Wellbutrin (buproprion) Side Effects, Warnings, and Drug Interactions

Medically Reviewed on 11/9/2022

What Is Wellbutrin (bupropion)?

Wellbutrin (bupropion, Zyban, Aplenzin, Fortivo XL) is an aminoketone antidepressant used to manage major depression (major depressive disorder) and seasonal affective disorder.

Wellbutrin is also prescribed for smoking cessation.

Off-label uses for bupropion include:

Common side effects of Wellbutrin include:

Serious side effects of Wellbutrin include high blood pressure (hypertension) and unusual thoughts or behaviors (hallucinations, paranoia, feeling confused).

Drugs that may cause harmful interactions with Wellbutrin include:

There are no adequate studies of Wellbutrin in pregnant women. In one study, there was no difference between Wellbutrin and other antidepressants in the occurrence of birth defects. Wellbutrin should only be used in pregnancy if the benefit outweighs the potential risk. Wellbutrin is secreted in breast milk.

What are the side effects of Wellbutrin (bupropion)?


Four of every 1,000 persons who receive bupropion in doses less than 450 mg/day experience seizures. When doses exceed 450 mg/day, the risk increases tenfold. Other risk factors for seizures include past injury to the head and medications that can lower the threshold for seizures. (See drug interactions.)

Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of bupropion or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be closely observed for clinical worsening, suicidality, or unusual changes in behavior.

The most common side effects associated with bupropion include:

In some people, agitation or insomnia is most marked shortly after starting therapy.

Less common side effects include:

More serious side effects include:

Wellbutrin (bupropion) side effects list for healthcare professionals

The following adverse reactions are discussed in greater detail in other sections of the labeling:

Clinical trials experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse reactions leading to discontinuation of treatment

Adverse reactions were sufficiently troublesome to cause discontinuation of treatment with Wellbutrin in approximately 10% of the 2,400 subjects and healthy volunteers who participated in clinical trials during the product's initial development. The more common events causing discontinuation include neuropsychiatric disturbances (3.0%), primarily agitation and abnormalities in mental status; gastrointestinal disturbances (2.1%), primarily nausea and vomiting; neurological disturbances (1.7%), primarily seizures, headaches, and sleep disturbances; and dermatological problems (1.4%), primarily rashes. It is important to note, however, that many of these events occurred at doses that exceed the recommended daily dose.

Commonly observed adverse reactions

Adverse reactions commonly encountered in subjects treated with Wellbutrin are agitation, dry mouth, insomnia, headache/migraine, nausea/vomiting, constipation, tremor, dizziness, excessive sweating, blurred vision, tachycardia, confusion, rash, hostility, cardiac arrhythmia, auditory disturbance.

Table 2 summarizes the adverse reactions that occurred in placebo-controlled trials at an incidence of at least 1% of subjects receiving Wellbutrin and more frequently in these subjects than in the placebo group.

Table 2: Adverse Reactions Reported by at Least 1% of Subjects and at a Greater Frequency than Placebo in Controlled Clinical Trials

Adverse Reaction Wellbutrin
(n = 323) %
(n = 185) %
Cardiac arrhythmias 5.3 4.3
Dizziness 22.3 16.2
Hypertension 4.3 1.6
Hypotension 2.5 2.2
Palpitations 3.7 2.2
Syncope 1.2 0.5
Tachycardia 10.8 8.6
Pruritus 2.2 0.0
Rash 8.0 6.5
Appetite increase 3.7 2.2
Constipation 26.0 17.3
Dyspepsia 3.1 2.2
Nausea/vomiting 22.9 18.9
Impotence 3.4 3.1
Menstrual complaints 4.7 1.1
Urinary frequency 2.5 2.2
Arthritis 3.1 2.7
Akathisia 1.5 1.1
Cutaneous temperature 1.9 1.6
Dry mouth 27.6 18.4
Excessive sweating 22.3 14.6
Headache/migraine 25.7 22.2
Impaired sleep quality 4.0 1.6
Insomnia 18.6 15.7
Sedation 19.8 19.5
Sensory disturbance 4.0 3.2
Tremor 21.1 7.6
Agitation 31.9 22.2
Anxiety 3.1 1.1
Confusion 8.4 4.9
Decreased libido 3.1 1.6
Delusions 1.2 1.1
Euphoria 1.2 0.5
Hostility 5.6 3.8
Fever/chills 1.2 0.5
Special Senses
Auditory disturbance 5.3 3.2
Blurred vision 14.6 10.3
Gustatory disturbance 3.1 1.1

Other adverse reactions observed during the clinical development of Wellbutrin

The conditions and duration of exposure to Wellbutrin varied greatly, and a substantial proportion of the experience was gained in open and uncontrolled clinical settings. During this experience, numerous adverse events were reported; however, without appropriate controls, it is impossible to determine with certainty which events were or were not caused by Wellbutrin. The following enumeration is organized by organ system and describes events in terms of their relative frequency of reporting in the database.

The following definitions of frequency are used: Frequent adverse reactions are defined as those occurring in at least 1/100 subjects. Infrequent adverse reactions are those occurring in 1/100 to 1/1,000 subjects, while rare events are those occurring in less than 1/1,000 subjects.

Altered Appetite And Weight

A weight loss of greater than 5 lbs. occurred in 28% of subjects receiving Wellbutrin. This incidence is approximately double that seen in comparable subjects treated with tricyclics or placebo. Furthermore, while 35% of subjects receiving tricyclic antidepressants gained weight, only 9.4% of subjects treated with Wellbutrin did. Consequently, if weight loss is a major presenting sign of a patient's depressive illness, the anorectic and/or weight-reducing potential of Wellbutrin should be considered.

Post-marketing experience

The following adverse reactions have been identified during post-approval use of Wellbutrin and are not described elsewhere on the label. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body (general)

Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity. These symptoms may resemble serum sickness.


Hypertension (in some cases severe), orthostatic hypotension, third-degree heart block.


Hyponatremia, syndrome of inappropriate anti-diuretic hormone secretion, hyperglycemia, hypoglycemia.


Esophagitis, hepatitis.

Hemic and lymphatic

Ecchymosis, leukocytosis, leukopenia, thrombocytopenia. Altered PT and/or INR, infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was co-administered with warfarin.


Muscle rigidity/fever/rhabdomyolysis, muscle weakness.

Nervous system

Aggression, coma, completed suicide, delirium, dream abnormalities, paranoid ideation, paresthesia, parkinsonism, restlessness, suicide attempt, unmasking of tardive dyskinesia.

Skin and appendages

Stevens-Johnson syndrome, angioedema, exfoliative dermatitis, urticaria.

Special senses

Tinnitus, increased intraocular pressure.

What drugs interact with Wellbutrin (bupropion)?

Potential for other drugs to affect Wellbutrin

Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between Wellbutrin 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 Wellbutrin may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel).

Inducers of CYP2B6

Ritonavir, Lopinavir, and Efavirenz

Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of Wellbutrin may be necessary when coadministered with ritonavir, lopinavir, or efavirenz 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. 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.

Potential for Wellbutrin to affect other drugs

Drugs metabolized by CYP2D6

Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, co-administration of Wellbutrin 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 Wellbutrin, 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 Wellbutrin and such drugs may require increased doses of the drug.


Coadministration of Wellbutrin with digoxin may decrease plasma digoxin levels. Monitor plasma digoxin levels in patients treated concomitantly with Wellbutrin and digoxin.

Drugs that lower seizure threshold

Use extreme caution when co-administering Wellbutrin 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.

Dopaminergic drugs (levodopa and amantadine)

Bupropion, levodopa, and amantadine have dopamine agonist effects. CNS toxicity has been reported when bupropion was co-administered 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 Wellbutrin concomitantly with these drugs.

Use with alcohol

In post-marketing experience, there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with Wellbutrin. The consumption of alcohol during treatment with Wellbutrin should be minimized or avoided.

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 Wellbutrin. Conversely, at least 14 days should be allowed after stopping Wellbutrin before starting an MAOI antidepressant.

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 the discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.

Does Wellbutrin (bupropion) cause addiction or withdrawal symptoms?

Controlled substance

Bupropion is not a controlled substance.



Controlled clinical trials conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed subjects showed some increase in motor activity and agitation/excitement, often typical of central stimulant activity.

In a population of individuals experienced with drugs of abuse, a single oral dose of 400 mg of bupropion produced mild amphetamine-like activity as compared with placebo on the Morphine-Benzedrine Subscale of the Addiction Research Center Inventories (ARCI) and a score greater than placebo but less than 15 mg of the Schedule II stimulant dextroamphetamine on the Liking Scale of the ARCI. These scales measure general feelings of euphoria and drug liking which are often associated with abuse potential.

Findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs. Nonetheless, evidence from single-dose trials does suggest that the recommended daily dosage of bupropion when administered orally in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers. However, higher doses (which could not be tested because of the risk of seizure) might be modestly attractive to those who abuse CNS stimulant drugs.

Wellbutrin is intended for oral use only. The inhalation of crushed tablets or injection of dissolved bupropion has been reported. Seizures and/or cases of death have been reported when bupropion has been administered intranasally or by parenteral injection.


Studies in rodents and primates demonstrated that bupropion exhibits some pharmacologic actions common to psychostimulants. In rodents, it has been shown to increase locomotor activity, elicit a mild stereotyped behavior response, and increase rates of responding in several schedule-controlled behavior paradigms. In primate models assessing the positive-reinforcing effects of psychoactive drugs, bupropion was self-administered intravenously. In rats, bupropion produced amphetamine-like and cocaine-like discriminative stimulus effects in drug discrimination paradigms used to characterize the subjective effects of psychoactive drugs.


Common side effects of the antidepressant Wellbutrin (bupropion, Zyban, Aplenzin, Fortivo XL) include weight loss, skin rash, sweating, ringing in the ears (tinnitus), shakiness, stomach pain, dizziness, muscle pain, fast heartbeat, sore throat, frequent urination, agitation, dry mouth, insomnia, headache, nausea, constipation, and tremor.

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Medically Reviewed on 11/9/2022
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Professional side effects, drug interactions, and addiction sections courtesy of the U.S. Food and Drug Administration