled substance nor carrying a suicidality boxed warning
Where it acts
Serotonin 5-HT1A receptors — presynaptic autoreceptors on raphe neurons and postsynaptic receptors in hippocampus and cortex; the label commits to neither
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 104 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Clinical Global Impression response in generalized anxiety disorder, azapirones against placebo, benzodiazepines, antidepressants, psychotherapy or kava
✓ The study showed what it set out to show
Who was studied
Cochrane review of azapirones for generalized anxiety disorder (Cochrane Database Syst Rev 2006;(3):CD006115)
How many people
5908
Study design
Systematic review and meta-analysis of 36 randomised trials
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Superior to placebo, with a calculated number needed to treat on the Clinical Global Impression scale of 4.4 (95% CI 2.16 to 15.4)
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Azapirones may be less effective than benzodiazepines, and superiority over antidepressants, kava or psychotherapy could not be concluded. Fewer participants stopped taking benzodiazepines than azapirones. Trial lengths ran four to nine weeks with one at 14, and the authors state that longer-term studies are needed for what is a chronic illness. The benefit was particularly evident in participants who had not previously taken a benzodiazepine.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 5, 7.5, 10, 15 and 30 mg, taken two or three times daily, and to be taken consistently either always with or always without food
Interval reported. 95% CI 2
Written into the record, not signed off as a reviewed claim.
Buspirone hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Precautions (Drug Interactions, CYP3A4 inhibito… · a recorded source, not a stored snapshot
Randomised, open augmentation with blinded telephone outcome rating; no placebo arm
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Hamilton remission 29.7% with bupropion (n=565) against 30.1% with buspirone (n=286); QIDS-SR-16 remission 39.0% against 32.9% and response 31.8% against 26.9%
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Bupropion produced a greater QIDS-SR-16 reduction (25.3% against 17.1%, p<0.04), a lower final score (8.0 against 9.1, p<0.02) and a lower dropout rate due to intolerance (12.5% against 20.6%, p<0.009). There was no placebo arm, so neither augmentation can be read as superior to no augmentation, and buspirone holds no antidepressant indication.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 5, 7.5, 10, 15 and 30 mg, taken two or three times daily, and to be taken consistently either always with or always without food
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Buspirone hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Precautions (Drug Interactions, CYP3A4 inhibito… · a recorded source, not a stored snapshot
Sequenced Treatment Alternatives to Relieve Depression (STAR*D) registry record (NCT00021528) · a recorded source, not a stored snapshot
Tolerability of buspirone over one year of continuous use, as summarised on the label
✓ The study showed what it set out to show
Who was studied
One-year open tolerability study (NDA 018731, Indications and Usage)
How many people
264
Study design
Long-term open-label exposure study
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
The label states 264 patients were treated with buspirone for one year "without ill effect"; no efficacy result is reported
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. This is the only long exposure data on the document and it addresses safety, not effectiveness. The same section states that effectiveness beyond three to four weeks has not been demonstrated in controlled trials and that no body of evidence systematically addresses the appropriate duration of treatment.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 5, 7.5, 10, 15 and 30 mg, taken two or three times daily, and to be taken consistently either always with or always without food
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Buspirone hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Precautions (Drug Interactions, CYP3A4 inhibito… · a recorded source, not a stored snapshot
Sequenced Treatment Alternatives to Relieve Depression (STAR*D) registry record (NCT00021528) · a recorded source, not a stored snapshot
What we know
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Where a source records it acting
Brain: Moderate affinity for brain D2-dopamine receptors, as recorded in the label; the mechanism of action is stated as unknown
US prescribing information · 02628a0c-bfdb-4a58-8e48-bcd8ca12d53b · read 2026-08-27
Start
Buspirone
What a person takes: Oral tablet at 5, 7.5, 10, 15 and 30 mg, taken two or three times daily, and to be taken consistently either always with or always without food.
The measurement behind this step
Rapidly absorbed with extensive first-pass metabolism by CYP3A4; unchanged drug is about 1% of circulating radioactivity and peak concentrations after 20 mg are 1 to 6 ng/mL. Multiple-dose kinetics are non-linear. Food reduces presystemic clearance, raising AUC 84% and Cmax 116%, which is why the label asks for consistency rather than a particular choice. The principal metabolite 1-pyrimidinylpiperazine is itself pharmacologically active.
Getting in
Swallowed, and almost entirely destroyed on the way through
Nearly all of a dose is broken down before it reaches the bloodstream. Only about one per cent of what circulates is the drug itself.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Rapid absorption followed by extensive first-pass metabolism. In a radiolabelled study, unchanged buspirone accounted for about 1% of plasma radioactivity. Peak levels of 1 to 6 ng/mL appear 40 to 90 minutes after a 20 mg dose, and multiple-dose kinetics are non-linear, so repeated dosing gives higher levels than single-dose studies predict.
Buspirone hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Precautions (Drug Interactions, CYP3A4 inhibito… · a recorded source, not a stored snapshot
What survives depends on your breakfast and your other prescriptions
Food nearly doubles the amount that gets through. Grapefruit juice raises it ninefold. A tuberculosis antibiotic cuts it by ninety per cent.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
CYP3A4 is the metabolising enzyme. Labelled interaction studies span an 89.6% AUC reduction with rifampin to increases of 9.2-fold with grapefruit juice, 19-fold with itraconazole and up to 50-fold with nefazodone. Food alone raises AUC 84% and Cmax 116% by reducing presystemic clearance.
Buspirone hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Precautions (Drug Interactions, CYP3A4 inhibito… · a recorded source, not a stored snapshot
It binds a serotonin receptor, and not the benzodiazepine one
It sits on a particular serotonin receptor. It does not go near the receptor that Valium and its relatives use — which is why it does not sedate and is not habit-forming.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
High in vitro affinity for 5-HT1A receptors and moderate affinity for brain D2 receptors. No significant affinity for benzodiazepine receptors and no effect on GABA binding in vitro or in vivo. No anticonvulsant or muscle relaxant effect and no prominent sedation.
Buspirone hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Precautions (Drug Interactions, CYP3A4 inhibito… · a recorded source, not a stored snapshot
What happens after the receptor is bound is not stated. The prescribing information’s first sentence on pharmacology is that the mechanism of action is unknown.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The label reports binding affinity without intrinsic activity, so it does not distinguish agonism from antagonism, or presynaptic autoreceptor from postsynaptic receptor. It adds only that some studies suggest indirect effects on other neurotransmitter systems. The principal metabolite, 1-pyrimidinylpiperazine, is itself active and is present at far higher concentrations than the parent.
Buspirone hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Precautions (Drug Interactions, CYP3A4 inhibito… · a recorded source, not a stored snapshot
It is not a tablet you take when anxiety strikes. It works over weeks, and about four to five people need treating for one extra person to improve.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Number needed to treat of 4.4 (95% CI 2.16 to 15.4) on the Clinical Global Impression scale across 36 trials and 5,908 participants. Azapirones may be less effective than benzodiazepines, and it could not be determined whether they beat antidepressants, kava or psychotherapy.
Buspirone hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Precautions (Drug Interactions, CYP3A4 inhibito… · a recorded source, not a stored snapshot
The label says effectiveness beyond three to four weeks has not been demonstrated in controlled trials. Anxiety disorders last years.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Trial durations in the Cochrane review ran four to nine weeks with a single 14-week study. The only long exposure data on the label is a tolerability study of 264 patients treated for one year "without ill effect", which establishes safety over that period and says nothing about whether the drug was still working.
Buspirone hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Precautions (Drug Interactions, CYP3A4 inhibito… · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults with generalized anxiety disorder, particularly those who have not previously taken a benzodiazepine — the Cochrane review found the class useful "particularly for those participants who had not been on a benzodiazepine". It is contraindicated with monoamine oxidase inhibitors.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and effectiveness of buspirone were evaluated in two placebo-controlled 6 week trials involving a total of 559 pediatric patients (ranging from 6 to 17 years of age) with GAD.”
US prescribing information · 9a702362-39cb-4171-8d64-f37fa7e1f638 · read 2026-08-30
On older people, the label states: “In one study of 6632 patients who received buspirone for the treatment of anxiety, 605 patients were ≥ 65 years old and 41 were ≥ 75 years old; the safety and efficacy profiles for these 605 elderly patients (mean age = 70.8 years) were similar to those in the younger population (mean age = 43.3 years).”
US prescribing information · 9a702362-39cb-4171-8d64-f37fa7e1f638 · read 2026-08-30
On people who are pregnant, the label states: “Teratogenic Effects Pregnancy Category B No fertility impairment or fetal damage was observed in reproduction studies performed in rats and rabbits at buspirone doses of approximately 30 times the maximum recommended human dose.”
US prescribing information · 9a702362-39cb-4171-8d64-f37fa7e1f638 · read 2026-08-30
On people who are breastfeeding, the label states: “The extent of the excretion in human milk of buspirone or its metabolites is not known.”
US prescribing information · 9a702362-39cb-4171-8d64-f37fa7e1f638 · read 2026-08-30
Where the result stopped carrying
Effectiveness beyond three to four weeks has never been demonstrated in a controlled trial, per the label
The Cochrane review found azapirones may be less effective than benzodiazepines and could not establish superiority over antidepressants, kava or psychotherapy
The benefit was particularly evident in people who had not previously taken a benzodiazepine — not the population it is usually reached for
In STAR*D it tied with bupropion on remission and lost on every secondary outcome, including a 20.6% intolerance dropout rate
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablet at 5, 7.5, 10, 15 and 30 mg, taken two or three times daily, and to be taken consistently either always with or always without food
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Rapidly absorbed with extensive first-pass metabolism by CYP3A4; unchanged drug is about 1% of circulating radioactivity and peak concentrations after 20 mg are 1 to 6 ng/mL. Multiple-dose kinetics are non-linear. Food reduces presystemic clearance, raising AUC 84% and Cmax 116%, which is why the label asks for consistency rather than a particular choice. The principal metabolite 1-pyrimidinylpiperazine is itself pharmacologically active.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
No boxed warning. Not a controlled substance and no dependence liability. Contraindicated with monoamine oxidase inhibitors and within 14 days of stopping one, in either direction, because of serotonin syndrome and hypertension risk, and with reversible MAOIs such as linezolid and intravenous methylene blue. No cross-tolerance with benzodiazepines, so it will not block sedative-hypnotic withdrawal, and prior CNS depressants should be tapered before starting. Dizziness, nausea, headache, nervousness and lightheadedness are the common reactions. Patients are advised not to drive until they know how it affects them, to avoid large amounts of grapefruit juice, and to be cautious with alcohol despite the absence of a demonstrated interaction on motor and mental performance.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
Buspirone hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Precautions (Drug Interactions, CYP3A4 inhibito… · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet at 5, 7.5, 10, 15 and 30 mg, taken two or three times daily, and to be taken consistently either always with or always without food
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Multiple-dose kinetics are non-linear. Food reduces presystemic clearance, raising AUC 84% and Cmax 116%, which is why the label asks for consistency rather than a particular choice. The principal metabolite 1-pyrimidinylpiperazine is itself pharmacologically active.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
292 products list this as an active ingredient in the United States drug directory. 292 of them contain it and nothing else.
FDA National Drug Code directory · 71610-203 · read 2026-08-29
They are sold as capsule, powder and tablet, taken oral.
FDA National Drug Code directory · 71610-203 · read 2026-08-29
169 published labels name it as an active ingredient. 169 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 05c006d2-44b9-431f-bce2-aff09c043ecb · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 05c006d2-44b9-431f-bce2-aff09c043ecb · read 2026-08-29
Buspirone Hydrochloride is tablets at 5 mg, 7.5 mg, 10 mg, 15 mg, and 30 mg, recorded as prescription product; fda label in effect 2019-05-03 in the United States.
US prescribing information · 02628a0c-bfdb-4a58-8e48-bcd8ca12d53b · read 2026-08-27
Recorded price in US: 0.02175–0.11865 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 130 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Buspirone studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That 5-HT1A partial agonism is the mechanism — the label reports affinity, not intrinsic activity, and calls the mechanism unknown
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That efficacy demonstrated over three to four weeks persists across the months and years a chronic anxiety disorder lasts
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the one-year tolerability study in 264 patients says anything about continued effectiveness; it reports no efficacy outcome
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That buspirone can substitute for a benzodiazepine being withdrawn, which the label states it cannot because there is no cross-tolerance
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Buspirone are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
Six words: "The mechanism of action of buspirone is unknown"
In plain words
That is the opening sentence of the drug’s pharmacology section. Everything after it is a list of what buspirone binds and, more pointedly, what it does not.
What was measured
That 5-HT1A partial agonism is the mechanism of buspirone’s anxiolytic effect — an account absent from the label, which reports affinity without intrinsic activity and declares the mechanism unknown
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The clinical pharmacology section opens: "The mechanism of action of buspirone is unknown." It then establishes the drug by negation — no anticonvulsant effect, no muscle relaxant effect, no prominent sedation, no significant affinity for benzodiazepine receptors, no effect on GABA binding in vitro or in vivo — before offering high in vitro affinity for 5-HT1A receptors and moderate affinity for brain D2 receptors, and noting that some studies suggest indirect effects on other neurotransmitter systems. The textbook account, that buspirone is a partial agonist at postsynaptic 5-HT1A receptors and a fuller agonist at presynaptic autoreceptors, appears nowhere on the document; binding affinity is reported, intrinsic activity is not. Two further facts make the gap larger than it looks. Unchanged buspirone accounts for only about 1% of circulating radioactivity, so most of what a patient carries is metabolites, one of which — 1-pyrimidinylpiperazine — is pharmacologically active. And the effect takes weeks to appear, which no receptor-occupancy account explains on its own. The label records the uncertainty together with receptor-binding observations, without assigning an intrinsic activity it does not state.
Source
Buspirone hydrochloride United States prescribing information, Clinical Pharmacology section
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
A chronic condition, and no efficacy shown past four weeks
In plain words
Generalised anxiety disorder lasts years. Buspirone’s label states that its effectiveness beyond three to four weeks has not been demonstrated in controlled trials, and that no body of evidence addresses how long treatment should last.
What was measured
Longest duration over which controlled efficacy has been demonstrated, against the chronicity of the licensed condition
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The indications section reads: "The effectiveness of buspirone hydrochloride tablets in long-term use, that is, for more than 3 to 4 weeks, has not been demonstrated in controlled trials. There is no body of evidence available that systematically addresses the appropriate duration of treatment for GAD. However, in a study of long-term use, 264 patients were treated with buspirone hydrochloride tablets for 1 year without ill effect. Therefore, the physician who elects to use buspirone hydrochloride tablets for extended periods should periodically reassess the usefulness of the drug for the individual patient." The 264-patient study establishes tolerability over a year, not efficacy. The Cochrane review reaches the same point from the literature side: of 36 trials, study length ranged from four to nine weeks with a single 14-week study, and the authors concluded that "longer term studies are needed to show that azapirones are effective in treating GAD, which is a chronic long-term illness". This is a drug that takes two to four weeks to begin working and has never been shown to still be working at week five.
Written into the record, not signed off as a reviewed claim
Better than placebo across 36 trials, with a wide confidence interval
In plain words
Pooling 36 trials in 5,908 people, about four to five patients had to be treated for one extra person to improve on a global clinical scale. The confidence interval on that number ran from 2 to 15.
What was measured
Number needed to treat on the Clinical Global Impression scale, azapirones against placebo, across 36 trials and 5,908 participants
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Cochrane review of azapirones for generalized anxiety disorder included 36 trials reporting on 5,908 participants randomly allocated to azapirones and/or placebo, benzodiazepines, antidepressants, psychotherapy or kava. Azapirones, including buspirone, were superior to placebo, with a calculated number needed to treat on the Clinical Global Impression scale of 4.4 (95% CI 2.16 to 15.4). Azapirones may be less effective than benzodiazepines, and the review was unable to conclude whether they were superior to antidepressants, kava or psychotherapy. Azapirones appeared well tolerated and side effects were mild and non-serious, but fewer participants stopped taking benzodiazepines than azapirones — an acceptability finding that runs against the drug. A number needed to treat whose upper bound is 15.4 is compatible with a useful effect and with a marginal one, and the review does not narrow it further.
Written into the record, not signed off as a reviewed claim
It works best in the people least likely to be offered it
In plain words
The Cochrane review found azapirones useful "particularly for those participants who had not been on a benzodiazepine". In practice buspirone is most often reached for precisely because someone wants to avoid or come off a benzodiazepine.
What was measured
Effect modification by prior benzodiazepine exposure, and the labelled absence of cross-tolerance
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The review’s conclusion reads: "Azapirones appeared to be useful in the treatment of GAD, particularly for those participants who had not been on a benzodiazepine." The label supplies the pharmacological reason and a second, separate problem: because buspirone does not exhibit cross-tolerance with benzodiazepines and other common sedative-hypnotics, it will not block the withdrawal syndrome seen when those drugs are stopped, and the label therefore advises withdrawing a patient gradually from the prior drug before starting buspirone rather than swapping one for the other. So the two commonest clinical situations in which buspirone is chosen — a patient already on a benzodiazepine, and a patient coming off one — are the situation where the evidence is weakest and the situation the label warns it cannot cover. Buspirone’s lack of sedation, which is its principal selling point, is also the most likely explanation for the prior-benzodiazepine effect: someone who knows what a benzodiazepine feels like has a reference point against which buspirone feels like nothing.
Written into the record, not signed off as a reviewed claim
A blood level that moves five-hundredfold on what else you take
In plain words
Grapefruit juice raises the amount of buspirone in your blood ninefold. An antifungal raises it nineteenfold. One antidepressant raised it up to fiftyfold. An antibiotic for tuberculosis cuts it by ninety per cent.
What was measured
Fold change in buspirone Cmax and AUC across the labelled CYP3A4 inhibitor and inducer studies
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
All figures are from healthy-volunteer studies on the label. Buspirone is metabolised by CYP3A4 and undergoes extensive first-pass metabolism: unchanged drug is about 1% of circulating radioactivity and peak levels after a 20 mg dose are 1 to 6 ng/mL. Against that low and variable baseline, the labelled interactions are: itraconazole 200 mg/day for 4 days, 13-fold Cmax and 19-fold AUC increase; nefazodone 250 mg twice daily, increases up to 20-fold in Cmax and up to 50-fold in AUC, with a roughly 50% fall in the active metabolite 1-PP; grapefruit juice 200 mL double-strength three times daily for 2 days, 4.3-fold Cmax and 9.2-fold AUC; erythromycin 1.5 g/day for 4 days, 5-fold Cmax and 6-fold AUC; diltiazem 60 mg three times daily, 5.5-fold AUC and 4-fold Cmax; verapamil 80 mg three times daily, 3.4-fold; and rifampin 600 mg/day for 5 days, an 83.7% fall in Cmax and 89.6% fall in AUC with loss of pharmacodynamic effect. Food alone raises AUC 84% and Cmax 116%. From the rifampin floor to the nefazodone ceiling is a span of roughly five hundredfold in exposure, which is why the label instructs patients to take the drug consistently with or without food and to avoid large amounts of grapefruit juice, and recommends starting at 2.5 mg with the strong inhibitors.
Source
Buspirone hydrochloride United States prescribing information, Clinical Pharmacology and Precautions — Drug Interactions, Inhibitors and Inducers of Cytochrome P450 3A4
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
STAR*D: as good as bupropion at remission, and harder to stay on
In plain words
When citalopram had not worked, adding buspirone produced remission in 30.1% of patients and adding bupropion in 29.7% — effectively identical. But 20.6% dropped out of the buspirone arm for intolerance against 12.5% for bupropion.
What was measured
Remission on the 17-item Hamilton scale and dropout due to intolerance, buspirone against bupropion augmentation, in 851 patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
STAR*D level 2 (NCT00021528) randomly assigned 565 adult outpatients with non-psychotic major depressive disorder who had not remitted despite a mean of 11.9 weeks of citalopram (mean final dose 55 mg/day) to augmentation with sustained-release bupropion up to 400 mg/day, and 286 to augmentation with buspirone up to 60 mg/day. Remission on the 17-item Hamilton scale, rated by telephone by blinded raters, was 29.7% with bupropion and 30.1% with buspirone; QIDS-SR-16 remission was 39.0% and 32.9%, and response 31.8% and 26.9%. Bupropion produced a greater reduction in QIDS-SR-16 score (25.3% against 17.1%, p<0.04), a lower final score (8.0 against 9.1, p<0.02) and a lower dropout rate due to intolerance (12.5% against 20.6%, p<0.009). There was no placebo arm, so neither augmentation can be read as beating no augmentation — and buspirone has no antidepressant indication. The two arms tie on the primary outcome and separate on everything secondary, all of it against buspirone.
Written into the record, not signed off as a reviewed claim
The dopamine receptor nobody talks about
In plain words
The label records moderate affinity for brain dopamine D2 receptors and raises the question of what that might mean over time. Nothing on the document resolves it.
What was measured
Labelled D2 receptor affinity and the duration of the longest reported exposure study
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The pharmacology section states buspirone has moderate affinity for brain D2-dopamine receptors, and the precautions section opens a subsection headed "Possible Concerns Related to Buspirone’s Binding to Dopamine Receptors". That concern is not idle: the drugs that block D2 receptors for long periods are the antipsychotics, and their characteristic long-term harm is tardive dyskinesia. Buspirone’s D2 affinity is moderate rather than high and no such syndrome has been established for it. What has also never been established, for the same reason as everything else on this page, is what happens after four weeks — the point at which controlled efficacy data run out and at which any receptor-adaptation effect would begin to accumulate. The 264-patient year-long tolerability study is the only long exposure data the label offers, and it was not designed to detect a movement disorder.
Source
Buspirone hydrochloride United States prescribing information, Clinical Pharmacology and Precautions — Possible Concerns Related to Buspirone’s Binding to Dopamine Receptors
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
How many documents were read
169 documents were read for this substance.
RNAWiki source record
169 of them state the same proteinBinding, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
207LT9J9OC
CAS registry number
36505-84-7
PubChem compound
2477
RxNorm concept
1827
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Identity resolved
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Every public sentence names a source
The opening statement carries the origin: Written into the record, not signed off.
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Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
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Safety mode resolved
No register row and no identity class settled the question.
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Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
24 approved applications cover products containing this substance. The earliest was NDA018731, approved 19860929 to BRISTOL MYERS SQUIBB.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A 5-HT1A-binding anxiolytic with no benzodiazepine receptor affinity and no dependence liability, whose label opens by stating the mechanism of action is unknown and separately states that effectiveness beyond three to four weeks has not been demonstrated in controlled trials — and whose plasma exposure spans roughly a five-hundred-fold range across labelled interactions, from an 89.6% fall with rifampin to a 50-fold rise with nefazodone.
Recorded evidence blocks (10)
Q1
On the Buspirone label: indicated for what?
"Buspirone hydrochloride tablets, USP are indicated for the management of anxiety disorders or the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.": indications and usage on Buspirone's label. DailyMed label · 801803eb-be17-4064-8813-7ccf52316cde · 2026-08-01
Q2
59 registered trials of Buspirone — at which phases?
"Patient recruitment and Funding inadequate to finish trial"; 6 of 59 registered studies
Show the evidence
Trial
NCT00746954
terminated; "Patient recruitment and Funding inadequate to finish trial"
NCT01395953
withdrawn; "This study was withdrawn due to competing research interests and slow recruitment."
NCT01833312
terminated; "Slow recruitment, cessation of funding"
NCT02483598
terminated; "Initial analysis of results warranted a study re-design and work on the study was suspended."
NCT02589340
terminated; "Low enrollment"
NCT03432065
withdrawn; "This study was withdrawn due to competing research interests and slow recruitment."
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Buspirone used BCI-024: over-encapsulated Buspirone tablet 15 mg QD and BCI-049: over-encapsulated Melatonin tablet 3 mg QD — over how long?
Human studies of Buspirone used "BCI-024: over-encapsulated Buspirone tablet 15 mg QD and BCI-049: over-encapsulated Melatonin tablet 3 mg QD". ClinicalTrials.gov · 2026-09-01
8 recorded entries; human; tablet; also "BUSPAR® 30 mg Tablet", "Buspirone Hydrochloride 30 mg Tablet", "Buspirone 10 Mg Oral Tablet"
2 to 3 hours; The average elimination half-life of unchanged buspirone after single doses of 10 mg to 40 mg is about 2 to 3 hours.
bioavailabilityclinical_pharmacology
90 %; The single-dose bioavailability of unchanged buspirone when taken as a tablet is on the average about 90% of an equivalent dose of solution, but there is large variability.
metabolismclinical_pharmacology
Buspirone hydrochloride tablets are rapidly absorbed in man and undergo extensive first-pass metabolism.
recorded 2026-08-01 · last checked 2026-09-04
Q6
Which 22 trials of Buspirone posted no result?
Posted no result
22 of 22 completed trials
Registrations
NCT00652730, NCT00653419, NCT00840398, NCT00840606, NCT00326235 and NCT00166621, and 16 more
Completion dates
oldest 1998-09; newest 2023-10-04
Show the evidence
Trial
NCT00652730
1998-09
NCT00653419
1998-09
NCT00840398
2001-12
NCT00840606
2002-04
NCT00326235
2004-07
NCT00166621
2005-08
14 further recorded trials
NCT00174226
2006-01
NCT00021528
2006-09
NCT00334360
2007-08
NCT00149617
2007-12
NCT00360191
2007-12
NCT04352686
2012-11
NCT01743235
2013-06
NCT01699828
2014-06
NCT00873509
2015-01
NCT03444831
2017-04-01
NCT03521960
2020-06-30
NCT05377619
2022-03-06
NCT05430217
2022-05-09
NCT02617017
2023-03-23
Q7
At the median, Buspirone's trials enrolled 34 people — anything larger?
Median enrolment
34
Largest enrolment
4000
Registered trials counted
58
Q8
What do 442 spontaneous reports say about Buspirone — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Buspirone appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 442 reaction mentions were counted: drug hypersensitivity 103; anxiety 55; serotonin syndrome 43; dizziness 42. FAERS via Open Targets · CHEMBL1200399 · 2026-06-24
Show the evidence
drug hypersensitivity
103
anxiety
55
serotonin syndrome
43
dizziness
42
drug interaction
41
tremor
41
4 more recorded rows
confusional state
33
suicide attempt
29
depression
28
agitation
27
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Buspirone's label not list?
Nefazodone (See Inhibitors and Inducers of Cytochrome P450 3A4 (CYP3A4) ) Trazodone There is one report suggesting that the concomitant use of trazodone hydrochloride and buspirone may have caused 3 to 6-fold elevations on SGPT (ALT) in a few patients.
drug_interactions
Inhibitors and Inducers of Cytochrome P450 3A4 (CYP3A4) Buspirone has been shown in vitro to be metabolized by CYP3A4.
drug_interactions
Other Inhibitors and Inducers of CYP3A4 Substances that inhibit CYP3A4, such as ketoconazole or ritonavir, may inhibit buspirone metabolism and increase plasma concentrations of buspirone while substances that induce CYP3A4, such as dexamethasone or certain anticonvulsants (phenytoin, phenobarbital, carbamazepine), may increase the rate of buspirone metabolism.
drug_interactions
Consequently, when administered with a potent inhibitor of CYP3A4, a low dose of buspirone used cautiously is recommended.
drug_interactions
When used in combination with a potent inducer of CYP3A4 the dosage of buspirone may need adjusting to maintain anxiolytic effect.
clinical_pharmacology
Buspirone is metabolized primarily by oxidation, which in vitro has been shown to be mediated by cytochrome P450 3A4 (CYP3A4) (see PRECAUTIONS, Drug Interactions ).
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 6 source rows
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