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Research · Medication

Bupropion

Pooled trials found bupropion raised depression response to 62% against 51% on placebo, level with SSRIs, and Cochrane reviews found about 3 extra quitters per 100 smokers and fewer winter depression episodes. Sexual side effects matched placebo. Insomnia and dry mouth were common, and seizures occurred in about 1 in 1,000 at standard doses.

Add to Bio HackChecked 2026-11-13
Status
Prescription drug in the US. FDA-approved for major depressive disorder, for prevention of seasonal affective disorder (extended-release form) and as an aid to smoking cessation (sustained-release form). It is not approved for ADHD, weight loss on its own or sexual side effects of other antidepressants.
Also called
bupropion hydrochloride, Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban, bupropion SR, bupropion XL, aminoketone antidepressant
Taken for
depression, quitting smoking, seasonal depression, winter blues, ADHD, weight loss, sexual side effects of SSRIs, adding to another antidepressant

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help6

Reported risks19

What people take it for, and what was found

Shown to help6

StrongVery common

Depression in adults

Shown to raise response in adult depression, 62% against 51% on placebo in seven pooled trials, level with SSRIs.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In original data from seven trials, response was 62% on bupropion, 63% on SSRIs and 51% on placebo, and remission was 47%, 47% and 36% [1]. Across 522 trials of 21 antidepressants that included bupropion, every drug had a higher response rate than placebo, with odds ratios from 1.37 to 2.13 [2]. A systematic review of 51 studies found the more robust trials favored bupropion over placebo and most head-to-head trials showed effects equal to other antidepressants [3].
Population
Adults with major depression in 7 randomized trials comparing bupropion, SSRIs and placebo [1]; 116,477 adults in 522 trials [2]; 51 studies of bupropion as an antidepressant [3].
Sources
[1], [2], [3]
Caveats
Smaller and older studies of bupropion showed larger effects against placebo [2]. The evidence is thinner in people with a first episode who have never been treated [3]. Most trials lasted weeks.
StrongCommon

Quitting smoking

Shown to raise smoking quit rates about 1.6 times over placebo, roughly 3 extra quitters per 100, and less than varenicline did.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Bupropion raised quit rates against placebo or no drug (RR 1.60, 95% CI 1.49 to 1.72, 50 studies) [4]. In a network meta-analysis the odds ratio against control was 1.43 (95% CrI 1.26 to 1.62), which the authors put at 3 additional quitters per 100 (95% CrI 2 to 4) [5]. In a trial of 8,144 smokers, abstinence was more likely on bupropion than placebo (OR 2.07, 95% CI 1.75 to 2.45) and more likely on varenicline than bupropion (OR 1.75, 95% CI 1.52 to 2.01) [6]. Quit rates on bupropion were lower than on varenicline (RR 0.73, 95% CI 0.67 to 0.80) and similar to single-form nicotine replacement (RR 1.03, 95% CI 0.93 to 1.13) [4].
Population
18,577 participants in 50 studies, mostly adults from the community or cessation clinics [4]; 14,759 participants in 71 RCTs of bupropion within a 319-trial network [5]; 8,144 smokers with and without psychiatric disorders [6].
Sources
[4], [5], [6]
Caveats
Both reviews rated the bupropion evidence high certainty. 118 of the trials in the network reported drug or tobacco industry funding [5].
ModerateVery common

Preventing winter depression

Shown to lower new episodes of seasonal depression in adults with a history of it, with 84% staying depression-free against 72% on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Started in autumn before symptoms and continued to spring, extended-release bupropion lowered the risk of a depressive episode (RR 0.56, 95% CI 0.44 to 0.72). The number needed to treat was 8 where the yearly recurrence rate is 30% and 4 where it is 60%. Headache, insomnia and nausea were more frequent than on placebo [7]. Across the three trials, 84.3% on bupropion and 72.0% on placebo stayed free of a depressive episode [8].
Population
1,100 adults with a history of seasonal affective disorder in 3 RCTs [7][8].
Sources
[7], [8]
Caveats
All three trials had high dropout, and the review rated the evidence moderate quality. The review found no trials comparing bupropion with light therapy or psychological therapy [7].
Moderate

ADHD

Shown to reduce ADHD symptoms in adults by a moderate amount in a Cochrane review of six small trials rated low quality. Not an approved use.

The numbers and sources
Effect
Long-acting bupropion lowered the severity of ADHD symptoms against placebo (SMD -0.50, 95% CI -0.86 to -0.15, 3 studies, 129 participants) and raised the share with clinical improvement (RR 1.50, 95% CI 1.13 to 1.99). Withdrawal for adverse effects was similar to placebo (RR 1.20, 95% CI 0.35 to 4.10) [12]. In children and adolescents, three head-to-head trials found bupropion comparable to methylphenidate, while a large placebo-controlled study found smaller effects than methylphenidate [13].
Population
438 adults in 6 studies of 6 to 10 weeks [12]; open and randomized trials in children and adolescents [13].
Sources
[12], [13]
Caveats
Four of six adult studies were industry funded, none was judged free of bias, and samples were small [12]. The pediatric review calls its database very limited [13].
Moderate

Weight loss

Shown to produce about 2.8 kg more weight loss than placebo over 6 to 12 months in obesity trials. Not approved alone for this use.

The numbers and sources
Effect
In a meta-analysis of obesity drug trials, bupropion produced 2.77 kg more weight loss than placebo at 6 to 12 months (95% CI 1.1 to 4.5) when given alongside diet advice [14]. In depression trials, 14% on 300 mg a day and 19% on 400 mg a day lost more than 5 pounds, against 6% on placebo [15]. A meta-analysis of antidepressants and body weight found some weight loss with bupropion [16].
Population
Adults in randomized obesity trials [14]; 451 adults on sustained-release bupropion and 347 on placebo in depression trials [15]; antidepressant trials reporting weight [16].
Sources
[14], [15], [16]
Caveats
Heterogeneity was present in every analysis in [14], and long-term health outcomes were not measured. The combination of bupropion with naltrexone is covered on its own page.
Moderate

Sexual side effects from other antidepressants

Shown to improve sexual function scores in people with antidepressant-related sexual problems at 150 mg twice daily in three trials, and not at 150 mg once daily.

The numbers and sources
Effect
In three studies in men and women, adding bupropion 150 mg twice daily improved sexual function rating scores against placebo (SMD 1.60, 95% CI 1.40 to 1.81). In two studies of 150 mg once daily, response rates did not differ from placebo (RR 0.62, 95% CI 0.09 to 4.41) [17].
Population
People with sexual dysfunction on antidepressants, within a Cochrane review of 23 trials and 1,886 participants [17].
Sources
[17]
Caveats
Not an approved use. Few trials, with the benefit seen only at the higher dose [17].

Mixed results1

Moderate

Added to another antidepressant

Mixed results: remission was 27% to 30% when bupropion was added to an antidepressant in three large trials, none with a placebo arm.

The numbers and sources
Effect
After citalopram alone had not brought remission, adding sustained-release bupropion gave a remission rate of 29.7% and adding buspirone 30.1%. Bupropion lowered self-rated symptom scores more (25.3% vs 17.1%) and fewer people stopped it for intolerance (12.5% vs 20.6%) [9]. In US veterans, remission at 12 weeks was 26.9% with added bupropion, 28.9% with added aripiprazole and 22.3% after a switch to bupropion, and the bupropion comparisons were not significant [10]. In adults 60 and older, remission was 28.2% with added bupropion, 28.9% with added aripiprazole and 19.3% after a switch to bupropion [11].
Population
Adults whose depression had not remitted on citalopram [9]; 1,522 veterans, 85% men, mean age 54 [10]; 619 adults aged 60 and older with treatment-resistant depression [11].
Sources
[9], [10], [11]
Caveats
No trial here compared added bupropion with added placebo, so the share of remission due to bupropion is unknown. The abstract of [9] does not give the number randomized.

Doses studied

The extended-release label lists 150 mg once daily to start and 300 mg once daily as the target for depression, and the seasonal depression trials reached mean doses of 257 to 280 mg a day [8]. The depression trials of the sustained-release form compared 300 and 400 mg a day with placebo [15]. The smoking cessation trials tested 100, 150 and 300 mg a day for 7 weeks alongside counseling [18].

The adult ADHD trials used 150 to 450 mg a day of a long-acting form [12]. The trials for antidepressant-related sexual problems used 150 mg once or twice daily [17]. The label ties seizure risk to dose, with the reported incidence rising above 450 mg a day of the immediate-release form [8].

Risks

Reported risks18

ModerateVery common

Insomnia

Shown to raise insomnia, in 11% to 16% against 6% on placebo in depression trials. Drowsiness was no more frequent than on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In depression trials of the sustained-release form, insomnia occurred in 11% at 300 mg a day and 16% at 400 mg a day against 6% on placebo, and somnolence in 2% and 3% against 2% [15]. In seasonal depression trials, insomnia occurred in 20% against 13% on placebo [8]. In a smoking cessation trial, insomnia was the most frequent adverse event on bupropion, at 12% [6]. A meta-analysis of second-generation antidepressants found the highest incidence of insomnia with bupropion and desvenlafaxine, and less somnolence on bupropion than on placebo [21].
Population
490 adults on sustained-release bupropion and 385 on placebo [15]; 537 on extended-release bupropion and 511 on placebo [8]; 2,006 smokers assigned to bupropion [6]; trials of second-generation antidepressants in depression [21].
Sources
[15], [8], [6], [21]
Caveats
Short-term trials. The rate rose with dose [15].
ModerateVery common

Dry mouth, nausea and other common side effects

Shown to raise dry mouth, nausea, dizziness, tremor, sweating and ringing in the ears against placebo, with dry mouth in 17% to 24% against 7%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In depression trials at 300 and 400 mg a day against placebo: dry mouth 17% and 24% vs 7%, nausea 13% and 18% vs 8%, dizziness 7% and 11% vs 5%, tremor 6% and 3% vs 1%, sweating 6% and 5% vs 2%, tinnitus 6% and 6% vs 2%, anxiety 5% and 6% vs 3% and agitation 3% and 9% vs 2% [15]. In smoking cessation trials, more people dropped out for adverse events on bupropion than on placebo (RR 1.44, 95% CI 1.27 to 1.65) [4]. In veterans with depression, anxiety was reported by 22.5% to 24.3% in the bupropion groups against 16.6% on added aripiprazole [10].
Population
490 adults on sustained-release bupropion and 385 on placebo [15]; 12,346 participants in 25 smoking cessation studies [4]; 1,522 veterans [10].
Sources
[15], [4], [10]
Caveats
Short-term trials. Several effects were more frequent at 400 mg than at 300 mg a day [15].
ModerateVery common

Weight change

Shown to cause weight loss more often than placebo: 14% to 19% lost more than 5 pounds in depression trials against 6% on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In depression trials, 14% on 300 mg a day and 19% on 400 mg a day lost more than 5 pounds against 6% on placebo, and 3% and 2% gained more than 5 pounds against 4% [15]. In seasonal depression trials lasting up to 6 months, 23% lost more than 5 pounds against 11% on placebo, and 11% gained that much against 21% [8]. In health records, estimated 6-month weight gain was 0.22 kg lower than on sertraline (95% CI 0.12 to 0.33), with a 15% lower risk of gaining 5% of baseline weight [22].
Population
Adults in placebo-controlled depression and seasonal depression trials [15][8]; adults starting one of 8 antidepressants in US health systems [22].
Sources
[15], [8], [22]
Caveats
The label notes weight loss may be unwanted where it is already a sign of a person's depression [15]. [22] is observational and compared drugs with each other.
ModerateCommon

FDA boxed warning: suicidal thoughts and behaviors in young people

FDA states antidepressants raised suicidal thoughts and behaviors in children, adolescents and young adults in short-term trials, 14 more cases per 1,000 under age 18.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
The bupropion label carries the antidepressant boxed warning. In FDA's pooled analyses of placebo-controlled antidepressant trials, the difference between drug and placebo in cases of suicidal thoughts or behaviors per 1,000 patients treated was 14 more under age 18, 5 more at ages 18 to 24, 1 fewer at ages 25 to 64 and 6 fewer at 65 and older. No suicides occurred in the pediatric trials [8]. In the pediatric analysis, the risk ratio for all antidepressants across all indications was 1.95 (95% CI 1.28 to 2.98), a risk difference of 0.02 [19]. In adults with psychiatric indications, the odds ratio for suicidal behavior or ideation was 1.62 (95% CI 0.97 to 2.71) under age 25, 0.79 (95% CI 0.64 to 0.98) at 25 to 64 and 0.37 (95% CI 0.18 to 0.76) at 65 and older [20].
Population
Placebo-controlled trials of antidepressants in adults and pediatric patients pooled by FDA [8][19][20].
Sources
[8], [19], [20]
Caveats
The pooled analyses cover antidepressants as a group, not bupropion alone. The label reports differences from placebo, not absolute rates, so the band above is the excess under age 18. The trials were short.
ModerateCommon

Raised blood pressure

Shown to raise blood pressure by about 1 mm Hg on average. New hypertension was more frequent when bupropion was combined with a nicotine patch.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Across randomized trials, bupropion alone or with naltrexone raised systolic pressure by 1.34 mm Hg (95% CI 0.38 to 2.29) and diastolic by 0.93 mm Hg (95% CI 0.88 to 0.99), more at doses above 360 mg [24]. In a smoking cessation trial, new hypertension occurred in 6.1% on bupropion plus a nicotine patch, 2.5% on bupropion alone, 1.6% on the patch alone and 3.1% on placebo, mostly in people with signs of earlier hypertension [8]. In immediate-release trials, hypertension was reported by 4% against 2% on placebo [8].
Population
Randomized trials of bupropion alone or with naltrexone [24]; smokers in a four-arm trial and adults in immediate-release trials described in labeling [8].
Sources
[24], [8]
Caveats
The pooled figure mixes bupropion alone with the naltrexone combination, which raised pressure more [24]. In the smoking trial, bupropion alone did not exceed placebo.
LimitedCommon

Heart rhythm

The label reports cardiac arrhythmia in 5% of people on immediate-release bupropion at 300 to 600 mg a day, against 4% on placebo.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In controlled trials of the immediate-release form at 300 to 600 mg a day, cardiac arrhythmia was reported by 5% against 4% on placebo [8]. In a review of misuse cases, a fast heart rate was the most frequent effect at presentation [25].
Population
Adults in immediate-release trials described in labeling [8]; published cases of misuse by snorting or injection [25].
Sources
[8], [25]
Caveats
A one-point difference from placebo in trials that ran up to 600 mg a day, with no type of arrhythmia named.
ModerateCommon

Rash and allergic reactions

Shown to raise rash, in 4% to 5% against 1% on placebo in depression trials. Severe allergic reactions were reported during trials and after approval.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In depression trials, rash occurred in 5% at 300 mg a day and 4% at 400 mg a day against 1% on placebo, and hives in 2% and 1% against 0% [15]. The label states that anaphylactoid reactions with itching, hives, swelling and shortness of breath occurred during clinical trials, and that Stevens-Johnson syndrome and anaphylactic shock have been reported rarely after approval [8].
Population
490 adults on sustained-release bupropion and 385 on placebo [15]; trial and postmarketing reports [8].
Sources
[15], [8]
Caveats
The label gives no rate for the severe reactions.
ModerateUncommon

Seizures

The label warns bupropion can cause dose-related seizures, about 1 in 1,000 at up to 300 mg a day and 4 in 1,000 at 300 to 450 mg.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
In studies of the sustained-release form at up to 300 mg a day, seizures occurred in about 0.1% of patients. In a prospective follow-up study of the immediate-release form at 300 to 450 mg a day, the incidence was about 0.4% (13 of 3,200). The label states the estimated incidence rises almost tenfold between 450 and 600 mg a day. It lists a seizure disorder, anorexia or bulimia, and abrupt stopping of alcohol, benzodiazepines, barbiturates or antiepileptic drugs as contraindications, and names antipsychotics, other antidepressants, theophylline and systemic corticosteroids as drugs that lower the seizure threshold [8].
Population
Patients in sustained-release studies and 3,200 people in an immediate-release follow-up study [8].
Sources
[8]
Caveats
No placebo rates are given. The incidence with the extended-release form has not been formally measured in trials [8].
LimitedHow often is not known

Mania, psychosis and confusion

The label reports delusions, hallucinations, psychosis, paranoia and confusion in people treated for depression, and warns of triggering mania. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that depressed patients treated with bupropion have had delusions, hallucinations, psychosis, concentration disturbance, paranoia and confusion, some of them with a diagnosis of bipolar disorder, and that symptoms eased in some cases when the dose was lowered or the drug withdrawn. It also states that antidepressant treatment can precipitate a manic or hypomanic episode [8]. In immediate-release trials, confusion was reported by 8% against 5% on placebo and hostility by 6% against 4% [8].
Population
Reports and immediate-release trials summarized in labeling [8].
Sources
[8]
Caveats
The label gives no rate for psychosis or mania.
LimitedHow often is not known

Use with MAOIs

The label lists MAOIs as a contraindication, within 14 days in either direction, because of an increased risk of hypertensive reactions.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that bupropion blocks the reuptake of dopamine and norepinephrine and that use with a monoamine oxidase inhibitor is contraindicated because of an increased risk of hypertensive reactions. It applies the same to the antibiotic linezolid and intravenous methylene blue. It cites animal studies in which the MAOI phenelzine increased bupropion's acute toxicity [8].
Population
Labeling statement [8].
Sources
[8]
Caveats
The label gives no rate in people.
LimitedHow often is not known

Raised levels of other drugs

The label states bupropion slows a liver enzyme and can raise levels of many antidepressants, antipsychotics, beta blockers and heart rhythm drugs.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that bupropion and its metabolites inhibit the enzyme CYP2D6 and can raise exposure to drugs it clears. Its examples are the antidepressants venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine and sertraline, the antipsychotics haloperidol, risperidone and thioridazine, the beta blocker metoprolol and the heart rhythm drugs propafenone and flecainide. It states that tamoxifen, which needs this enzyme to become active, could in theory have a reduced effect. In the other direction, ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital and phenytoin can lower bupropion levels, and ticlopidine and clopidogrel can raise them [8].
Population
Labeling statements drawn from drug interaction studies [8].
Sources
[8]
Caveats
These are changes in drug levels, not rates of harm. The tamoxifen statement is theoretical.
LimitedHow often is not known

Alcohol

The label reports rare postmarketing cases of neuropsychiatric events or lower alcohol tolerance in people drinking while on bupropion. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label describes rare postmarketing reports of adverse neuropsychiatric events or reduced alcohol tolerance in people who drank alcohol during treatment. It lists abrupt stopping of alcohol as a contraindication and excessive alcohol use as a condition that raises seizure risk [8].
Population
Postmarketing reports summarized in labeling [8].
Sources
[8]
Caveats
Voluntary reports from a population of unknown size.
LimitedHow often is not known

Levodopa and amantadine

The label reports nervous system toxicity, including restlessness, tremor and unsteady walking, when bupropion was taken with levodopa or amantadine.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that central nervous system toxicity has been reported when bupropion was given with levodopa or amantadine, with restlessness, agitation, tremor, ataxia, gait disturbance, vertigo and dizziness. It presumes the cause is the combined dopamine effect of the drugs [8].
Population
Reports summarized in labeling [8].
Sources
[8]
Caveats
No denominator.
LimitedHow often is not known

Misuse

Case reports: snorting or injecting bupropion has been described almost only in people with a substance use history. A review called misuse uncommon.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
A systematic review of misuse cases found that insufflation and intravenous injection occurred almost exclusively in people with a history of substance use disorder. The most frequent effect at presentation was a fast heart rate, followed by seizures, and injection caused skin infection and tissue damage [25]. A second review concluded that misuse occurs in practice and is uncommon, and that bupropion lacks some reinforcing effects of other stimulants [27]. The label reports mild amphetamine-like activity after a single 400 mg dose in people experienced with drugs of abuse [8].
Population
Published cases of bupropion misuse [25]; preclinical, clinical and postmarketing studies [27].
Sources
[25], [27], [8]
Caveats
No denominator, so no rate. Bupropion is not a controlled substance [8].
LimitedHow often is not known

Falls in older adults

One trial found the rate of falls was highest when bupropion was added to an existing antidepressant in adults aged 60 and older.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Among older adults with treatment-resistant depression assigned to added aripiprazole, added bupropion or a switch to bupropion, the rate of falls was highest with added bupropion [11].
Population
619 adults aged 60 and older, 206 of them assigned to added bupropion [11].
Sources
[11]
Caveats
One trial with no placebo arm. The abstract gives no fall rates.
LimitedHow often is not known

Angle-closure glaucoma

The label warns that pupil widening on antidepressants can trigger an angle-closure attack in people with untreated narrow angles. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that the pupillary dilation that follows use of many antidepressants, including bupropion, may trigger an angle-closure attack in a person with anatomically narrow angles who has not had an iridectomy [8].
Population
Labeling statement [8].
Sources
[8]
Caveats
No rate and no trial data are given.
LimitedHow often is not known

False-positive urine drug tests

The label reports false-positive urine screening tests for amphetamines in people taking bupropion, which confirmatory testing can tell apart.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that false-positive urine immunoassay screens for amphetamines have been reported, including after bupropion is stopped, because some screening tests lack specificity. Gas chromatography with mass spectrometry distinguishes bupropion from amphetamines [8].
Population
Reports summarized in labeling [8].
Sources
[8]
Caveats
No rate is given.
LimitedHow often is not known

Symptoms after stopping

Case reports: anxiety, irritability, poor sleep, aches and, in one patient, acute dystonia followed stopping bupropion. No study giving a rate was located.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
A 32-year-old man treated for nicotine dependence had irritable mood, anxiety, sleeplessness, headache and generalized aches after stopping bupropion abruptly [28]. A patient with major depression had acute dystonia, with trouble swallowing, jaw clenching and a twisted neck, twice after abrupt stops, once when switched to duloxetine and once after two missed doses, and it resolved with bupropion restarted or biperiden [29]. A 36-year-old woman had body aches, drowsiness, dizziness, anxiety and agitation 2 days after stopping 150 mg a day of the extended-release form, with no other cause found on blood tests and a viral panel. Symptoms stopped within 2 days of restarting it [30].
Population
Single case reports [28][29][30].
Sources
[28], [29], [30]
Caveats
Case reports cannot give a rate or prove cause. The 2024 report describes such reports as rare and notes that bupropion's half-life of 12 to 30 hours may delay symptoms by several days [30].

Mixed results1

LimitedCommon

Mood and behavior changes while quitting smoking

One trial found no significant rise in moderate or severe neuropsychiatric events on bupropion, 2.2% against 2.4% on placebo in smokers without psychiatric illness.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In smokers without a psychiatric disorder, moderate and severe neuropsychiatric adverse events occurred in 2.2% on bupropion and 2.4% on placebo (risk difference -0.08, 95% CI -1.37 to 1.21). In smokers with a psychiatric disorder, they occurred in 6.7% and 4.9% (risk difference 1.78, 95% CI -0.24 to 3.81) [6]. The label reports postmarketing cases in people taking bupropion to quit smoking, including depression, mania, psychosis, hallucinations, aggression, suicidal thoughts and suicide. It notes that depressed mood can also be a symptom of nicotine withdrawal [8].
Population
8,144 smokers, 4,116 with and 4,028 without a psychiatric disorder [6].
Sources
[6], [8]
Caveats
One trial, though a large one. The postmarketing reports have no denominator. In the psychiatric group, the interval for the difference from placebo reached up to 3.8 percentage points.
Why limited
This rests on one trial, of 8,144 people. Strength counts independent studies that agree, so one trial is limited at any size.

Checked, no increase found2

Strong

Sexual side effects

Not shown to raise sexual side effects above placebo in two meta-analyses, unlike SSRIs in the same trials.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
A meta-analysis of treatment-emergent sexual dysfunction found no significant difference between bupropion and placebo [23]. In seven trials, SSRIs produced more sexual side effects than bupropion or placebo, and bupropion produced no more than placebo [1]. In trials of the immediate-release form, decreased libido was reported by 3% against 2% on placebo [8].
Population
Antidepressant studies pooled by drug [23]; adults in 7 randomized trials of bupropion, SSRIs and placebo [1]; adults in immediate-release trials at 300 to 600 mg a day [8].
Sources
[23], [1], [8]
Caveats
The band above is the label rate for decreased libido, which sat close to placebo. Neither meta-analysis abstract gives the bupropion rate.
ModerateStudied in pregnancy

Pregnancy

Not linked to more birth defects overall. The pregnancy registry rate of heart defects was 1.3%, close to the background rate of about 1%.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
A meta-analysis of four studies put the pooled share of congenital malformations among live-born infants exposed to bupropion at 1.0% (95% CI 0.0 to 3.0), with mean birth weight of 3,306 g and mean gestation of 39.2 weeks [26]. The label reports no increase in malformations overall in a registry of 675 first-trimester exposures and a database study of 1,213. Cardiovascular malformations occurred in 1.3% of registry pregnancies, against a background rate of about 1% [8].
Population
18 studies, including 2 RCTs and 11 cohorts, of bupropion or varenicline in pregnancy [26]; 675 and 1,213 first-trimester exposures [8].
Sources
[26], [8]
Caveats
The review rated the available evidence poor in quality, with high heterogeneity (I² 81%), and found no strong evidence of either harm or absence of harm [26]. The label notes the registry suggested a possible increase in heart defects that later studies did not confirm overall [8].

Claims tested and not found

  1. That bupropion raises quit rates as much as varenicline. Quit rates were lower on bupropion than on varenicline in 9 studies (RR 0.73, 95% CI 0.67 to 0.80) [4], and in a head-to-head trial abstinence was more likely on varenicline (OR 1.75, 95% CI 1.52 to 2.01) [6].
  2. That adding bupropion to nicotine replacement raises quit rates over nicotine replacement alone. Across 15 studies the difference was not statistically clear (RR 1.17, 95% CI 0.95 to 1.44, low-certainty evidence) [4].
  3. That bupropion causes drowsiness. Somnolence was less frequent on bupropion than on placebo in a meta-analysis of depression trials [21], and occurred in 2% to 3% against 2% on placebo in label trials [15].
  4. That a low once-daily dose relieves antidepressant-related sexual problems. In two studies of 150 mg once daily, response did not differ from placebo (RR 0.62, 95% CI 0.09 to 4.41) [17].

Related

Naltrexone-bupropion

Sources

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