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Paroxetine

  • Prescription medicine
  • Prescription only
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What Paroxetine does in the body

Paroxetine blocks the transporter that recycles serotonin out of the gap between nerve cells, so serotonin stays there longer.

Its label says the mechanism of benefit is unknown and only presumed to follow from that. Two other features define it in practice: it strongly blocks a liver enzyme called CYP2D6, which changes the levels of many other drugs, and it partly blocks the enzyme that clears itself, so doubling the dose raises the blood level by much more than double.

Why people take it. Depression, obsessive-compulsive disorder, panic, social anxiety, generalised anxiety and post-traumatic stress; separately, at a much lower dose, menopausal hot flushes

What happened in people

24%, 54% and 91% increases in breast cancer death for 25%, 50% and 75% absolute increases in paroxetine-tamoxifen overlap among 2,430 women

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.

The limit that matters most

That paroxetine is effective and well tolerated in adolescent depression — the 2001 conclusion, contradicted by the restored data set and by the current label

Where it acts
Serotonin transporter on presynaptic terminals in the central nervous system; the interaction that matters most outside the brain is at hepatic CYP2D6
Kind of result
Living longer, or avoiding a major event
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.

What the registries record it as

  • Its recorded molecular formula is C19H20FNO3•HCl, weighing 374.8.

    US prescribing information · 7d558598-6905-46da-8f34-668456c68411 · read 2026-08-30

Where each sentence above came from

A person wrote this explanation into the record, with the studies named in the path below.

The recorded use, written for a reader without medical training. Not signed off.

A limit recorded against this substance. Not signed off as a reviewed claim.

The four opening statements run to 123 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.

Stand-in result

A stand-in result is a number measured because the real result takes too long.

A picture of it, and where the picture fails

It is like judging a journey by the speedometer rather than by arriving.

Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.

What people get wrong. A stand-in result is often reported as the result itself.

A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.

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.

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.

Pathway

A pathway is a chain of steps inside a cell, each one setting off the next.

A picture of it, and where the picture fails

A pathway is like a row of dominoes.

Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.

What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.

An ordered series of molecular interactions producing a defined cellular change.

What happened in peopleRead from sources, not yet reviewed

What was measured, goal by goal

One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.

Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.

There is no single score. A strong test result and a weak life result are different facts.

Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
GoalLife outcomeWhat a body can doHow a person feelsA test resultA step in the bodyHarmsHow longWho was studied
MoodNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Waiting for a reviewer15 registered symptom measure.Nothing in the sources checkedNo registered study lists a test result for this goal.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
Fertility and sexual healthNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Waiting for a reviewer1 registered symptom measure.Only a number moved1 registered test measure.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
PainNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Waiting for a reviewer1 registered symptom measure.Nothing in the sources checkedNo registered study lists a test result for this goal.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Mood
hamilton depression rating scale; hamilton depression scale; liebowitz social anxiety scale; hamilton depression rating scale scores; hamilton anxiety scale total; depressive symptom scores; hamilton anxiety rating scale; changes in cornell s depression scale
Fertility and sexual health
sperm concentration; sperm motility; sperm morphology; changes in sexual functioning questionnaire total
Pain
pain levels

Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.

What each mark on this table means
Nothing in the sources checked
No registered study lists a life outcome for this goal.
Waiting for a reviewer
15 registered symptom measure.
Not recorded
Harms were not a registered measure for this goal.
Only a number moved
1 registered test measure.

What happened in peopleRead 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.

Change from baseline to end of the eight-week acute phase in total Hamilton depression score, and the proportion of responders, in adolescents with unipolar major depression

The study did not show it

Who was studied
Study 329, as restored under the RIAT protocol (BMJ 2015;351:h4320)
How many people
275
Study design
Phase 3, randomised, double-blind, placebo-controlled, three-arm
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Least-squares mean Hamilton reduction 10.7 (95% CI 9.1 to 12.3) on paroxetine, 9.0 (7.4 to 10.5) on imipramine and 9.1 (7.5 to 10.7) on placebo, p=0.20; no prespecified primary or secondary outcome differed statistically or clinically from placebo
Repeated elsewhere
Failed to Replicate

What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.

The limits of this study, and where it came from

Main limit. Clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events on paroxetine and cardiovascular problems on imipramine. No adverse-event coding dictionary had been prespecified. The 2001 publication of this trial reported it as showing efficacy and good tolerability, and has not been retracted.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral tablet at 10, 20, 30 and 40 mg, controlled-release tablet, oral suspension, and a separate 7.5 mg mesylate capsule licensed only for menopausal vasomotor symptoms

Interval reported. 95% CI 9

Written into the record, not signed off as a reviewed claim.

Efficacy in paediatric major depressive disorder, as summarised in the label’s Pediatric Use section

The study did not show it

Who was studied
Three paediatric major depressive disorder trials (NDA 020031, section 8.4)
How many people
752
Study design
Randomised, double-blind, placebo-controlled
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
The label states effectiveness was not demonstrated in three placebo-controlled trials in 752 paroxetine-treated paediatric patients with MDD
Repeated elsewhere
Failed to Replicate

What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.

The limits of this study, and where it came from

Main limit. Emotional lability including self-harm, suicidal thoughts, attempted suicide, crying and mood fluctuations; hostility; decreased appetite; tremor; sweating; hyperkinesia; and agitation each occurred in at least 2% of paediatric patients at a rate at least twice that on placebo. 752 is the number treated, not the number randomised, which the label does not state.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral tablet at 10, 20, 30 and 40 mg, controlled-release tablet, oral suspension, and a separate 7.5 mg mesylate capsule licensed only for menopausal vasomotor symptoms

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

Co-primary reduction from baseline in frequency and in severity of moderate to severe vasomotor symptoms at weeks 4 and 12, in postmenopausal women with at least seven to eight episodes daily at baseline

The study showed what it set out to show

Who was studied
Brisdelle Phase 3 vasomotor symptom trials 1 and 2 (NDA 204516, section 14, Tables 4 and 5)
How many people
1174
Study design
Phase 3, randomised, double-blind, placebo-controlled
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Trial 1 (n=606): median daily frequency change -4.3 against -3.1 at week 4 and -5.9 against -5.0 at week 12, treatment differences of 1.2 and 0.9 episodes per day from a baseline median of 10.4, p<0.01 for both
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. In Trial 1 the severity difference at week 12 was 0.04 and not statistically significant (p=0.17). The FDA’s Reproductive Health Drugs Advisory Committee voted 10 to 4 against recommending approval in March 2013; the agency approved the product on 28 June 2013.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral tablet at 10, 20, 30 and 40 mg, controlled-release tablet, oral suspension, and a separate 7.5 mg mesylate capsule licensed only for menopausal vasomotor symptoms

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

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 happened in peopleRead from sources, not yet reviewed

How close this is to real life

The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.

  1. Living longer, or avoiding a major event Evidence recorded. Death, a heart attack, a stroke, a hospital stay.1 registered measure of this kind. No reviewed result.
  2. What a body can do day to day No evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
  3. Measured performance No evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
  4. Symptoms and quality of life Evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.18 registered measures of this kind.
  5. A number that stands in for health Evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.2 registered measures of this kind.
  6. A step measured inside a person Evidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
  7. Animals Evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in C. elegans (roundworm), Mouse, Rat. A result in animals says what to test next. It does not say what happens in people.
  8. Cells in a dish Evidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
  9. A guess from software No evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.

Higher on these steps means closer to something a person would feel. It does not mean better done.

What it changes in the bodyRead 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.

  1. Start

    Paroxetine

    What a person takes: Oral tablet at 10, 20, 30 and 40 mg, controlled-release tablet, oral suspension, and a separate 7.5 mg mesylate capsule licensed only for menopausal vasomotor symptoms.

    The measurement behind this step

    Completely absorbed after oral dosing of the hydrochloride solution. Steady state is reached in about 10 days for most subjects but substantially longer in some, and exposure is non-linear because one metabolising enzyme is readily saturable: at 30 mg daily, steady-state mean Cmax was 61.7 ng/mL, Cmin 30.7 ng/mL, Tmax 5.2 hours and half-life 21 hours. Food raises Cmax by about 29% and shortens Tmax without materially changing AUC.

  2. Getting in

    One isomer of four, in a specific crystal form

    Unlike most of its class, paroxetine is a single mirror-image form rather than a mixture — and the exact crystal it is packed as changes how it dissolves.

    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

    The (3S,4R)-trans isomer of a 4-(4-fluorophenyl)piperidine bearing a sesamol ether at carbon 3. Marketed as the hydrochloride hemihydrate, the hydrochloride anhydrate and the mesylate; the differences between hydrochloride polymorphs were the subject of extended patent litigation. Food raises Cmax by about 29% and shortens time to peak from 6.4 to 4.9 hours while barely changing total exposure.

  3. Reaching the cell

    It jams the enzyme that clears it

    The liver enzyme that removes paroxetine is also blocked by paroxetine. Doubling the dose raises the blood level by much more than double, and halving it drops the level by much more than half.

    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

    One of the enzymes metabolising paroxetine is readily saturable, so its pharmacokinetics are non-linear. At steady state on 30 mg daily, mean Cmax was 61.7 ng/mL and mean half-life 21 hours, with steady-state Cmax and Cmin about 6 and 14 times single-dose predictions and AUC0-24 about 8 times. Steady state is reached in roughly 10 days for most subjects but substantially longer in some.

  4. What it acts on

    The serotonin transporter is blocked

    It plugs the pump that recycles serotonin, and it does so more potently than most of its class.

    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

    Potent and highly selective inhibition of neuronal serotonin reuptake with only very weak effects on noradrenaline and dopamine reuptake, demonstrated at clinically relevant doses by blockade of serotonin uptake into human platelets. Section 12.1 states the mechanism of therapeutic action across all six licensed indications is unknown and only presumed to follow from this.

  5. The change it makes

    And blocks CYP2D6 for every other drug too

    The same enzyme block that traps paroxetine also changes the levels of many unrelated drugs — including tamoxifen, which needs that enzyme to become active at all.

    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

    The label lists propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine and risperidone as CYP2D6 substrates whose exposure rises, and directs dose reduction where needed and an increase again if paroxetine is stopped. Tamoxifen is handled separately: concomitant use may reduce plasma endoxifen and tamoxifen efficacy, and the label directs considering an antidepressant with little or no CYP2D6 inhibition.

  6. What that does for a person

    In adults, a rating scale moves; in adolescents, it did not

    Adult trials across six conditions supported approval. Three paediatric depression trials in 752 treated patients did not.

    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

    Licensed adult efficacy rests on short placebo-controlled trials in each of six indications, and in the 2018 network meta-analysis paroxetine was one of seven drugs more effective than the others in head-to-head comparison (odds ratios 1.19 to 1.96). Section 8.4 states effectiveness was not demonstrated in three placebo-controlled paediatric trials in 752 treated patients, and the RIAT restoration of Study 329 found Hamilton reductions of 10.7 against 9.1 on placebo, p=0.20.

  7. What that does for a person

    Stopping is its own event

    Short half-life, no long-lived metabolite, and a blood level that falls faster than the dose does. The label lists seizures among the discontinuation reactions.

    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

    Labelled discontinuation reactions include nausea, sweating, dysphoric mood, irritability, agitation, dizziness, paraesthesia including electric-shock sensations, tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus and seizures, with gradual reduction directed whenever possible. In the GAD and PTSD trials, decreases of 10 mg/day at weekly intervals followed by a week at 20 mg/day were used before stopping.

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 it would be like to takeRead from sources, not yet reviewed

Felt, measured, or meaningful

Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.

Felt

Things a person could notice without a test.

  • hamilton depression rating scale
  • hamilton depression scale
  • liebowitz social anxiety scale
  • hamilton depression rating scale scores
  • hamilton anxiety scale total
  • depressive symptom scores
  • pain levels
  • hamilton anxiety rating scale
  • changes in neuropsychiatric inventory
  • changes in cornell s depression scale

and 8 more.

Measured

Things only a test, a scale or a device shows.

  • sperm concentration
  • cmax maximum observed concentration

Meaningful

Things that change how a life goes, not only a number.

  • probability of remission

A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.

Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.

Measured, but not felt. A number moves. The person notices nothing. Both can be true.

Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.

Matters, but takes years. The result that counts may take longer than anyone would keep watching.

Names that fit none of the three (19)
  • ham d 17
  • caps recurrent distressing dreams item
  • clinician administered ptsd scale
  • side effects
  • semen volume
  • sperm motility
  • sperm morphology
  • changes in updrs subscale
  • caps
  • bioequivalence
  • time of retention
  • 18fdg pet pdss ham a
  • total of the ham d 17 items
  • intravaginal ejaculatory latency time
  • hot flash severity at week 4 and week 12
  • adverse events all
  • incidence of adverse events
  • response rate
  • yale brown obsessive compulsive scale

These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.

What it would be like to takeRead from sources, not yet reviewed

How long anything takes

Nine different lengths of time that get confused with each other. None of them is worked out from another.

  1. Before anything is noticed. RNAWiki does not store this separately, and never works it out from another figure on this page.

  2. Before a test result moves. RNAWiki does not store this separately, and never works it out from another figure on this page.

  3. Before performance moves. RNAWiki does not store this separately, and never works it out from another figure on this page.

  4. How long the result was watched. No finished study window is recorded for a study that tested this substance.

  5. How long people took it. How long people actually took it is not stored. The study window is not the same thing.

  6. How long people were followed. Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.

  7. How fast the body clears it. 21 hours hours

    Read from the label, which states: “Elimination Metabolism The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days of paroxetine.”

  8. How long effects linger. RNAWiki does not store this separately, and never works it out from another figure on this page.

  9. Beyond the studies. Nothing is recorded about the long term.

    The longest finished study sets the edge of what anyone measured.

A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.

What is missing or unclearRead 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 across six psychiatric indications, and postmenopausal women at a tenth of the psychiatric dose for hot flushes. Not children or adolescents — the label states safety and effectiveness in paediatric patients have not been established. Women intending pregnancy or in the first trimester should start it only after other options have been considered.

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 paroxetine in pediatric patients have not been established [see Box Warning].”

    US prescribing information · 7d558598-6905-46da-8f34-668456c68411 · read 2026-08-30

  • On older people, the label states: “In premarketing clinical trials with paroxetine, 17% of patients treated with paroxetine (approximately 700) were 65 years of age or older.”

    US prescribing information · 7d558598-6905-46da-8f34-668456c68411 · read 2026-08-30

  • On people who are pregnant, the label states: “Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.5 ) and Clinical Considerations].”

    US prescribing information · 7d558598-6905-46da-8f34-668456c68411 · read 2026-08-30

  • On people who are breastfeeding, the label states: “Risk Summary Data from the published literature report the presence of paroxetine in human milk (see Data).”

    US prescribing information · 7d558598-6905-46da-8f34-668456c68411 · read 2026-08-30

Where the result stopped carrying

  • Three placebo-controlled paediatric depression trials failed to demonstrate effectiveness, and the label says so
  • Study 329’s published conclusion did not survive reanalysis of its own patient-level data, and the paper has not been retracted
  • The FDA’s own advisory committee voted 10 to 4 against the hot-flush indication before it was approved
  • The first-trimester cardiovascular malformation signal forced a label change that singles paroxetine out from the rest of its class
  • 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 takeRead 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 for a different goal

The studies measured something else entirely.

On this record: Some registered studies measured things that match no goal on this page.

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 (10)
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 takeRead 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 10, 20, 30 and 40 mg, controlled-release tablet, oral suspension, and a separate 7.5 mg mesylate capsule licensed only for menopausal vasomotor symptoms

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

Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Suppression classes recorded: S3, S6.

No source is stored against this line.

What is in the pack

Completely absorbed after oral dosing of the hydrochloride solution. 2 hours and half-life 21 hours. Food raises Cmax by about 29% and shortens Tmax without materially changing AUC.

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 takeRead 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

Boxed warning for suicidal thoughts and behaviours in children, adolescents and young adults, with safety and effectiveness in paediatric patients not established. Strong CYP2D6 inhibition, with tamoxifen singled out. Labelled discontinuation syndrome including electric-shock sensory disturbances and seizures, with gradual reduction directed. Seizures occurred in 0.1% of treated patients in clinical studies, from which people with a seizure history were excluded. First-trimester exposure is associated with a less than two-fold increase in cardiovascular malformations, and the class carries risks of persistent pulmonary hypertension of the newborn and poor neonatal adaptation, and of postpartum haemorrhage with exposure in the month before delivery.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

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 unclearRead 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 10, 20, 30 and 40 mg, controlled-release tablet, oral suspension, and a separate 7.5 mg mesylate capsule licensed only for menopausal vasomotor symptoms

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

2 hours and half-life 21 hours. Food raises Cmax by about 29% and shortens Tmax without materially changing AUC.

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

  • 196 products list this as an active ingredient in the United States drug directory. 196 of them contain it and nothing else.

    FDA National Drug Code directory · 72189-492 · read 2026-08-29

  • They are sold as capsule, powder, suspension, tablet, film coated and tablet, film coated, extended release, taken oral.

    FDA National Drug Code directory · 72189-492 · read 2026-08-29

  • The regulator's established pharmacologic class for it is serotonin reuptake inhibitor [epc] and serotonin uptake inhibitors [moa].

    FDA National Drug Code directory · 72189-492 · read 2026-08-29

  • 93 published labels name it as an active ingredient. 93 of them describe this substance alone, which is where its own label text on this page comes from.

    US prescribing information · 7d558598-6905-46da-8f34-668456c68411 · read 2026-08-29

  • Those labels are classed as human prescription drug.

    US prescribing information · 7d558598-6905-46da-8f34-668456c68411 · read 2026-08-29

  • Paroxetine is oral at 3 DOSAGE FORMS AND STRENGTHS Paroxetine tablets, USP are available as: • 10 mg: White to off-white, round-shaped, biconvex, film- coated tablets debossed with the logo of 'ZC, 15 and bisect' on one side and plain on oth…, recorded as fda label in effect 2026-08-12 in the United States.

    US prescribing information · 7d558598-6905-46da-8f34-668456c68411 · read 2026-08-30

  • Recorded price in US: 0.06211–2.63265 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 128 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

  • Recorded price in US: 1.40405 USD per one millilitre, for the one priced product, 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 takeRead 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.

Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.

Questions worth asking

  • Which of the trials of Paroxetine 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 unclearRead 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 paroxetine is effective and well tolerated in adolescent depression — the 2001 conclusion, contradicted by the restored data set and by the current label

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 one presumed serotonergic mechanism explains benefit across six unrelated psychiatric diagnoses, which the label offers as a presumption

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 a median difference of about one hot flush per day out of ten warranted a new branded product against a 10-to-4 advisory committee vote

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 CYP2D6 interaction is a class effect; the cohort that measured it found the excess mortality with paroxetine and not with the other antidepressants studied

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 unclearRead 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 Paroxetine 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 peopleRead 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.

Study 329: the same data, reanalysed, showed no efficacy and more harm
In plain words
A 2001 paper reported paroxetine as effective and well tolerated for adolescent depression. In 2015 an independent team obtained the full data set from the same trial and found no benefit on any prespecified outcome, and clinically significant increases in harm including suicidal ideation and behaviour. The original paper has never been retracted.
What was measured
Least-squares mean change in Hamilton depression score at eight weeks, paroxetine against placebo, in 275 adolescents
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Study 329 randomised 275 adolescents with major depression of at least eight weeks’ duration across 12 North American academic psychiatry centres between April 1994 and February 1998, to eight weeks of double-blind paroxetine 20 to 40 mg, imipramine 200 to 300 mg, or placebo. The prespecified primary efficacy variables were change in total Hamilton score and the proportion of responders at acute endpoint. Reanalysis under the Restoring Invisible and Abandoned Trials protocol found the efficacy of paroxetine and imipramine not statistically or clinically significantly different from placebo on any prespecified primary or secondary outcome: least-squares mean Hamilton reductions of 10.7 (95% CI 9.1 to 12.3), 9.0 (7.4 to 10.5) and 9.1 (7.5 to 10.7) points for paroxetine, imipramine and placebo respectively, p=0.20. There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group. The authors note that no coding dictionary for adverse events had been prespecified. Two of the reanalysis authors declare paid expert work for plaintiffs in litigation involving the manufacturer, which is disclosed in the paper and belongs on this page alongside the finding.
Source
Le Noury J, Nardo JM, Healy D, et al. Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. BMJ 2015;351:h4320
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
The label now says effectiveness was not demonstrated in 752 treated adolescents
In plain words
Whatever the 2001 paper said, the prescribing information is unambiguous. Three placebo-controlled trials in 752 paroxetine-treated children and adolescents with depression did not demonstrate effectiveness.
What was measured
Efficacy outcome of three placebo-controlled paediatric major depressive disorder trials, 752 treated patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Section 8.4 states: "The safety and effectiveness of paroxetine tablets in pediatric patients have not been established... Effectiveness was not demonstrated in three placebo-controlled trials in 752 paroxetine tablets-treated pediatric patients with MDD." The same section lists the adverse reactions occurring in at least 2% of paediatric patients at twice the placebo rate: emotional lability including self-harm, suicidal thoughts, attempted suicide, crying and mood fluctuations; hostility; decreased appetite; tremor; sweating; hyperkinesia; and agitation. It separately lists the reactions on discontinuation in the paediatric trials that included a taper — emotional lability including suicidal ideation and suicide attempt, nervousness, dizziness, nausea and abdominal pain. A negative efficacy finding and a positive harm finding in the same population, on the same document, is the strongest form this audit can take.
Source
Paroxetine United States prescribing information, section 8.4 Pediatric Use and Boxed Warning (NDA 020031)
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
Paroxetine with tamoxifen: 91% higher breast cancer death at high overlap
In plain words
Tamoxifen has to be switched on by a liver enzyme that paroxetine blocks harder than any other drug in its class. In 2,430 older Ontario women on tamoxifen and one antidepressant, more overlap with paroxetine meant more breast cancer deaths. No other antidepressant showed it.
What was measured
Adjusted risk of breast cancer death as a function of paroxetine-tamoxifen treatment overlap in 2,430 women
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A population-based cohort of women in Ontario aged 66 or over treated with tamoxifen for breast cancer between 1993 and 2005 who had overlapping treatment with a single SSRI. Of 2,430 such women, 374 (15.4%) died of breast cancer over a mean 2.38 years of follow-up. After adjustment for age, duration of tamoxifen treatment and other potential confounders, absolute increases of 25%, 50% and 75% in the proportion of tamoxifen treatment overlapping with paroxetine were associated with 24%, 54% and 91% increases in the risk of breast cancer death (p<0.05 for each). No such risk was seen with the other antidepressants. At the sample median overlap of 41%, the authors estimated one additional breast cancer death within five years of stopping tamoxifen for every 19.7 patients treated (95% CI 12.5 to 46.3). This is an observational study and confounding by indication cannot be excluded, but the drug-specific gradient and the known CYP2D6 mechanism point the same way, and the label now names tamoxifen and directs considering an antidepressant with little or no CYP2D6 inhibition.
Source
Kelly CM, Juurlink DN, Gomes T, et al. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ 2010;340:c693
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Approved for hot flushes over a 10-to-4 vote against, on one fewer flush a day
In plain words
The same molecule was re-approved in 2013 at a tenth of the psychiatric dose as a new branded product for menopausal hot flushes. An FDA advisory committee had voted 10 to 4 against. The measured difference from placebo was about one fewer hot flush a day out of ten.
What was measured
That a median difference of about one moderate-to-severe hot flush per day, from a baseline of ten, justified a new patent-protected product built on a generic molecule against the advice of the agency’s own advisory committee
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Brisdelle, paroxetine mesylate 7.5 mg, was approved on 28 June 2013 under NDA 204516 for moderate to severe vasomotor symptoms of menopause, with an explicit limitation of use stating it is not indicated for any psychiatric condition and that the lower dosage has not been established for one. Effectiveness rested on two Phase 3 placebo-controlled trials in 1,174 postmenopausal women who had at least seven to eight moderate-to-severe episodes a day at baseline. In Trial 1 (n=606), the median daily frequency fell 4.3 against 3.1 at week 4 and 5.9 against 5.0 at week 12, giving median treatment differences of 1.2 and 0.9 episodes per day from a baseline median of 10.4; the severity difference was 0.05 at week 4 (p<0.01) and 0.04 at week 12, where it was not statistically significant (p=0.17). The FDA’s Reproductive Health Drugs Advisory Committee voted 10 to 4 against recommending approval in March 2013, and the agency approved it anyway; FDA reviewers subsequently published their reasoning in a 2014 NEJM perspective. The pharmacological content of the product is a molecule that had been generic for a decade.
Source
BRISDELLE (paroxetine mesylate) United States prescribing information, sections 1 and 14, Tables 4 and 5 (NDA 204516); Orleans RJ, Li L, Kim MJ, et al. FDA approval of paroxetine for menopausal hot flushes. N Engl J Med 2014;370:1777-1779
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 first-trimester cardiac malformation signal that changed the label
In plain words
Paroxetine is the drug in its class singled out on pregnancy grounds. Its label states an association with a less than two-fold increase in cardiovascular malformations after first-trimester exposure, and directs that it be started in women who might become pregnant only after other options have been considered.
What was measured
Labelled magnitude of the first-trimester cardiovascular malformation association and the resulting initiation restriction
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Section 8.1 states that paroxetine is associated with a less than two-fold increase in cardiovascular malformations when administered during the first trimester, that individual epidemiological studies have reported inconsistent findings but some meta-analyses have identified an increased risk, and that for women who intend to become pregnant or who are in their first trimester paroxetine should be initiated only after consideration of the other available treatment options. It records animal data in which no treatment-related malformations were seen at up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits during organogenesis, but in which dosing through the last trimester and lactation increased pup deaths in the first four days of lactation at 1 mg/kg/day, below the maximum recommended human dose on a body-surface basis. The section also records class risks of persistent pulmonary hypertension of the newborn and poor neonatal adaptation, and states that women who stop antidepressants in pregnancy are more likely to relapse. The label sets out both sides and does not rank them, which is honest and leaves the decision unresolved.
Source
Paroxetine United States prescribing information, section 8.1 Pregnancy (NDA 020031)
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
Effective in adults by the largest comparison ever run, and hard to stop
In plain words
In the network meta-analysis of 21 antidepressants across 522 trials, paroxetine was one of seven drugs that beat the others when compared head to head. Its own label separately describes a discontinuation syndrome that includes seizures.
What was measured
Head-to-head efficacy odds ratios in 522 trials, against labelled steady-state half-life and discontinuation reactions
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the head-to-head studies of the 2018 network meta-analysis, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine and vortioxetine were more effective than the other antidepressants, with odds ratios ranging from 1.19 to 1.96; certainty of evidence across the analysis was rated moderate to very low and 9% of trials were at high risk of bias. Against that, paroxetine has a steady-state half-life of 21 hours, no long-lived active metabolite, and saturable metabolism that makes steady-state Cmax and Cmin about 6 and 14 times what single-dose data predict — the pharmacological basis for its reputation as the hardest of the class to stop. The labelled discontinuation reactions run from nausea, dizziness and electric-shock sensory disturbances through emotional lability and hypomania to seizures, and the label directs gradual reduction whenever possible. Both facts are measured; they belong on the same page because a drug that works and is hard to leave is a different proposition from one that only works.
Source
Cipriani A, Furukawa TA, Salanti G, et al. Lancet 2018;391:1357-1366; paroxetine United States prescribing information, sections 5.7 and 12.3 (NDA 020031)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Six indications, one hypothesis, no mechanism
In plain words
Paroxetine is licensed for depression, obsessive-compulsive disorder, panic, social anxiety, generalised anxiety and post-traumatic stress. Its label says the mechanism in all six is unknown, and presumed to be the same one.
What was measured
That one serotonergic mechanism explains benefit across six unrelated psychiatric diagnoses — a presumption the label states as such and that no biological measurement supports
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 12.1 reads: "The mechanism of action of paroxetine tablets in the treatment of MDD, SAD, OCD, PD, GAD, and PTSD is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin." One presumed mechanism is offered for six conditions that share no diagnostic test, no biomarker and no agreed pathophysiology. The 2022 umbrella review of the serotonin theory synthesised 17 systematic reviews, meta-analyses and large data-set analyses across serotonin and 5-HIAA concentrations, receptor and transporter binding, tryptophan depletion and transporter genetics, and found no consistent evidence that depression is associated with lowered serotonin. Nothing about that finding removes the licensed efficacy in adults; it removes the explanation that has been attached to it.
Source
Paroxetine United States prescribing information, sections 12.1 and 12.2 (NDA 020031); Moncrieff J et al., Mol Psychiatry 2023;28:3243-3256
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

How many documents were read

  • 92 documents were read for this substance.

    RNAWiki source record

  • 2 of them state the same tMax, and they agree.

    RNAWiki source record

Checks this page had to pass

  • Passed

    Identity resolved

    no open identity hold

  • Passed

    No unresolved merge across substance families

    no quarantine open

  • Passed

    Every public sentence names a source

    The opening statement carries the origin: Written into the record, not signed off.

  • Not passed

    Trial roles classified for highlighted evidence

    No registered study is classified as testing this substance.

  • Passed

    No internal keys in reader text

    enforced by the copy-contract test over the rendered page

  • Passed

    Safety mode resolved

    Suppression classes recorded: S3, S6.

  • Passed

    Canonical metadata present

    slug and display name present

What is missing or unclearRead 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

  • 35 approved applications cover products containing this substance. The earliest was NDA020031, approved 19921229 to APOTEX.

    Drugs@FDA application register · NDA020031 · read 2026-08-29

  • Marketing status on the register: discontinued and prescription.

    Drugs@FDA application register · NDA020031 · read 2026-08-29

  • The earliest marketing start date recorded for a listed product is 20030730.

    FDA National Drug Code directory · 72189-492 · read 2026-08-29

What is missing or unclearRead from sources, not yet reviewed

What to learn next

Ordered by what would most change how you read this page, starting with what is easiest to misunderstand.

This order is fixed in code and does not count clicks or time on the page.

What is not here

3 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 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.

The most potent CYP2D6 inhibitor among the serotonin reuptake inhibitors, effective in adults by the largest network meta-analysis but carrying a label that states effectiveness was not demonstrated in three placebo-controlled trials in 752 treated adolescents — the population its own 2001 publication described as responding well, and whose restored data set in 2015 showed a Hamilton fall of 10.7 points against 9.1 on placebo (p=0.20) with increased suicidal ideation and behaviour.

Recorded evidence blocks (12)

What did Paroxetine's largest trial (3255526 people) and its longest (14 years) measure?


3255526 people in Paroxetine's largest registered study, 14 years in its longest registered window, measuring Change From Baseline Short Form (SF)-12/36 Physical Function Over the Course of the Year After Injury. ClinicalTrials.gov · 2026-09-01

49 phase4, 37 phase3, 29 phase1, 23 na, 21 phase2, 16 na or unstated, 2 early phase1; NCT00338962; 2015-07; no ageing endpoint recorded. Last human test completed 2026, NCT06049797.

Interpretation These counts include studies where Paroxetine was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.

Show the evidence
  • phase4
    49
  • phase3
    37
  • phase1
    29
  • na
    23
  • phase2
    21
  • na or unstated
    16
2 more recorded rows
  • early phase1
    2
  • Last recorded human test NCT06049797
    2026-05-07

recorded 2026-09-01 · last checked 2026-09-04

From C. elegans to human: where has Paroxetine shown lifespan?


C. elegans: lifespan, mouse: biomarker, rat: mechanism-only and human: healthspan (173): the rungs where Paroxetine has a recorded finding. Europe PMC and ClinicalTrials.gov · organism ladder · 2026-09-01

Change From Baseline Short Form (SF)-12/36 Physical Function Over the Course of the Year After Injury — the recorded outcome words.

Yeast C. elegans lifespanDrosophila Mouse biomarkerRat mechanism-onlyDog Non-human primate Human healthspan
Show the evidence
  • C. elegans
    lifespan
  • mouse
    biomarker
  • rat
    mechanism-only
  • human NCT02655354
    healthspan; Change From Baseline Short Form (SF)-12/36 Physical Function Over the Course of the Year After Injury; 173

recorded 2026-09-01 · last checked 2026-09-04

15 of Paroxetine's trials stopped: futility/efficacy, accrual/recruitment, funding/business, other?


futility/efficacy (1), accrual/recruitment (6), funding/business (2) and other (6): Paroxetine's stop wording, clustered. ClinicalTrials.gov · 2026-09-01

"recruitment difficulties"; 15 of 173 registered studies

Show the evidence

Trial

  • NCT00202449
    terminated; "recruitment difficulties"
  • NCT00249847
    terminated; "Unable to complete accrual; elected to close the study in April 2008."
  • NCT00400088
    terminated; "Recruitment difficulties"
  • NCT00429169
    terminated; "Interim analysis showed differential treatment effects."
  • NCT00557622
    terminated; "difficulty in achieving target enrollment numbers"
  • NCT00641173
    withdrawn; "Withdrawn by funding source"
9 further recorded trials
  • NCT00658008
    terminated; "Please see Detailed Description for termination reason."
  • NCT00658372
    terminated; "Please see Detailed Description for termination reason."
  • NCT00658762
    terminated; "Please see Detailed Description for termination reason."
  • NCT00836069
    terminated; "Pfizer has terminated the execution of this protocol"
  • NCT00926835
    terminated; "due to patient recruitment difficulties"
  • NCT01416220
    withdrawn; "recruitment difficulties"
  • NCT01841502
    terminated; "Telaprevir will not be used in NL, no more inclusions are expected."
  • NCT02893371
    terminated; "Per PI, this study is not a clinical trial and was inadvertently entered in the system"
  • NCT04757571
    withdrawn; "Institutional and funding constrains"

recorded 2026-09-01 · last checked 2026-09-04

Human studies of Paroxetine used Paroxetine Hydrochloride Controlled-Release Tablets 25 mg — over how long?


studies of Paroxetine used the recorded amount. ClinicalTrials.gov · 2026-09-01

16 recorded entries; human; tablet; also "Paroxetine Hydrochloride Controlled-Release Tablets 25 mg", "Paxil CR™ Tablets 25 mg", "Paroxetine hydrochloride 40 mg tablet"

Show the evidence

human

  • NCT00647881
    Paroxetine Hydrochloride Controlled-Release Tablets 25 mg
  • NCT00647881
    Paxil CR™ Tablets 25 mg
  • NCT00648193
    tablet; Paroxetine hydrochloride 40 mg tablet
  • NCT00648193
    Paxil® 40 mg Table
  • NCT00650403
    Paxil® 40 mg Tablet
  • NCT00812812
    tablet; paroxetine 10mg tablet
10 more recorded rows
  • human NCT00812812
    tablet; paroxetine 20mg tablet
  • human NCT00812812
    matched placebo to paroxetine 10mg
  • human NCT00812812
    matched placebo to paroxetine 20mg
  • human NCT02097147
    Paroxetine 20 mg
  • human NCT03504475
    Paroxetine Hydrochloride Tablet 20 mg
  • human NCT03504475
    Paxil® 20 mg
  • human NCT04188028
    Paroxetine 10Mg Tablet
  • human NCT04188028
    Paroxetine 20Mg Tablet
  • human NCT05992428
    Paroxetine 20mg
  • human NCT06025474
    Paroxetine 20 Mg Oral Tablet

recorded 2026-09-01 · last checked 2026-09-04

Paroxetine's half-life is 21 hours — which schedules were studied?


21 hours, the half-life Paroxetine's label states. openfda-label · 598ece4d-0ac4-993b-e063-6294a90a1d34 · 2026-08-30

Show the evidence
  • half life
    21 hours hours; Elimination Metabolism The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days of paroxetine.
  • bioavailability
    Paroxetine is equally bioavailable from the oral suspension and tablet.
  • metabolism
    The excess accumulation is a consequence of the fact that 1 of the enzymes that metabolizes paroxetine is readily saturable.

recorded 2026-08-30 · last checked 2026-09-04

Which of 18fdg pet pdss ham a, adverse events all and bioequivalence did Paroxetine's trials measure?


18fdg pet pdss ham a, adverse events all and bioequivalence lead 40 outcome terms across Paroxetine's trials. ClinicalTrials.gov · 2026-09-01

hamilton depression rating scale scores, hamilton anxiety scale total, ham d 17, depressive symptom scores, caps recurrent distressing dreams item and pain levels follow.

Show the evidence
  • hamilton depression rating scale
    1
  • hamilton depression scale
    1
  • liebowitz social anxiety scale
    1
  • hamilton depression rating scale scores
    1
  • hamilton anxiety scale total
    1
  • ham d 17
    1
14 more recorded rows
  • depressive symptom scores
    1
  • caps recurrent distressing dreams item
    1
  • pain levels
    1
  • clinician administered ptsd scale
    1
  • side effects
    1
  • semen volume
    1
  • sperm concentration
    1
  • sperm motility
    1
  • sperm morphology
    1
  • hamilton anxiety rating scale
    1
  • changes in neuropsychiatric inventory
    1
  • changes in cornell s depression scale
    1
  • changes in updrs subscale
    1
  • hamilton depression rating scale total
    1

recorded 2026-09-01 · last checked 2026-09-04

Which of Paroxetine's 7 ongoing trials reports first?


7 registered trials of Paroxetine are open; earliest completion 2026-02-10. ClinicalTrials.gov · 2026-09-01

M/P ratio; Treatment Response; latest 2030-03

Show the evidence

Trial

  • NCT03511118
    "Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants"; n 1600; "M/P ratio"; 2028-07-31
  • NCT06337539
    "Precision Psychiatry for Depression: Immune Response and Affective Symptoms as Predictors of Response to Antidepressants"; n 50; "Treatment Response"; 2027-07-31
  • NCT06799169
    "Management of Acute Tinnitus With Migraine Medications"; n 100; "Tinnitus Functional Index"; 2026-12
  • NCT07057011
    "Therapeutic Outcomes of Selective Serotonin Reuptake Inhibitors and Phosphodiesterase-5 Inhibitors Combination Therapy Versus Monotherapy"; n 60; "Treatment of premature ejaculation"; 2026-02-10
  • NCT07070232
    "A Clinical Study to Test if an Investigational Treatment Called BNT326 is Safe and Potentially Beneficial When Used Alone or in Combination With Other Investigational Treatments Such as BNT327, for People With Advanced Malignant Tumors"; n 1438; "Parts 1 and 2 - All cohorts except Cohort 1F - Occurrence of treatment emergent adverse events (TEAEs), treatment related adverse events (TRAEs), treatment emergent serious adverse events (TESAEs), and treatment related serious adverse…"; 2030-03
  • NCT07669571
    "A Phase I Study of NS-079 in Healthy Participants"; n 78; "Number of Participants with Treatment-Related Adverse Events"; 2027-05
  • 1 further recorded trial NCT07715669
    "Antidepressant Therapy for Improved Blood Vessel Health After Preeclampsia"; n 40; "Microvascular endothelium-dependent dilation response measured by laser-Doppler flowmetry"; 2027-06

recorded 2026-09-01 · last checked 2026-09-04

Which 90 trials of Paroxetine posted no result?


Posted no result
90 of 90 completed trials
Registrations
NCT01049347, NCT00018733, NCT00516113, NCT00610610, NCT00610909 and NCT00457106, and 84 more
Completion dates
oldest 2000-05; newest 2024-07-03
Show the evidence

Trial

  • NCT01049347
    2000-05
  • NCT00018733
    2001-12
  • NCT00516113
    2002-11
  • NCT00610610
    2002-12
  • NCT00610909
    2002-12
  • NCT00457106
    2003-06
14 further recorded trials
  • NCT00178035
    2003-08
  • NCT00048204
    2003-09-30
  • NCT00018759
    2003-10
  • NCT00100464
    2003-12
  • NCT00178048
    2003-12
  • NCT00177567
    2004-01
  • NCT00715039
    2004-05
  • NCT00825058
    2004-10
  • NCT01371461
    2004-10
  • NCT00825019
    2004-12
  • NCT00647881
    2005-05
  • NCT00648427
    2005-05
  • NCT00031317
    2005-06
  • NCT00489775
    2005-06

At the median, Paroxetine's trials enrolled 95 people — anything larger?


Median enrolment
95
Largest enrolment
3255526
Registered trials counted
167

Paroxetine and CYP3A4 and CYP2D6: shared by which compounds?


CYP3A4 and CYP2D6 appear in Paroxetine's recorded interaction sentences, 5 in all. openfda-label+europepmc · 2026-08-30

Interpretation pharmacokinetics

Show the evidence

CYP2D6

  • pharmacokinetics
    The metabolism of paroxetine is accomplished in part by CYP2D6.
  • pharmacokinetics
    Pharmacokinetic behavior of paroxetine has not been evaluated in subjects who are deficient in CYP2D6 (poor metabolizers).

CYP3A4

  • pharmacokinetics
    In addition, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than paroxetine as an inhibitor of the metabolism of several substrates for this enzyme, including terfenadine, triazolam and cyclosporine.
  • pharmacokinetics
    Paroxetine's extent of inhibition of CYP3A4 activity is not expected to be of clinical significance.
  • pharmacokinetics
    Drugs Metabolized by Cytochrome CYP3A4 An in vivo interaction study involving the co-administration under steady-state conditions of paroxetine and terfenadine, a substrate for CYP3A4, revealed no effect of paroxetine on terfenadine pharmacokinetics.

recorded 2026-08-30 · last checked 2026-09-04

Was Paroxetine studied with fasting and exercise?


fasting and exercise are named in Paroxetine's label sentences: "Fasting gall-bladder volumes of 21.8 +/- 3.2 ml on placebo and 28.0 +/- 3.5 ml on paroxetine were similar." openfda-label+europepmc · 2026-08-30

2 recorded statements; fasting, exercise

Show the evidence
  • fasting
    Fasting gall-bladder volumes of 21.8 +/- 3.2 ml on placebo and 28.0 +/- 3.5 ml on paroxetine were similar.
  • exercise
    A total of 75 outpatients with panic disorder with or without agoraphobia (DSM-IV and ICD-10) received either (1) exercise plus paroxetine 40 mg/day (n=21), (2) relaxation plus paroxetine (n=17), (3) exercise plus pill placebo (n=20), or (4) relaxation plus pill placebo (n=17).

recorded 2026-08-30 · last checked 2026-09-04

What is recorded about Paroxetine and sirtuin?


"SIRT1 may regulate paroxetine metabolism through CYP2D6 acetylation, supporting the role of the "SIRT1-CYP2D6 acetylation axis" in precision treatment." — where Paroxetine and sirtuin appear together. Europe PMC · pathway abstract search · 2026-07-21

sirtuin, mTOR, autophagy, AMPK; PMID 42479501, 38879805, 32039209, 30290216

Show the evidence
  • sirtuin PMID 42479501
    "SIRT1 may regulate paroxetine metabolism through CYP2D6 acetylation, supporting the role of the "SIRT1-CYP2D6 acetylation axis" in precision treatment."

mTOR

  • PMID 38879805
    "Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells."
  • PMID 38879805
    "Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA."
  • "We propose a fully oral, low-cost, four-component regimen designed to replicate ketamine's entire plasticity cascade: (1) dextromethorphan (DXM) supplies fast NMDA antagonism; (2) a strong CYP2D6 inhibitor (fluoxetine, paroxetine, or high-dose duloxetine) prolongs DXM exposure without relying on bupropion; (3) the AMPA positive allosteric modulator piracetam amplifies the downstream glutamate…"

autophagy

  • PMID 32039209
    "Here, we identified paroxetine hydrochloride (Paxil) as a late autophagy inhibitor and investigated its killing effect on lung cancer cells and with a xenograft mouse model <i>in vivo</i>."
  • PMID 32039209
    "Upregulated LC3-II and p62 expression indicated that Paxil inhibited autophagy."
  • PMID 32039209
    "Thus, Paxil blocked the autophagic flux and induced the mitochondria-dependent apoptosis via the ROS-MAPK pathway."

AMPK

  • PMID 30290216
    "A number of hormones and pharmacological agents have been reported to activate AMPK including paroxetine, metformin, thiazolidinediones, adiponectin, leptin, interleukin-6, and etc."
  • PMID 25839176
    "Given that AMP-activated protein kinase (AMPK) is a master switch for energy homeostasis, we aimed to determine whether selective serotonin reuptake inhibitor paroxetine enhances energy metabolism by activating AMPK in neuroblastoma cells."
  • PMID 25839176
    "We found that paroxetine dose dependently increased mitochondrial biogenesis, which involves the AMPK-peroxisome proliferator-activated receptor-γ coactivator-1α pathway."

recorded 2026-07-21 · last checked 2026-09-04

Where it is registered
Identifiers, relations and other names

The exact record

PubChem CID
667572
CAS number
112058-85-2
InChIKey
AHOUBRCZNHFOSL-RHSMWYFYSA-N
Salt form
Paroxetine Hydrochloride, Paroxetine Hydrochloride Hemihydrate, Paroxetine Hydrochloride Anhydrous, Paroxetine Mesylate
Trade name
Paxil, Pexeva, Brisdelle, PAXIL CR, Paxil / Paxil CR / Pexeva / Brisdelle
Also called
(+)-TRANS-PAROXETINE, PAROXETINE HYDROCHLORIDE RELATED COMPOUND C [USP IMPURITY], PAROXETINE, TRANS-(+)-
Sources (10)

Sources

  • ClinicalTrials.gov clinicaltrials.gov ·
  • ClinicalTrials.gov ClinicalTrials.gov API v2 snapshot 2026-09-01T09:00:05 ·
  • this record's own fields 2,3,5 ·
  • Europe PMC dose-response search ·
  • Europe PMC pathway abstract search ·
  • Europe PMC search ·
4 more sources

ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work

How these records are assembled · Which registers were checked

Index-quality checks
  • identity passed: no open identity hold
  • 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: 10 source rows
  • no critical contamination: no quarantine open
  • canonical metadata passed: slug and display name present
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