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Bupropion

  • 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 Bupropion does in the body

Depression, and help with quitting smoking

Most antidepressants act on serotonin. Bupropion does not. It slows the removal of two other messengers, dopamine and norepinephrine, from the gaps between nerve cells. Separately, it plugs the receptor that nicotine binds to, which is why the same molecule sold under a different name helps people stop smoking: the cigarette stops delivering as much of a reward.

What happened in people

A 64% relative increase in six-month smoking abstinence over placebo, high-certainty, across 45 trials and 17,866 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.

The limit that matters most

That naltrexone-bupropion is cardiovascularly safe — LIGHT was terminated before it could assess its own non-inferiority margin

Where it acts
Dopaminergic and noradrenergic terminals in prefrontal cortex and striatum; nicotinic receptors in ventral tegmental area
Kind of result
The kind of result is not recorded
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 C13H18ClNO•HCl, weighing 276.2.

    US prescribing information · d5469d64-5e74-4b7a-b4cd-551665f6adaa · read 2026-08-30

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 84 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.

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 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.

Incidence of moderate-to-severe neuropsychiatric adverse events in psychiatric and non-psychiatric cohorts

The study showed what it set out to show

Who was studied
EAGLES (NCT01456936)
How many people
8144
Study design
Phase 4
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Bupropion-placebo risk difference -0.08 (95% CI -1.37 to 1.21) non-psychiatric; 1.78 (-0.24 to 3.81) psychiatric
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. Insomnia was the most frequent adverse event in the bupropion group, 12% of 2,006 participants.

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

Form and route. Oral tablet: immediate release, sustained release (SR) and extended release (XL)

Interval reported. 95% CI -1

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

Time to first major adverse cardiovascular event, non-inferiority margin 1.4

The study did not show it

Who was studied
LIGHT (NCT01601704)
How many people
8910
Study design
Phase 3 cardiovascular outcome trial, terminated early
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
HR 0.88 at 50% of planned events (adjusted 99.7% CI 0.57 to 1.34); non-inferiority to a margin of 1.4 could not be assessed
Repeated elsewhere
Unreplicated

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. Gastrointestinal adverse events 14.2% vs 1.9% and central nervous system symptoms 5.1% vs 1.2%, both P < .001.

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

Form and route. Oral tablet: immediate release, sustained release (SR) and extended release (XL)

Interval reported. Not recorded in this summary

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

Smoking abstinence at six months or longer

The study showed what it set out to show

Who was studied
Cochrane antidepressants for smoking cessation (bupropion arm)
How many people
17866
Study design
Systematic review and meta-analysis
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
RR 1.64 (95% CI 1.52 to 1.77), high-certainty evidence
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. No limitation is recorded for this study.

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

Form and route. Oral tablet: immediate release, sustained release (SR) and extended release (XL)

Interval reported. 95% CI 1

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 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

    Bupropion

    What a person takes: Oral tablet: immediate release, sustained release (SR) and extended release (XL).

    The measurement behind this step

    Three release profiles with different dosing schedules. The release profile is clinically relevant rather than cosmetic, because seizure risk tracks peak plasma concentration, and it is why a 300 mg generic that failed bioequivalence was withdrawn rather than relabelled.

  2. Getting in

    Swallowed, then largely converted to something else

    Most of what reaches the bloodstream long-term is not bupropion itself but a chemical the liver makes from it.

    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

    Extensive hepatic metabolism, principally by CYP2B6, to hydroxybupropion, which circulates at far higher concentrations than the parent and has a longer half-life. Threohydrobupropion and erythrohydrobupropion are also formed. The pharmacology patients experience is largely metabolite pharmacology.

  3. Reaching the cell

    Crosses into the brain

    Both the drug and its main breakdown product reach brain tissue.

    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

    Bupropion and hydroxybupropion cross the blood-brain barrier and reach dopaminergic and noradrenergic terminal fields in prefrontal cortex, striatum and the ventral tegmental projection system.

  4. What it acts on

    Blocks two reuptake pumps, and one receptor

    It slows the clearance of dopamine and norepinephrine from the gaps between nerve cells, and separately plugs the receptor nicotine uses.

    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

    Inhibits the dopamine transporter (SLC6A3) and norepinephrine transporter (SLC6A2), and acts as a non-competitive antagonist at nicotinic acetylcholine receptors including the alpha-4 beta-2 subtype. The nicotinic action is the mechanistic basis for the smoking cessation indication and is largely attributed to hydroxybupropion.

  5. The change it makes

    Catecholamine tone rises; nicotine reward falls

    Two effects at once: more of the alerting messengers stay around, and a cigarette delivers less of a kick.

    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

    Raised synaptic dopamine and norepinephrine underlie the antidepressant and pro-attentional effects; nicotinic blockade blunts nicotine-evoked dopamine release in the nucleus accumbens, which reduces the reinforcing value of smoking and the intensity of withdrawal.

  6. What that does for a person

    Mood scores fall, or abstinence holds — and the seizure threshold falls with them

    The measurable results are depression scale scores and verified quit rates. The measurable cost is a dose-dependent risk of seizure.

    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

    Efficacy endpoints are rating-scale change and biochemically verified continuous abstinence. Seizure risk is dose- and peak-concentration-dependent, which is why the immediate-release ceiling is 450 mg per day in divided doses and why extended-release formulations exist at all.

No suggested links are held for this record, so nothing is hidden from this path.

What we know
The record describes 5 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 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 with major depression, particularly where sexual side effects or sedation have been a problem; adults with seasonal affective disorder; and people trying to stop smoking.

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: “Safety and effectiveness in the pediatric population have not been established.”

    US prescribing information · d5469d64-5e74-4b7a-b4cd-551665f6adaa · read 2026-08-30

  • On older people, the label states: “Of the approximately 6,000 patients who participated in clinical trials with bupropion hydrochloride sustained-release tablets (depression and smoking cessation studies), 275 were ≥65 years old and 47 were ≥75 years old.”

    US prescribing information · d5469d64-5e74-4b7a-b4cd-551665f6adaa · read 2026-08-30

  • On people who are pregnant, the label states: “Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy.”

    US prescribing information · d5469d64-5e74-4b7a-b4cd-551665f6adaa · read 2026-08-30

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

    US prescribing information · d5469d64-5e74-4b7a-b4cd-551665f6adaa · read 2026-08-30

  • On people with reduced liver function, the label states: “In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum bupropion hydrochloride extended-release tablets (XL) dose is 150 mg every other day.”

    US prescribing information · d5469d64-5e74-4b7a-b4cd-551665f6adaa · read 2026-08-30

  • On people with reduced kidney function, the label states: “Consider a reduced dose and/or dosing frequency of bupropion hydrochloride extended-release tablets (XL) in patients with renal impairment (glomerular filtration rate: <90 mL/min).”

    US prescribing information · d5469d64-5e74-4b7a-b4cd-551665f6adaa · read 2026-08-30

Where the result stopped carrying

  • LIGHT terminated after interim results were disclosed, leaving the cardiovascular safety question open
  • Budeprion XL 300 mg withdrawn in 2012 for non-bioequivalence
  • The original immediate-release product carried a seizure incidence high enough to require a hard daily dose ceiling and the development of slower-release forms
  • 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 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 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: immediate release, sustained release (SR) and extended release (XL)

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: S6.

No source is stored against this line.

What is in the pack

Three release profiles with different dosing schedules.

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. The rest of the recorded wording: The release profile is clinically relevant rather than cosmetic, because seizure risk tracks peak plasma concentration, and it is why a 300 mg generic that failed bioequivalence was withdrawn rather than relabelled.

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.

The recorded stepping schedule

  • What follows is the schedule printed on the label, recorded as it is written there. It is a record of what was done, not a recommendation.

    US prescribing information · 004d8121-59d4-46c4-acb8-b2dd097bf556 · read 2026-08-27

  • Starting dose (major depressive disorder): 150 mg once daily in the morning

    US prescribing information · 004d8121-59d4-46c4-acb8-b2dd097bf556 · read 2026-08-27

  • After 4 days of dosing: 300 mg once daily in the morning — Target dose as stated in the label schedule

    US prescribing information · 004d8121-59d4-46c4-acb8-b2dd097bf556 · read 2026-08-27

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

The US label carries a boxed warning for suicidal thoughts and behaviours in children, adolescents and young adults. Bupropion is contraindicated in seizure disorders, in patients with current or prior bulimia or anorexia nervosa, and during abrupt discontinuation of alcohol or benzodiazepines, because all raise seizure risk. Common adverse effects are insomnia, dry mouth, headache, agitation and nausea. It should not be combined with MAO inhibitors.

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: immediate release, sustained release (SR) and extended release (XL)

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

A recorded note compares this form with the others that are sold. It is kept below, word for word.

A fixed RNAWiki sentence

Where this came from

Wording RNAWiki always uses, not a finding about this substance.

The recorded note, unchanged: The release profile is clinically relevant rather than cosmetic, because seizure risk tracks peak plasma concentration, and it is why a 300 mg generic that failed bioequivalence was withdrawn rather than relabelled.

No source is stored against this line.

What is recorded as being sold

  • 399 products list this as an active ingredient in the United States drug directory. 394 of them contain it and nothing else.

    FDA National Drug Code directory · 71610-708 · read 2026-08-29

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

    FDA National Drug Code directory · 71610-708 · read 2026-08-29

  • The regulator's established pharmacologic class for it is aminoketone [epc], dopamine uptake inhibitors [moa] and increased dopamine activity [pe].

    FDA National Drug Code directory · 71610-708 · read 2026-08-29

  • 258 published labels name it as an active ingredient. 256 of them describe this substance alone, which is where its own label text on this page comes from.

    US prescribing information · d5469d64-5e74-4b7a-b4cd-551665f6adaa · read 2026-08-29

  • Those labels are classed as human prescription drug.

    US prescribing information · d5469d64-5e74-4b7a-b4cd-551665f6adaa · read 2026-08-29

  • buPropion Hydrochloride XL is extended-release tablets at 150 mg, 300 mg, recorded as prescription product; fda label in effect 2025-11-25 in the United States.

    US prescribing information · 004d8121-59d4-46c4-acb8-b2dd097bf556 · read 2026-08-27

  • Recorded price in US: 0.09421–0.11511 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 26 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 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 Bupropion 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 naltrexone-bupropion is cardiovascularly safe — LIGHT was terminated before it could assess its own non-inferiority margin

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 bupropion is better tolerated than an SSRI overall, when it avoids one serotonergic side effect and adds insomnia, agitation and a dose-dependent seizure risk

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 150 mg strength bioequivalence of a generic guarantees the 300 mg strength, which is precisely the extrapolation the 2012 withdrawal falsified

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 Bupropion 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.

High-certainty Cochrane evidence: 64% relative increase in long-term quit rates
In plain words
Across 45 trials and nearly 18,000 people, bupropion raised the chance of still being off cigarettes six months or more later by about two thirds compared with placebo.
What was measured
Smoking abstinence at six months or longer, relative risk versus placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Howes et al. included 115 studies. Bupropion increased long-term smoking cessation with high-certainty evidence: RR 1.64 (95% CI 1.52 to 1.77), I-squared 15%, 45 studies, 17,866 participants. Bupropion was inferior to varenicline (RR 0.71, 95% CI 0.64 to 0.79; 6 studies, 6,286 participants) and no different from nicotine replacement (RR 0.99, 95% CI 0.91 to 1.09; 10 studies, 8,230 participants). Dropouts due to adverse events were higher on bupropion than placebo (RR 1.37, 95% CI 1.21 to 1.56, high certainty).
Source
Howes S et al., Cochrane Database Syst Rev 2020;4:CD000031
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
EAGLES removed the neuropsychiatric boxed warning that the FDA had imposed in 2009
In plain words
A trial of 8,144 smokers, half of them with a psychiatric diagnosis, found no excess of serious mood or behaviour problems on bupropion compared with placebo or a nicotine patch. The warning came off.
What was measured
Incidence of moderate-to-severe neuropsychiatric adverse events; continuous abstinence weeks 9-12
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
EAGLES (NCT01456936) randomised 8,144 smokers into psychiatric and non-psychiatric cohorts. In the non-psychiatric cohort, moderate-to-severe neuropsychiatric adverse events occurred in 22 of 989 on bupropion (2.2%) versus 24 of 999 on placebo (2.4%); bupropion-placebo risk difference -0.08 (95% CI -1.37 to 1.21). In the psychiatric cohort, 68 of 1,017 (6.7%) versus 50 of 1,015 (4.9%); risk difference 1.78 (-0.24 to 3.81). Bupropion beat placebo on abstinence (OR 2.07, 95% CI 1.75 to 2.45) and lost to varenicline (OR 1.75 favouring varenicline, 1.52 to 2.01). The trial was funded by Pfizer and GlaxoSmithKline, the manufacturers of the two drugs under investigation.
Source
Anthenelli RM et al., Lancet 2016;387:2507-2520
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
LIGHT: the cardiovascular outcome trial was terminated after its interim data leaked
In plain words
A trial testing whether the naltrexone-bupropion weight-loss combination was safe for the heart was stopped early after partial results were made public, and it can no longer answer the question it was designed to answer.
What was measured
Time to first major adverse cardiovascular event
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
LIGHT (NCT01601704) randomised 8,910 overweight or obese patients at increased cardiovascular risk. At the 25% interim, MACE occurred in 59 placebo patients (1.3%) and 35 on naltrexone-bupropion (0.8%); HR 0.59, 95% CI 0.39 to 0.90. At 50% of planned events the estimate had moved to 102 (2.3%) versus 90 (2.0%); HR 0.88, adjusted 99.7% CI 0.57 to 1.34. Because of unanticipated early termination the pre-specified non-inferiority margin of 1.4 could not be assessed. Nissen et al. concluded that cardiovascular safety remains uncertain and requires a new adequately powered trial. Adverse effects were more common on the combination: gastrointestinal 14.2% versus 1.9% (p<0.001), central nervous system 5.1% versus 1.2% (p<0.001).
Source
Nissen SE et al., JAMA 2016;315:990-1004
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
A 300 mg generic was withdrawn in 2012 after failing bioequivalence
In plain words
One generic version of the 300 mg extended-release tablet did not release the drug the same way as the original. The FDA pulled it and changed how it approves generics of this class.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Woodcock, Khan and Yu, writing from the FDA Center for Drug Evaluation and Research, described the withdrawal of budeprion XL 300 mg for non-bioequivalence to the reference bupropion hydrochloride extended-release product. The original approval had relied on bioequivalence data from the 150 mg strength with the 300 mg strength waived by extrapolation; direct study of the 300 mg strength did not meet the standard. This is the reason the bupropion formulation on a prescription is a clinically relevant fact rather than a pharmacy detail.
Source
Woodcock J, Khan M, Yu LX. N Engl J Med 2012;367:2463-2465
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
The "no sexual side effects" advantage is real and mostly measured indirectly
In plain words
Bupropion does not act on serotonin, and serotonin is the pathway behind SSRI sexual dysfunction. The absence of the side effect follows from the mechanism more than from a large dedicated trial programme.
What was measured
That bupropion is generally better tolerated than an SSRI, when what is well established is that it avoids one specific serotonergic side effect while adding insomnia, agitation and seizure risk
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The pharmacological premise is solid: bupropion has no meaningful affinity for the serotonin transporter, and SSRI-associated sexual dysfunction is a serotonergic class effect. The clinical evidence base is smaller and less systematic than the efficacy base — it rests on secondary endpoints and comparative trials rather than on a programme designed around sexual function as a primary outcome. The Cochrane smoking review found bupropion produced more psychiatric adverse events than placebo (RR 1.25, 95% CI 1.15 to 1.37; 6 studies, 4,439 participants), so "better tolerated" is not true across the board.
Source
Howes S et al., Cochrane Database Syst Rev 2020;4:CD000031
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
Adult ADHD: a real but modest effect in the Cortese network
In plain words
In the largest comparison of ADHD medicines, bupropion beat placebo in adults on clinician ratings, but by less than the stimulants did.
What was measured
Standardised mean difference on clinician-rated ADHD core symptoms in adults
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Cortese et al. pooled 133 double-blind randomised trials. In adults, on clinician-rated core ADHD symptoms closest to 12 weeks, bupropion gave SMD -0.46 (95% CI -0.85 to -0.07), against -0.79 (-0.99 to -0.58) for amphetamines and -0.49 (-0.64 to -0.35) for methylphenidate. Bupropion is not FDA-approved for ADHD; this is an off-label use with network-level evidence behind it.
Source
Cortese S et al., Lancet Psychiatry 2018;5:727-738
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

How many documents were read

  • 251 documents were read for this substance.

    RNAWiki source record

  • 120 of them state the same halfLife, and they agree.

    RNAWiki source record

  • 131 of them state the same bioavailability, and they agree.

    RNAWiki source record

Where else this substance is registered

FDA substance identifier (UNII)
ZG7E5POY8O
CAS registry number
34911-55-2
PubChem compound
444
RxNorm concept
203204

Checks this page had to pass

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  • Not passed

    Trial roles classified for highlighted evidence

    No registered study is classified as testing this substance.

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  • Passed

    Safety mode resolved

    Suppression classes recorded: 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

  • 74 approved applications cover products containing this substance. The earliest was NDA018644, approved 19851230 to GLAXOSMITHKLINE.

    Drugs@FDA application register · NDA018644 · read 2026-08-29

  • Marketing status on the register: discontinued, none (tentative approval) and prescription.

    Drugs@FDA application register · NDA018644 · read 2026-08-29

  • The earliest marketing start date recorded for a listed product is 19961004.

    FDA National Drug Code directory · 71610-708 · 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.

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What is not here

7 questions this page could not answer

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  • What was measured, goal by goal — found nothing in the sources checked.
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  • 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.
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The record as stored

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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 antidepressant that skips serotonin entirely, with high-certainty Cochrane evidence that it raises long-term smoking quit rates by 64% — and a seizure risk that forced a dose ceiling, a generic that failed bioequivalence, and a cardiovascular outcome trial terminated for leaked interim data.

Recorded evidence blocks (11)

On the Bupropion label: indicated for what?


"Bupropion hydrochloride extended-release tablet (XL) is an aminoketone antidepressant, indicated for: treatment of major depressive disorder (MDD) ( 1.1 ) prevention of seasonal affective disorder (SAD) ( 1.2 ) 1.1 Major Depressive Disorder (MDD) Bupropion hydrochloride extended-release tablets (XL) are indicated for…": indications and usage on Bupropion's label. DailyMed label · bcbef1b4-a135-4231-bc65-7d0b335260e8 · 2026-08-26

259 registered trials of Bupropion — at which phases?


Registered studies posting no result
158 of 259

259 registered studies of Bupropion: 72 phase4, 60 phase2, 55 phase1, 49 phase3, 32 na, 7 na or unstated, 5 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01

808 with a PubMed record

Show the evidence
  • phase4
    72
  • phase2
    60
  • phase1
    55
  • phase3
    49
  • na
    32
  • na or unstated
    7
8 more recorded rows
  • early phase1
    5
  • completed
    190
  • unknown
    23
  • terminated
    20
  • recruiting
    10
  • withdrawn
    7
  • not yet recruiting
    5
  • active not recruiting
    4

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

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


futility/efficacy (1), accrual/recruitment (15), funding/business (2) and other (7): Bupropion's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01

"This study was closed early due to poor accrual"; 25 of 259 registered studies

Show the evidence

Trial

  • NCT00032084
    terminated; "This study was closed early due to poor accrual"
  • NCT00119210
    terminated; "We were unable to recruit sufficient numbers of patients and decided that the study protocol was not feasible to implement"
  • NCT00181896
    terminated; "Study was terminated due to lack of recruitment"
  • NCT00248118
    terminated; "PI left NIH"
  • NCT00429169
    terminated; "Interim analysis showed differential treatment effects."
  • NCT00449007
    terminated; "recruitment of this population was not feasible"
14 further recorded trials
  • NCT00511134
    terminated; "Study has been terminated due low recruitment of participant population."
  • NCT00958633
    terminated; "Recruitment was stopped before the planned sample size was reached owing to the Covid-19 pandemic and expiration of funding."
  • NCT01046214
    terminated; "Recruitment issues"
  • NCT01048983
    withdrawn; "No accrual."
  • NCT01219673
    terminated; "Low accrual."
  • NCT01560507
    terminated; "Low Recruitment"
  • NCT01942187
    withdrawn; "No participants enrolled."
  • NCT02238977
    terminated; "Study stopped due to difficulty recruiting"
  • NCT02582008
    terminated; "Slow accrual"
  • NCT02893371
    terminated; "Per PI, this study is not a clinical trial and was inadvertently entered in the system"
  • NCT03132571
    terminated; "Study discontinued due to funding."
  • NCT03278938
    withdrawn; "PI Retired and no data was collected"
  • NCT03326128
    terminated; "Due to the COVID-19 pandemic, it was difficult to recruit eligible participants."
  • NCT03852160
    withdrawn; "New design was developed to better fit company strategy, a new study has replaced 5413541TRD3011 study"

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

Human studies of Bupropion used Abrika Bupropion 150 mg XL Tablet, single dose — over how long?


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

16 recorded entries; human; tablet; also "Abrika Bupropion 150 mg XL Tablet, single dose", "Wellbutrin XL® 150 mg Tablet, single dose", "Bupropion 150 mg Extended-Released Tablet, single dose"

Show the evidence

human

  • NCT00863941
    Abrika Bupropion 150 mg XL Tablet, single dose
  • NCT00863941
    Wellbutrin XL® 150 mg Tablet, single dose
  • NCT00865111
    Bupropion 150 mg Extended-Released Tablet, single dose
  • NCT00865111
    Wellbutrin SR® 150 mg Sustained-Release Tablet, single dose
  • NCT00865371
    Abrika Bupropion 150 mg Extended-Released Tablet
  • NCT00865371
    Wellbutrin SR® 150 mg Extended-Release Tablet, single dose
10 more recorded rows
  • human NCT00883155
    Bupropion HCl 100 mg Tablets (Invamed Inc.)
  • human NCT00883155
    Wellbutrin 100 mg Tablets (Glaxo Wellcome)
  • human NCT01731067
    bupropion 25 mg
  • human NCT02438072
    Bupropion (20 mg, N06AX12)
  • human NCT02698553
    tablet; Bupropion HCl XL tablet 150mg
  • human NCT02698553
    tablet; Bupropion HCl XL tablet 300mg
  • human NCT03058419
    Bupropion 150 mg
  • human NCT03180294
    Bupropion 150 mg XL
  • human NCT04553263
    Naltrexone HCl/Bupropion HCl 8 Mg-90 Mg
  • human NCT06609343
    Bupropion Hydrochloride 150 MG

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

Bupropion's half-life is 32±14 hours — which schedules were studied?


32±14 hours, the half-life Bupropion's label states: "The first trial demonstrated that the half-life of hydroxybupropion was significantly longer in 8 subjects with alcoholic liver disease than in 8 healthy volunteers (32±14 hours versus 21±5 hours, respectively)." DailyMed label · bcbef1b4-a135-4231-bc65-7d0b335260e8 · 2026-08-26

tmax 5 hours.

Show the evidence
  • half life pharmacokinetics
    32±14 hours; The first trial demonstrated that the half-life of hydroxybupropion was significantly longer in 8 subjects with alcoholic liver disease than in 8 healthy volunteers (32±14 hours versus 21±5 hours, respectively).
  • tmax pharmacokinetics
    5 hours; Absorption Following single oral administration of bupropion hydrochloride extended-release tablets (XL) to healthy volunteers, the median time to peak plasma concentrations for bupropion was approximately 5 hours.
  • metabolism pharmacokinetics
    Metabolism Bupropion is extensively metabolized in humans.

recorded 2026-08-26 · last checked 2026-09-04

Which running trial of Bupropion could settle lifespan?


NCT05646862 measures Blinded Independent Central Review (BICR)-Assessed Progression Free Survival (PFS), reading out 2029-03-30.

1 open trial; n 420; "A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or…"

Show the evidence
  • Trial NCT05646862
    "A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy"; n 420; "Blinded Independent Central Review (BICR)-Assessed Progression Free Survival (PFS)"; 2029-03-30

Which 89 trials of Bupropion posted no result?


Posted no result
89 of 89 completed trials
Registrations
NCT00883155, NCT00000268, NCT00018187, NCT00322205, NCT00344695 and NCT00181818, and 83 more
Completion dates
oldest 1998-10; newest 2024-07-31
Show the evidence

Trial

  • NCT00883155
    1998-10
  • NCT00000268
    1998-11
  • NCT00018187
    2001-06
  • NCT00322205
    2002-03
  • NCT00344695
    2003-04
  • NCT00181818
    2003-12
14 further recorded trials
  • NCT00628225
    2003-12
  • NCT00177567
    2004-01
  • NCT01875172
    2004-01
  • NCT00307203
    2004-02
  • NCT00863941
    2004-07
  • NCT00865462
    2004-07
  • NCT00079469
    2004-08
  • NCT00249509
    2004-09
  • NCT00865371
    2004-09
  • NCT00865410
    2004-09
  • NCT00061087
    2004-10
  • NCT00044434
    2005-04
  • NCT00414180
    2005-05
  • NCT00069251
    2005-06

At the median, Bupropion's trials enrolled 74 people — anything larger?


Median enrolment
74
Largest enrolment
1037352
Registered trials counted
256

What do 20 spontaneous reports say about Bupropion — 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.

Bupropion appears in spontaneous reports to regulators. Across the 2 most-reported reaction terms, 20 reaction mentions were counted: convulsion 15; anxiety 5. FAERS via Open Targets · CHEMBL1201735 · 2026-06-24

Show the evidence
  • convulsion
    15
  • anxiety
    5

recorded 2026-06-24 · last checked 2026-09-04

Which 2 reactions does Bupropion's label not list?


anxiety and convulsion reported for Bupropion, absent from its label. FAERS via Open Targets · CHEMBL1201735 · 2026-06-24

2 label terms; 2 reported and unlisted; bcbef1b4-a135-4231-bc65-7d0b335260e8

Show the evidence
  • anxiety
    count not stated
  • convulsion
    count not stated

recorded 2026-06-24 · last checked 2026-09-04

Bupropion and CYP2B6 and CYP2D6: shared by which compounds?


CYP2B6 and CYP2D6 appear in Bupropion's recorded interaction sentences, 8 in all. DailyMed label · bcbef1b4-a135-4231-bc65-7d0b335260e8 · 2026-08-26

CYP2B6, CYP2B6, CYP2B6, CYP2D6; 4 shared nodes; drug_interactions

Show the evidence

Interaction statement

  • drug_interactions
    CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) based on clinical exposure, but should not exceed the maximum recommended dose.
  • drug_interactions
    ( 7.1 ) Drugs metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide).
  • drug_interactions
    ( 7.7 ) 7.1 Potential for Other Drugs to Affect Bupropion Hydrochloride Extended-release Tablets (XL) Bupropion is primarily metabolized to hydroxybupropion by CYP2B6.
  • drug_interactions
    Therefore, the potential exists for drug interactions between bupropion hydrochloride extended-release tablets (XL) and drugs that are inhibitors or inducers of CYP2B6.
  • drug_interactions
    Inhibitors of CYP2B6 Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure.
  • drug_interactions
    Based on clinical response, dosage adjustment of bupropion hydrochloride extended-release tablets (XL) may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see CLINICAL PHARMACOLOGY ( 12.3 )].
2 more recorded rows
  • Interaction statement drug_interactions
    Inducers of CYP2B6 Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure.
  • Interaction statement drug_interactions
    7.2 Potential for Bupropion Hydrochloride Extended-release Tablets XL to Affect Other Drugs Drugs Metabolized by CYP2D6 Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors.

CYP2B6

  • FINGOLIMOD LAURYL SULFATE, TAFAMIDIS MEGLUMINE, Arimoclomol, Sofpironium, Golodirsen, Tinidazole, Naldemedine, Methylnaltrexone
  • FINGOLIMOD LAURYL SULFATE, TAFAMIDIS MEGLUMINE, Arimoclomol, Sofpironium, Golodirsen, Tinidazole, Naldemedine, Methylnaltrexone
  • FINGOLIMOD LAURYL SULFATE, TAFAMIDIS MEGLUMINE, Arimoclomol, Sofpironium, Golodirsen, Tinidazole, Naldemedine, Methylnaltrexone
  • CYP2D6
    FINGOLIMOD LAURYL SULFATE, Darunavir Propylene Glycolate, FOSAPREPITANT DIMEGLUMINE, TAFAMIDIS MEGLUMINE, Arimoclomol, Rasagiline, Sofpironium, Fluoxetine

recorded 2026-08-26 · last checked 2026-09-04

Where it is registered
Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL1201735
PubChem CID
73416166
CAS number
849797-12-2
RxCUI
203204
InChIKey
SNPPWIUOZRMYNY-UHFFFAOYSA-N
Also called
BUPROPION HYDROBROMIDE, BUPROPION HYDROCHLORIDE, Mysimba, 323u66 sr, bupropion sr, bupropion sustained-release, bupropion xl, naltrexone, Amfebutamone, Bupropione, Bupropion extended release, Bupropion slow release
Trade name
Aplenzin, Forfivo xl, Wellbutrin, Wellbutrin 100, Wellbutrin 75, Wellbutrin sr, Wellbutrin xl, Zyban, Wellbutrin / Zyban, Budeprion
Salt form
Bupropion hbr, Amfebutamone hydrochloride, Bupropion hcl, Bupropion hydrochloride component of auvelity, Bupropion hydrochloride component of contrave, abrika bupropion 150 mg xl tablet, wellbutrin xl 150 mg tablet, Bupropion Hydrochloride Xl, Bupropion HCL ER(SR), Bupropion Hydrochloride SR
Development code
BVF-033, BW 323, BW323, NSC-315851, NSC-758686
Sources (6)

Sources

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

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: 6 source rows
  • no critical contamination: no quarantine open
  • canonical metadata passed: slug and display name present
  • no raw internal fields: enforced by the copy-contract test over the rendered page

This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.