Medication approval journey

bupropion (Wellbutrin SR)

Approved for Major depressive disorder

page first published · last updated

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FDA approvedAtypical antidepressantTaper risk: moderate

How this page reads

The page as written, with the clinical terms

Plain language uses the same facts, the same numbers and the same caveats. It does not leave anything out. Quotes from the FDA label are never reworded in either setting.

Before you stop or change your bupropion dose

Stopping abruptly causes withdrawal effects that can be severe

Withdrawal effects vary a lot across this group but are real. Any change should be prescriber-supervised rather than abrupt.

what the bupropion warnings mean

label facts below are read from the bupropion hydrochloride extended-release (sr) tablets FDA label on DailyMed, set id 0aa86bd6-b37b-45f7-a837-b067e41184e9, version 4, effective august 27, 2026. the section numbers in brackets are the label’s own. every source is linked at the end of this section. last checked 2026-10-05.

bupropion’s sustained-release form was approved for depression in 1996, and about 8 million americans filled a prescription for some form of bupropion in 2024 [meps]. it is not an ssri: it works on dopamine and norepinephrine rather than serotonin, which is why its warnings differ from the rest of the antidepressants on this site and why sexual side effects are not among them. the label carries one boxed warning and seven further warnings. this section says what each means in plain words, what the approval trials measured and for how long, which side effects the label counts and how often, and what independent research has found since, in both directions. every number is from the label or from a study in the library, and each source is linked at the end.

this is information to take to a prescriber. nothing here is a reason to start, stop or change a dose on your own.

the boxed warning: suicidal thoughts and behaviors, by age

the boxed warning says antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents and young adults in short-term trials, that the trials did not show an increase above age 24 and showed a reduction at 65 and older, and that everyone starting an antidepressant should be watched closely [label, boxed warning and 5.1].

the numbers come from 24 short-term pediatric trials of 9 antidepressants in more than 4,400 young people and 295 short-term adult trials (median two months) of 11 antidepressants in more than 77,000 adults. per 1,000 people treated, the difference against placebo was: under 18, 14 additional cases; 18 to 24, 5 additional; 25 to 64, 1 fewer; 65 and older, 6 fewer [label 5.1, table 1]. no suicides occurred in the pediatric trials. whether the risk extends beyond several months is unknown.

the bupropion label also lists the symptoms it wants families to watch for in the first months and after any dose change: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, restlessness, hypomania and mania [label 5.1]. it says a causal link to suicidality is not established, and asks that prescriptions be written for the smallest quantity consistent with good care, to reduce overdose risk.

the seven other warnings, in plain words

the label’s warnings and precautions run from 5.2 to 5.8. none is boxed. two of them, seizures and quit-smoking reactions, are the ones that shaped how this drug is dosed and prescribed.

  • mood and behaviour changes when quitting smoking [5.2]: this sr tablet is not approved for smoking cessation, but it is the same drug as zyban, and the label repeats zyban’s warning: post-marketing reports of depression, mania, psychosis, hallucinations, paranoia, aggression, agitation, anxiety, panic, suicidal thoughts, attempts and completed suicide in people taking bupropion to quit. the label notes that nicotine withdrawal itself can cause low mood, that some events occurred in people who kept smoking, and that symptoms usually resolved on stopping but persisted in some. the research section has the trial that measured this.
  • seizures [5.3]: bupropion can cause a seizure and the risk rises with dose: about 0.1% (1 in 1,000) at up to 300 mg a day, about 0.4% (4 in 1,000) at the maximum 400 mg a day. the label says not to exceed 400 mg, to increase the dose gradually, and not to restart after a seizure. it is contraindicated in anyone with a seizure disorder, a current or past diagnosis of anorexia nervosa or bulimia, or who is abruptly stopping alcohol, benzodiazepines, barbiturates or antiepileptic drugs. other drugs that lower the seizure threshold (antipsychotics, tricyclics, theophylline, systemic steroids, stimulants, cocaine), heavy alcohol use, head injury, diabetes on insulin or tablets, and low blood sugar or sodium add to the risk.
  • high blood pressure [5.4]: bupropion can raise blood pressure, and the label asks for a reading before starting and periodically after. the risk is higher with maois and other drugs that raise dopamine or norepinephrine. in a quit-smoking trial, treatment-emergent hypertension was 6.1% on bupropion plus a nicotine patch against 2.5% on bupropion alone, 1.6% on the patch alone and 3.1% on placebo, mostly in people who already had high blood pressure. the drug has not been studied in people with a recent heart attack or unstable heart disease.
  • activation of mania or hypomania [5.5]: an antidepressant can tip a depressive episode into a manic one, more so in people with bipolar disorder or risk factors for it. the label asks prescribers to screen for a personal or family history of bipolar disorder, suicide or depression first, and states that bupropion is not approved for bipolar depression.
  • psychosis and other neuropsychiatric reactions [5.6]: delusions, hallucinations, psychosis, trouble concentrating, paranoia and confusion have occurred in depressed people on bupropion, some of whom had bipolar disorder; in some cases the symptoms eased on a lower dose or on stopping.
  • angle-closure glaucoma [5.7]: the pupil dilation many antidepressants cause can trigger an attack in an eye with narrow drainage angles that has not been treated.
  • allergic reactions [5.8]: anaphylaxis-type reactions with itching, hives, swelling and breathing difficulty occurred in trials, and there are rare post-marketing reports of erythema multiforme, stevens-johnson syndrome and anaphylactic shock. rash was the single most common reason people left the trials: 2.4% at 300 mg against none on placebo [label 6.1, table 2].

what the trials measured, and for how long

the depression evidence on this label is for the older immediate-release tablet, not the sustained-release one. three placebo-controlled trials: two of 4 weeks in adult inpatients and one of 6 weeks in adult outpatients, with change on the hamilton depression rating scale as the outcome. trial 1 had 48 people on bupropion (300 to 600 mg a day) and 27 on placebo. trial 2 had 36 on 300 mg, 34 on 450 mg and 39 on placebo, and showed an effect only at 450 mg. trial 3 had 110 on 300 mg and 106 on placebo [label 14, table 6]. the placebo-subtracted differences on the depression scale were 4.7, 5.9 and 3.9 points.

the sustained-release form was approved on the basis that its blood levels match the immediate-release form, in the label’s words: "there are not as yet independent trials demonstrating the antidepressant effectiveness of the sustained-release formulation of bupropion" [label 14]. a separate placebo-controlled trial showed the sr form kept its antidepressant response for up to 44 weeks after 8 weeks of acute treatment [label 14; dossier approval record on this page].

the arithmetic that matters: the efficacy trials were 4 to 6 weeks, in a few hundred people, mostly inpatients, on a formulation most people no longer take; the longest controlled measurement was 44 weeks; and about 8 million americans a year take some form of bupropion, most of them the extended-release tablets, as outpatients, for years. the open-questions step further down this page says the same thing in fewer words.

the most common side effects, with the label’s numbers

the label compares 376 people on 300 mg a day of the sr tablet with 385 on placebo in the depression trials: headache 26% vs 23%, dry mouth 17% vs 7%, nausea 13% vs 8%, insomnia 11% vs 6%, constipation 10% vs 7%, dizziness 7% vs 5%, tremor 6% vs 1%, sweating 6% vs 2%, ringing in the ears 6% vs 2%, loss of appetite 5% vs 2% [label 6.1, table 3]. a 400 mg group of 114 people had generally higher rates. the full list is in the side-effects section lower on this page.

weight runs the opposite way from most antidepressants: 14% of people on 300 mg and 19% on 400 mg lost more than 5 pounds, against 6% on placebo, while 3% and 2% gained more than 5 pounds against 4% on placebo [label 6.1, table 4]. the label says that if weight loss is a major feature of someone’s depression, this should be weighed.

the label lists decreased libido and impotence only as infrequent reactions (fewer than 1 in 100), not in its common-reaction table [label 6.1]. the research section has the trials that measured sexual side effects directly. two cautions the label attaches to every rate: trial rates cannot be compared with other drugs’ rates, and they may not match ordinary practice.

two more label facts worth knowing: bupropion is not a controlled substance, but a single 400 mg dose produced mild amphetamine-like effects in people experienced with drugs of abuse, and seizures and deaths have been reported when tablets were crushed and inhaled or injected [label 9]. and bupropion can cause a false positive on urine screening tests for amphetamines [interactions].

what independent research says, in both directions

in favour. pooled patient-level data from 7 randomised trials (732 on bupropion, 731 on an ssri, 512 on placebo) found bupropion matched ssris on remission, 47% against 47%, both above placebo’s 36%, while causing no more sexual dysfunction than placebo [thase-2005]. when sexual function was measured with a questionnaire across antidepressants, bupropion was one of six drugs showing no significant difference from placebo, against rates of 25.8% to 80.3% for the serotonergic drugs [serretti-2009]. the cochrane review of antidepressants for quitting smoking, 50 trials and 18,577 people, found bupropion raised six-month quit rates by about 60% (risk ratio 1.60), with more dropouts for side effects (risk ratio 1.44) and no clear increase in serious adverse events [cochrane-smoking-2023]. and the cochrane review of what helps ssri-induced sexual dysfunction found that adding bupropion 150 mg twice a day beat placebo across three trials, while 150 mg once a day did not [taylor-2013].

against, or smaller than the badge suggests. in the largest comparison of antidepressants, 522 trials and 116,477 adults, bupropion beat placebo like all 21 drugs, but the certainty of evidence for most of its head-to-head comparisons was rated low to very low, so its rank is less settled than sertraline’s or escitalopram’s [cipriani-2018]. in 1,522 veterans whose depression had not responded to an antidepressant, switching to bupropion produced remission in 22.3%, adding bupropion 26.9%, and adding aripiprazole 28.9%; only the aripiprazole arm beat the bupropion switch significantly [vast-d-2017]. in the nimh-funded star*d trial, 727 people whose depression had not remitted on citalopram were switched; about one in four remitted on bupropion-sr, sertraline or venlafaxine alike, with no winner [star-d-2006].

where the warnings have been measured. the quit-smoking warning in 5.2 was tested in the eagles trial: 8,144 smokers, about half with a psychiatric diagnosis, randomised to varenicline, bupropion, a nicotine patch or placebo. neither varenicline nor bupropion produced an excess of moderate or severe neuropsychiatric events; having a psychiatric condition raised the rate, the medication did not, and the fda dropped its boxed warning on the smoking-cessation products largely on this result [eagles-2016]. the trial was designed well and paid for by the makers, with their employees among the authors, and industry-funded trials reach sponsor-friendly conclusions about 1.4 times as often as independent ones; both halves belong beside the result. on interactions, the label says bupropion blocks the liver enzyme cyp2d6 and can raise the levels of other antidepressants, antipsychotics, beta-blockers and some heart-rhythm drugs, so the dose of the other drug may need lowering [interactions].

questions to ask your prescriber about bupropion

each one comes from a warning or a study above. they are questions, not instructions; the answers depend on a history nobody here has.

  • given my age, which side of the boxed warning’s line am i on, and what exactly should i or the people around me watch for in the first two months?
  • the seizure risk is 1 in 1,000 at up to 300 mg and 4 in 1,000 at 400 mg. what dose am i on, and does anything else i take or drink lower the seizure threshold?
  • the label asks for a blood pressure reading before starting and periodically after. when was mine last checked on this dose?
  • the efficacy trials were 4 to 6 weeks on the immediate-release tablet. what is the evidence for the formulation and the duration i am actually on?
  • if bupropion is being added to another antidepressant, is that drug on the cyp2d6 list, and does its dose need reviewing?
  • i have lost weight or appetite since starting. is that the drug, and does it matter for me?
  • if i ever want to stop, how would we do it, and how would we tell a return of symptoms from the change itself?

questions people ask

does bupropion have a black box warning?
yes. the fda label carries one boxed warning, on suicidal thoughts and behaviors in children, adolescents and young adults in short-term trials. the label states the trials showed no increase above age 24 and a reduction at 65 and older. per 1,000 people treated, the pooled numbers are 14 additional cases under 18, 5 additional at 18 to 24, 1 fewer at 25 to 64 and 6 fewer at 65 and over. the separate boxed warning once carried by the quit-smoking products was removed after the eagles trial.
what is the seizure risk with bupropion?
the label says the risk is dose-related: about 0.1% (1 in 1,000) at doses up to 300 mg a day and about 0.4% (4 in 1,000) at the maximum 400 mg a day. it is contraindicated in anyone with a seizure disorder, a current or past diagnosis of anorexia nervosa or bulimia, or who is abruptly stopping alcohol, benzodiazepines, barbiturates or antiepileptic drugs, and other drugs that lower the seizure threshold add to the risk.
what are the most common bupropion side effects?
from the label’s trials at 300 mg a day (376 people) against placebo (385): headache 26% vs 23%, dry mouth 17% vs 7%, nausea 13% vs 8%, insomnia 11% vs 6%, constipation 10% vs 7%, dizziness 7% vs 5%, tremor 6% vs 1%, sweating 6% vs 2%, ringing in the ears 6% vs 2%, loss of appetite 5% vs 2%. rash was the most common reason for leaving the trials, 2.4% vs 0%.
does bupropion cause weight loss or sexual side effects?
weight: in the label’s trials 14% of people on 300 mg and 19% on 400 mg lost more than 5 pounds against 6% on placebo, and fewer gained. sexual: the label lists decreased libido and impotence only as infrequent reactions, and in pooled trials bupropion caused no more sexual dysfunction than placebo while ssris caused significantly more. a cochrane review found adding bupropion 150 mg twice a day improved ssri-induced sexual dysfunction more than placebo.
does bupropion raise blood pressure?
the label says it can, asks for a blood pressure check before starting and periodically after, and reports treatment-emergent hypertension in 6.1% of people on bupropion plus a nicotine patch against 2.5% on bupropion alone and 3.1% on placebo in a quit-smoking trial, mostly in people who already had high blood pressure.

sources for this section

the library rows link to our one-page summary of each study, with the original paper, its funding and our evidence grade on that page.

  1. bupropion hydrochloride extended-release tablets (sr) prescribing information, fda label on dailymed (set id 0aa86bd6-b37b-45f7-a837-b067e41184e9, version 4, effective august 27, 2026): boxed warning; sections 4, 5.1 to 5.8, 6.1 tables 2 to 4, 9, 14 table 6
  2. ahrq medical expenditure panel survey, prescribed medicines public-use file 2024 (hc-254a): people with at least one bupropion purchase, weighted; computed by veisund, method on the usage section of this page
  3. the antidepressant suicidality warning has an age ceiling most people never hear about (fda boxed warning, read off the label) (library row)
  4. bupropion raises the level of other antidepressants, antipsychotics and beta blockers by blocking cyp2d6 (wellbutrin xl prescribing information, drug interactions, february 2026) (library row)
  5. cipriani a, et al. comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder. lancet 2018 (library row)
  6. thase me, et al. remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis. journal of clinical psychiatry 2005 (library row)
  7. serretti a, chiesa a. treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. journal of clinical psychopharmacology 2009 (library row)
  8. hajizadeh a, et al. antidepressants for smoking cessation. cochrane database of systematic reviews 2023 (library row)
  9. taylor mj, et al. strategies for managing sexual dysfunction induced by antidepressant medication. cochrane database of systematic reviews 2013 (library row)
  10. mohamed s, et al. effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder (vast-d). jama 2017 (library row)
  11. rush aj, et al. bupropion-sr, sertraline, or venlafaxine-xr after failure of ssris for depression (star*d). new england journal of medicine 2006 (library row)
  12. anthenelli rm, et al. neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (eagles). lancet 2016. industry funded (library row)
we went and looked

claims about bupropion we went and checked

every check quotes one sentence, links the original at the timestamp, and takes each assertion to the primary record. the full list: /checked.

How long the bupropion trials actually ran

The longest trial behind the bupropion approval ran 6 weeks.

The gap between how long the trials ran and how long people actually take these medications is the single most important thing on this page. It is not evidence that longer use is unsafe or ineffective. It is evidence that longer use was not what got tested.

People often stay on these drugs for far longer than the trials ran. The trials behind the approval ran 4 to 6 weeks.

That does not mean longer use is unsafe. It does not mean the drug stops working either. It means longer use was never the thing that got tested.

If you have been on it a long time, that is a fair thing to ask your prescriber about.

Boxed warning: suicidal thoughts and behaviors

The strongest warning the FDA puts on a label, often called a black box warning. It is reproduced below word for word, not summarised.

This is the strongest warning the FDA can put on a drug label. Some people call it a black box warning. We copied it word for word. We did not shorten it and we did not soften it.

The warning below is about suicidal thoughts. In short studies, antidepressants raised the risk of suicidal thoughts and behavior. That was in children, teens, and young adults. The same studies did not show that added risk in people over 24. In people aged 65 and older the risk went down. The label tells prescribers to watch every patient closely when treatment starts.

The FDA’s own words follow, copied exactly.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS SUICIDALITY AND ANTIDEPRESSANT DRUGS Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in subjects over age 24; there was a reduction in risk with antidepressant use in subjects aged 65 and older [see Warnings and Precautions (5.1) ] . In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber [see Warnings and Precautions (5.1) ]. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. • Increased risk of suicidal thinking and behavior in children, adolescents and young adults taking antidepressants. ( 5.1 ) • Monitor for worsening and emergence of suicidal thoughts and behaviors. ( 5.1)

FDA label effective August 27, 2026 — read the full label on DailyMed

What bupropion is FDA approved for, and the trials behind it

Approved for the treatment of major depressive disorder; this anchor is the 1996 sustained-release formulation, whose efficacy rests on trials of the earlier immediate-release form in 1996, under application NDA 020358. Source: FDA Drugs@FDA.

The label does not state the total number of patients across the three efficacy trials, only the per-arm counts in its efficacy table, and it does not describe the immediate-release formulation's own earlier approval history.

The trials behind bupropion's depression indication used the immediate-release formulation: two 4-week placebo-controlled trials in adult inpatients and one 6-week placebo-controlled trial in adult outpatients, with drug arms of 34 to 110 patients at 300 to 600 mg per day. The sustained-release form approved under this application was accepted on bioequivalence to the immediate-release form. A separate placebo-controlled trial showed the sustained-release form maintained antidepressant response for up to 44 weeks after 8 weeks of acute treatment.

Two gaps first. The label does not give a total number of patients across the three trials. It gives only the count in each arm of its results table. It also says nothing about the fast-release form’s own approval history.

The FDA approved bupropion in 1996. The approved use was major depression. This record covers the 1996 slow-release form. Its proof of benefit rests on trials of the earlier fast-release form. The file number is NDA 020358. The source is Drugs@FDA, the FDA's own database.

The trials behind the depression use tested the fast-release form. Two ran 4 weeks in adults in hospital, against a placebo. One ran 6 weeks in adults seen as outpatients, against a placebo.

The drug arms held 34 to 110 patients each. Doses ran from 300 to 600 mg a day.

The slow-release form approved here was not tested again. It was accepted because it puts the same amount of drug into the body. The label calls that bioequivalence.

A separate trial against a placebo followed people for longer. It showed the slow-release form held the benefit for up to 44 weeks after 8 weeks of first treatment.

Trials
3 placebo-controlled trials (immediate-release form)
Duration
4 to 6 weeks
Participants
Drug arms of 34 to 110 patients
Compared against
Placebo
Although there are not as yet independent trials demonstrating the antidepressant effectiveness of the sustained-release formulation of bupropion, trials have demonstrated the bioequivalence of the immediate-release and sustained-release forms of bupropion under steady-state conditions, i.e., bupropion sustained-release 150 mg twice daily was shown to be bioequivalent to 100 mg 3 times daily of the immediate-release formulation of bupropion, with regard to both rate and extent of absorption, for parent drug and metabolites.

Verbatim from the bupropion FDA label, Clinical Studies section, effective August 27, 2026 — read the full label on DailyMed.

Side effects of bupropion in the approval trials

Incidence at 300 mg per day of the sustained-release form (376 subjects) versus placebo (385 subjects) in placebo-controlled depression trials; the label also reports a 400 mg per day group of 114 subjects with generally higher rates. The label itself cautions that trial adverse-reaction rates may not reflect the rates observed in clinical practice.

Read the limits first. These numbers come from depression trials against a placebo. The dose was 300 mg a day of the slow-release form. 376 people took the drug and 385 took a placebo.

The label also reports a group of 114 people at 400 mg a day. Most rates were higher there. It warns that real life may not match trial rates.

  • Headache (26% vs 23% on placebo)
  • Dry mouth (17% vs 7%)
  • Nausea (13% vs 8%)
  • Insomnia (11% vs 6%)
  • Constipation (10% vs 7%)
  • Dizziness (7% vs 5%)
  • Tremor (6% vs 1%)
  • Sweating (6% vs 2%)
  • Tinnitus (6% vs 2%)
  • Anorexia (5% vs 2%)
Most common adverse reactions (incidence ≥5% and ≥2% more than placebo rate) are: headache, dry mouth, nausea, insomnia, dizziness, pharyngitis, constipation, agitation, anxiety, abdominal pain, tinnitus, tremor, palpitation, myalgia, sweating, rash, and anorexia.

From the bupropion FDA label, Adverse Reactions section, effective August 27, 2026 — DailyMed.

More from the bupropion label: drug abuse and dependence

  • Not a controlled substance, with stimulant-like findings on record

    Bupropion is not scheduled under the Controlled Substances Act. The label reports that a single 400 mg oral dose produced mild amphetamine-like activity in people experienced with drugs of abuse, that the recommended divided dosing is not likely to be significantly reinforcing, and that seizures and deaths have been reported when bupropion was inhaled as crushed tablets or injected.

    FDA label, Drug Abuse and Dependence section.

  • Dose-related seizure risk

    The label states bupropion can cause seizure and the risk is dose-related: approximately 0.1% at doses up to 300 mg per day, rising to approximately 0.4% at the maximum recommended 400 mg per day. It is contraindicated in patients with a seizure disorder, a current or prior diagnosis of anorexia nervosa or bulimia, or abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.

    FDA label, Warnings and Precautions section.

How many Americans take bupropion

Survey-based federal estimates, published with a lag of about two years. They count prescriptions filled, not outcomes.

These are federal survey numbers. They come out about two years late. They count prescriptions filled. They do not tell you if the drug helped.

34,914,025
prescriptions in the United States (2024), refills included
8,042,018
people filling them (2024), ± 850,371 (95%)

Prescriptions are up 39% from 2014 to 2024, a change larger than the survey’s margin of error. Whatever you decide about bupropion, you are deciding alongside about 8,042,018 other people in 2024.

Prescriptions by year: 2014 25,051,661 · 2015 26,198,463 · 2016 23,811,613 · 2017 24,903,971 · 2018 24,488,844 · 2019 25,722,873 · 2020 28,889,369 · 2021 29,099,445 · 2022 25,197,923 · 2023 30,349,391 · 2024 34,914,025.

Prescriptions are up 39 percent since 2014. About 8.0 million people in the United States took it in 2024.

Correction (29 September 2026). An earlier version of this section took its numbers from ClinCalc DrugStats, a third-party site that republishes this survey; we now compute them from AHRQ’s public-use files ourselves. It showed 8,042,017 people and 34,895,515 prescriptions for 2024; the file gives 8,042,018 and 34,914,025.

Source: AHRQ Medical Expenditure Panel Survey (MEPS), Prescribed Medicines public-use files, 2014 (HC-168A) through 2024 (HC-254A), computed by veisund. People with at least one purchase where the Multum generic name (RXDRGNAM) equals the drug, weighted by the year’s person weight; purchases include refills. Standard errors by Taylor linearization on VARSTR/VARPSU. AHRQ’s reliability rule: a year is not shown when fewer than 60 survey respondents reported the drug or the relative standard error is over 50%. AHRQ cautions that its 2018 questionnaire redesign and the 2020–2022 pandemic years make year-to-year comparisons less certain.

What people report to the FDA about bupropion

Read this before the numbers.

Anyone can file an adverse event report — patients, doctors, manufacturers — and nobody verifies that the drug caused what was reported. There is no denominator: tens of millions of prescriptions generate reports at an unknowable rate, and reporting rises with news coverage, not necessarily with harm. Counts below are report volumes, not rates, and cannot be compared between drugs. The FDA itself says not to use this data to make medical decisions — we show it because you deserve to see what is in the public record, with its limits stated plainly.

Read this before the numbers.

Anyone can send a report to the FDA. Patients can. Doctors can. Drug makers can. Nobody checks that the drug caused what the report describes.

There is also no bottom number. Tens of millions of prescriptions turn into reports at a rate nobody knows. Reports go up when a drug is in the news, and that is not the same as more harm.

So these are counts of reports. They are not rates. You cannot use them to compare one drug with another. The FDA itself says not to use this data to make medical choices.

We show it because it is on the public record, and you should get to see it with its limits named.

152,137
reports mentioning bupropion, all time
83,540
filed as serious (a report-level flag covering every drug and outcome in the report)
filed as serious. That flag covers the whole report, and one report can name more than one drug and more than one outcome.

Most-reported reactions

  • Drug ineffective13,176
  • Nausea11,909
  • Fatigue10,076
  • Headache10,053
  • Depression8,639
  • Dizziness7,786
  • Anxiety7,785
  • Pain6,854
  • Off label use6,645
  • Completed suicide5,993

“Drug ineffective” ranking this high is worth noticing: a report of not being helped counts as an adverse event too, and people file them in large numbers.

It is worth noticing how high “drug ineffective” ranks. A report that the drug did not help counts as an adverse event too. People file a lot of them.

Source: FDA Adverse Event Reporting System (FAERS), via openFDA, openFDA dataset refreshed 2026-07-30 (the refresh date of the query endpoint, not the date reports run through).

Drug interactions listed on the bupropion label

The FDA label’s interactions section, verbatim. A pharmacist checking your actual medication list beats any published list — including this one.

Below is the part of the FDA label that lists other drugs. It is copied word for word.

No list on the web can see what else you take. A pharmacist can. Ask one to check your full list.

Read the label’s interactions section

7 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 response, but should not exceed the maximum recommended dose. ( 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). Consider dose reduction when using with bupropion. ( 7.2 ) • Digoxin: May decrease plasma digoxin levels. Monitor digoxin levels. ( 7.2 ) • Drugs that lower seizure threshold: Dose bupropion hydrochloride extended-release tablets (SR) with caution. ( 5.3 , 7.3 ) • Dopaminergic drugs (levodopa and amantadine): CNS toxicity can occur when used concomitantly with bupropion hydrochloride extended-release tablets (SR). ( 7.4 ) • MAOIs: Increased risk of hypertensive reactions can occur when used concomitantly with bupropion hydrochloride extended-release tablets (SR). ( 7.6 ) • Drug-laboratory test interactions: Bupropion hydrochloride extended-release tablets (SR) can cause false-positive urine test results for amphetamines. ( 7.7 )

7.1 Potential for Other Drugs to Affect Bupropion Hydrochloride Extended-Release Tablets (SR) Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between bupropion hydrochloride extended-release tablets (SR) and drugs that are inhibitors or inducers of CYP2B6. Inhibitors of CYP2B6 Ticlopidine and Clopidogrel : Concomitant treatment with these drugs can increase bupropion exposure but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of bupropion hydrochloride extended-release tablets (SR) may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology (12.3) ] . Inducers of CYP2B6 Ritonavir, Lopinavir, and Efavirenz : Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of bupropion hydrochloride extended-release tablets (SR) may be necessary when coadministered with ritonavir, lopinavir, or efavirenz [see Clinical Pharmacology (12.3) ] but should not exceed the maximum recommended dose. Carbamazepine, Phenobarbital, Phenytoin : While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure [see Clinical Pharmacology (12.3) ] . If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded.

7.2 Potential for Bupropion Hydrochloride Extended-Release Tablets (SR) to Affect Other Drugs Drugs Metabolized by CYP2D6 Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of bupropion hydrochloride extended-release tablets (SR) with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone and flecainide). When used concomitantly with bupropion hydrochloride extended-release tablets (SR), it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index. Drugs that require metabolic activation by CYP2D6 to be effective (e.g., tamoxifen) theoretically could have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion. Patients treated concomitantly with bupropion hydrochloride extended-release tablets (SR) and such drugs may require increased doses of the drug [see Clinical Pharmacology (12.3) ]. Digoxin Coadministration of bupropion hydrochloride extended-release tablets (SR) with digoxin may decrease plasma digoxin levels. Monitor plasma digoxin levels in patients treated concomitantly with bupropion hydrochloride extended-release tablets (SR) and digoxin [see Clinical Pharmacology (12.3) ] .

7.3 Drugs that Lower Seizure Threshold Use extreme caution when coadministering bupropion hydrochloride extended-release tablets (SR) with other drugs that lower seizure threshold (e.g., other bupropion products, antipsychotics, antidepressants, theophylline, or systemic corticosteroids). Use low initial doses and increase the dose gradually [see Contraindications (4) , Warnings and Precautions (5.3) ].

7.4 Dopaminergic Drugs (Levodopa and Amantadine) Bupropion, levodopa, and amantadine have dopamine agonist effects. CNS toxicity has been reported when bupropion was coadministered with levodopa or amantadine. Adverse reactions have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. It is presumed that the toxicity results from cumulative dopamine agonist effects. Use caution when administering bupropion hydrochloride extended-release tablets (SR) concomitantly with these drugs.

7.5 Use with Alcohol In postmarketing experience, there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with bupropion hydrochloride extended-release tablets (SR). The consumption of alcohol during treatment with bupropion hydrochloride extended-release tablets (SR) should be minimized or avoided.

7.6 MAO Inhibitors Bupropion inhibits the reuptake of dopamine and norepinephrine. Concomitant use of MAOIs and bupropion is contraindicated because there is an increased risk of hypertensive reactions if bupropion is used concomitantly with MAOIs. Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAO inhibitor phenelzine. At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of treatment with bupropion hydrochloride extended-release tablets (SR). Conversely, at least 14 days should be allowed after stopping bupropion hydrochloride extended-release tablets (SR) before starting an MAOI antidepressant [see Dosage and Administration (2.4 , 2.5 ), Contraindications (4) ].

7.7 Drug-Laboratory Test Interactions False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. This is due to lack of specificity of some screening tests. False-positive test results may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.

FDA label for bupropion, effective August 27, 2026 — DailyMed.

Label history: when this label changes, it is recorded in What changed.

Who pays for bupropion

Two claims datasets and one survey, covering different populations with different instruments — they cannot be reconciled by arithmetic, and where their sum crowds the all-payer estimate, that is a finding about the estimates rather than a percentage.

Medicare Part D · claims · 2024Medicaid · claims floor · 2024All-payer · survey · 2024Commercially insured adults · not publishedChildren · no per-drug data
Medicare Part D
Read the under-65 group correctly before the numbers: Medicare before 65 means the disabled and dual-eligible population — among the sickest, highest-need people in the program — and reading their utilization as typical adult use would be a category error. The beneficiary total sums brand-level rows, so treat it as an upper bound on distinct people. 2,224,023 beneficiaries filled 9,811,789 claims in 2024 — 1,692,577 aged 65 and over, and 531,446 under 65.
Medicaid
At least 6,860,093 prescriptions in 2024 — a floor, because 333 of 1,765 national data rows are suppressed for privacy and contribute zero. Medicaid covers more children than any insurer in the country and publishes no age split — how much of this number is pediatric use is not knowable from public data.
All payers (survey estimate)
A survey estimate from 471 respondents, which we computed from AHRQ’s MEPS 2024 Prescribed Medicines file (people with at least one purchase, weighted; purchases include refills), puts the whole country at 34,914,025 purchases and 8,042,018 people in 2024. Subtracting the public programs from it would produce a number for everyone else — and we do not print that number, because subtracting a survey from claims counts manufactures precision that does not exist.
The population nobody counts
The commercially insured working-age adult — statistically, the likeliest person to be reading this page — is the one population with no public per-drug count anywhere. Private claims data exists and is sold, but nothing a patient can check is published. For children the record is thinner still: no public source counts pediatric use of bupropion specifically; the closest the public record comes is condition-level treatment rates for children, which we have traced for one condition in how childhood ADHD got counted.

Sources: Medicare Part D Prescribers — by Geography and Drug, data.cms.gov, National rows, data year 2024 (published with ~17-month lag). Medicaid State Drug Utilization Data 2024, data.medicaid.gov, national aggregate rows. Retrieved 2026-09-01.

Who has been paying for bupropion, 2019–2024

Medicare Part D

Claims, all ages — the one payer with a public per-drug series.

20192024

7,886,797 → 9,811,789 claims

Medicare under 65

Beneficiaries, not ordinary working-age adults: Medicare before 65 means the disabled and dual-eligible population. A gap is a suppressed split, not zero.

20192024

576,227 → 531,446 beneficiaries

Medicaid

A floor each year — small-cell rows are suppressed federally and excluded from the sum.

20192024

5,851,040 → 6,860,093 prescriptions (floor)

Commercially insured adults

No public dataset publishes per-drug commercial claims for any year — the absence is the finding, and it is rendered, not interpolated. The population this library most wants to inform is the one with no public per-drug series, in any year — insurers and PBMs hold that data privately. What the federal surveys do measure — how many adults take these medications at all — is on the adult-usage page.

Sources: Medicare Part D Prescribers by Geography and Drug (data.cms.gov, national rows, per data year); Medicaid State Drug Utilization Data (data.medicaid.gov, national rows). Claims, fills and beneficiaries are different units — compare each series only with itself.

The bupropion approval, step by step

  1. Step 1

    What the approval was actually based on

    Which studies did the FDA rely on, how long did they run, and who was in them?

    The efficacy of the immediate-release formulation of bupropion in the treatment of major depressive disorder was established in two 4-week, placebo-controlled trials in adult inpatients with MDD (Trials 1 and 2 in Table 6) and in one 6-week, placebo-controlled trial in adult outpatients with MDD (Trial 3 in Table 6).

    FDA-approved labelling, 14 CLINICAL STUDIES — read the label on DailyMed

    Our reading

    Three trials, and every one of them in a formulation almost nobody is prescribed now. Sustained- and extended-release bupropion were bridged to these results on pharmacokinetic grounds rather than re-proven on their own efficacy evidence. The trials were also very small — Trial 1 randomised 48 people to bupropion and 27 to placebo — and Trial 2 only separated from placebo at 450 mg/day, above the dose most people take.

  2. Step 2

    The approval

    When was it approved, under what application, and by whose review?

    Approved
    October 4, 1996
    Application
    NDA020358
    Review
    STANDARD
    Original sponsor
    GlaxoSmithKline
    Holds it now
    GlaxoSmithKline
    Label submissions since
    60

    Source: openFDA Drugs@FDA, original application ORIG-1

  3. Step 3

    What was added after it was on the market

    Which warnings arrived only after millions of people were already taking it?

    • Bupropion raises the level of other antidepressants, antipsychotics and beta blockers by blocking CYP2D6

      30 years after approval

      Bupropion is often added to another antidepressant, which is exactly the situation its interaction section is about.

      Significant findings

      WELLBUTRIN XL prescribing information (Bausch Health, February 2026), Drug Interactions summary: "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). Consider dose reduction when using with bupropion."

      The other direction: "CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin)".

      Three more lines from the same summary: "Drugs that lower seizure threshold: Dose Wellbutrin XL with caution." "Dopaminergic Drugs (levodopa and amantadine): CNS toxicity can occur when used concomitantly". "MAOIs: Increased risk of hypertensive reactions can occur when used concomitantly with Wellbutrin XL."

      And one that is not a drug interaction but is worth knowing: "False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion."

      Worth asking

      The combination of bupropion with an SSRI or SNRI is common and often sensible; the label does not forbid it, it asks for a dose review of the other drug. The seizure line is the one to take seriously if you are also on tramadol, a stimulant or an antipsychotic, or drink heavily. If bupropion is being added to your regimen, the questions are whether any of your other drugs is on the CYP2D6 list and whether anything else you take lowers the seizure threshold.

      WELLBUTRIN XL (bupropion hydrochloride) extended-release tablets: FDA-approved prescribing information, Drug Interactions 7.1 to 7.7 — Bausch Health US LLC; US Food and Drug Administration (2026)

    • The antidepressant suicidality warning has an age ceiling most people never hear about

      Antidepressants carry a boxed warning about suicidal thoughts and behaviour in children, adolescents and young adults. It came from pooling 24 short-term placebo-controlled trials of nine antidepressants in more than 4,400 young patients: suicidality was reported in about 4% on drug against 2% on placebo. There were no completed suicides in those trials.

      The part that usually gets lost is the age boundary, which is in the label itself. The studies did not show an increased risk above age 24, and in patients 65 and older the risk went in the other direction — it was reduced. The warning is real and it is specific, not a blanket statement about everyone who takes one.

      Worth asking

      Given my age, which side of that line am I on, what specifically should I or the people around me watch for in the first two months, and who do I call if it happens.

      PROZAC (fluoxetine) prescribing information — Boxed Warning: Suicidal Thoughts and Behaviors — U.S. Food and Drug Administration (approved labelling)

  4. Step 4

    What independent research has found since

    What has been learned by people who were not selling it?

  5. Step 5

    What still is not known

    Which questions you might reasonably have has nobody answered yet?

    • The efficacy evidence is for immediate-release in inpatients over four to six weeks. Most prescriptions today are XL, outpatient, and long-term.
    • Trial 2 demonstrated effectiveness only at 450 mg/day. What does that imply about the dose you are on?
    • What is the long-term evidence for the formulation you are actually taking?
    • Seizure risk was the historical concern that shaped the dosing. Does your dose and history account for it?

The bupropion legal and safety record

Settled and adjudicated matters only, from primary sources — including the litigation that was decided for the manufacturer, and the cases this drug is verifiably not part of.

Read the bupropion legal and safety record

Deciding about bupropion?

Open bupropion (Wellbutrin SR) in veisund

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