Bupropion

Pharmacologic Category

Antidepressant, Dopamine/Norepinephrine-Reuptake Inhibitor; Smoking Cessation Aid

Dosing: Adult

Note: Bupropion is available as hydrochloride and hydrobromide salts. Doses are expressed in this monograph as hydrochloride salt except where noted as bupropion hydrobromide salt. Bupropion hydrochloride 150 mg is equivalent to about 174 mg of bupropion hydrobromide. Bupropion is available as immediate release, 12-hour extended release (sustained release), and 24-hour extended release tablets.

Attention-deficit/hyperactivity disorder (off-label use): Note: For patients with comorbid mood disorders or as an alternative agent for patients with substance use disorders (Brent 2019; CANMAT [Bond 2012]).

12-hour extended release (sustained release): Oral: Initial: 100 mg once daily in the morning; increase in 100 mg/day increments at intervals of 3 to 4 weeks based on response and tolerability up to 200 mg twice daily (Bukstein 2019; Reimherr 2005; Wilens 2001).

24-hour extended release: Oral: Initial: 150 mg once daily in the morning for 1 week; increase to 300 mg once daily for 3 weeks; may further increase dose based on response and tolerability up to 450 mg once daily (Wilens 2005).

Bipolar depression (off-label use): 12-hour extended release (sustained release): Oral: Initial: 100 mg once daily as an adjunct to mood stabilizer; increase based on response and tolerability at 2-week intervals up to 450 mg/day in 2 divided doses (average dose in clinical trials was 250 mg/day) (APA 2002; Grossman 1999; McIntyre 2002).

Major depressive disorder (unipolar): Note: Treatment should be periodically evaluated at appropriate intervals to ensure lowest effective dose is used. Slower dose titrations may be indicated based on patient care setting, symptom severity, and concern for side effects. May also be used as an alternative agent for patients with SSRI-induced sexual dysfunction (APA 2010).

Immediate release: Oral: Initial: 100 mg twice daily; after 3 days may increase to the usual dose of 100 mg 3 times a day; if no clinical improvement after several weeks, may increase to a maximum dose of 450 mg/day in 3 or 4 divided doses; do not exceed 150 mg in a single dose.

12-hour extended release (sustained release): Oral: Initial: 150 mg daily in the morning; if tolerated, after 3 days, may increase to a target dose of 150 mg twice daily; if no clinical improvement after several weeks, may increase to a maximum dose of 200 mg twice daily; do not exceed 200 mg in a single dose.

24-hour extended release: Oral:

Hydrochloride salt: Initial: 150 mg once daily in the morning; if tolerated, may increase as early as day 4 of dosing to 300 mg once daily; if no clinical improvement after 2 weeks, may increase to 450 mg once daily.

Hydrobromide salt: Initial: 174 mg once daily in the morning; may increase as early as day 4 of dosing to 348 mg once daily (target dose).

Seasonal affective disorder (SAD): 24-hour extended release: Oral:

Hydrochloride salt: Initial: 150 mg once daily in the morning; if tolerated, may increase after 7 days to 300 mg once daily in the morning.

Hydrobromide salt: Initial: 174 mg once daily in the morning; if tolerated, may increase after 7 days to 348 mg once daily in the morning.

Note: Prophylactic treatment should be reserved for patients with frequent depressive episodes and/or significant impairment. Initiate treatment in the autumn prior to symptom onset, and discontinue in early spring with dose tapering. Doses >300 mg daily (hydrochloride salt) or >348 mg daily (hydrobromide salt) have not been studied in SAD.

Selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction, augmentation (off-label use): 12-hour extended release (sustained release): Oral: Initial: 150 mg once daily for the first 3 days; increase to 150 mg twice daily, based on response and tolerability (Clayton 2004; Safarinejad 2011).

Smoking cessation: Note: May be used as monotherapy or in combination with nicotine replacement therapy (Siu 2015): 12-hour extended release (sustained release): Oral: Initial: 150 mg once daily for 3 days; increase to 150 mg twice daily (maximum dose: 300 mg/day). For patients who do not tolerate titration to the full dose, consider continuing 150 mg once daily; the lower dose has shown efficacy (Hughes 2014).

Note: Therapy should begin at least 1 week before target quit date. Target quit dates are generally in the second week of treatment. If patient successfully quits smoking after 7 to 12 weeks but is not ready to discontinue treatment, may consider ongoing maintenance therapy based on individual patient risk:benefit. Efficacy of maintenance therapy (300 mg daily) has been demonstrated for up to 1 year. Conversely, if significant progress has not been made by the seventh week of therapy, success is unlikely; consider combination therapy, or discontinuation and use of an alternative agent.

Dosing conversion:

Immediate-, 12-hour (sustained release), and 24-hour extended-release formulations (hydrochloride salt): Convert using same total daily dose (up to the maximum recommended dose for a given dosage form), but adjust frequency as indicated for immediate (3 to 4 times daily), 12-hour extended (sustained release) (twice daily), or 24-hour extended (once daily) release products.

Hydrochloride salt formulation (immediate release, 12-hour (sustained release), or 24-hour extended release) to hydrobromide salt formulation (extended release):

Bupropion hydrochloride 150 mg daily is equivalent to bupropion hydrobromide 174 mg once daily.

Bupropion hydrochloride 300 mg daily is equivalent to bupropion hydrobromide 348 mg once daily.

Bupropion hydrochloride 450 mg daily is equivalent to bupropion hydrobromide 522 mg once daily.

MAOI recommendations: Switching to or from an MAOI antidepressant:

Allow 14 days to elapse between discontinuing an MAOI intended to treat depression and initiation of bupropion.

Allow 14 days to elapse between discontinuing bupropion and initiation of an MAOI intended to treat depression.

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose (eg, over 2 to 4 weeks) to allow for the detection of reemerging symptoms. Withdrawal symptoms resulting from abrupt discontinuation are unlikely because bupropion has minimal serotonergic activity (APA 2010).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing; use with caution.

Discontinuation of therapy: Refer to adult dosing.

MAOI recommendations: Refer to adult dosing.

Dosing: Renal Impairment: Adult

Use with caution; manufacturer’s labeling suggests a reduction in dose and/or frequency be considered but does not provide specific dosing recommendations. Use of the 450 mg extended-release tablet is not recommended (Forfivo XL is not available in a lower dose strength).

Dosing: Hepatic Impairment: Adult

Mild impairment (Child-Pugh score 5 to 6): Use with caution; manufacturer's labeling suggests a reduction in dose and/or frequency be considered but does not provide specific dosing recommendations. Some experts recommend decreasing the initial dose to 50% of usual dose and reducing dosing frequency (Mullish 2014). Use of the 450 mg ER tablet is not recommended (Forfivo XL is not available in a lower dose strength).

Moderate to severe impairment, including severe hepatic cirrhosis (Child-Pugh score 7 to 15): Use with extreme caution. Some experts recommend decreasing the initial dose to 50% of usual dose and reducing dosing frequency (Mullish 2014).

Hydrobromide salt: Maximum dose: 174 mg every other day.

Hydrochloride salt:

Immediate release: Maximum dose: 75 mg once daily.

12-hour extended release (sustained release): Maximum dose: 100 mg once daily or 150 mg every other day.

24-hour extended release: Maximum dose: 150 mg every other day.

Dosing: Pediatric

Note: Bupropion is available as either hydrochloride or hydrobromide (Aplenzin; not used in pediatric patients) salt formulations which are not interchangeable on a mg per mg basis; dosage expressed in terms of the salt formulation. Bupropion is available as immediate-release, 12-hour sustained-release, and 24-hour extended-release tablets. Patients must be able to swallow sustained or extended-release products whole.

Attention-deficit/hyperactivity disorder: Limited data available: Children ≥6 years (Dopheide 2009; Pliszka 2007) and Adolescents: Oral:

Immediate release, hydrochloride salts: Initial: 3 mg/kg/day in 2 to 3 divided doses; maximum initial dose: 150 mg/day; titrate dose as needed to a maximum daily dose of 6 mg/kg/day or 300 mg/day with no single dose >150 mg (Dopheide 2009; Pliszka 2007).

12-hour sustained release (Wellbutrin SR) and 24-hour extended release (Wellbutrin XL), hydrochloride salts: May be used in place of regular tablets, once the daily dose is titrated using the immediate release product and the titrated 12-hour dosage corresponds to a sustained release tablet (Wellbutrin SR) or the 24-hour dosage range corresponds to an extended release tablet size (Wellbutrin XL)

Depression, refractory to SSRIs: Limited data available; Note: May be most beneficial in patients with comorbid ADHD, conduct disorder, substance abuse problems or who want to quit smoking (Dopheide 2006). Treatment should be periodically evaluated at appropriate intervals to ensure lowest effective dose is used.

Immediate release, hydrochloride salt: Children 8 to ≤11 years: Oral: Initial: 37.5 mg twice daily; titrate to response; usual dosage range: 100 to 400 mg/day (Dopheide 2006)

12-hour sustained release, hydrochloride salt (Wellbutrin SR): Children ≥11 years and Adolescents: Oral: Initial: 2 mg/kg up to 100 mg administered as a morning dose; may titrate as needed every 2 to 3 weeks using the following titration schedule: Step 2: Increase up to 3 mg/kg every morning; Step 3: Increase up to 3 mg/kg every morning and 2 mg/kg at 5 pm (17:00); Step 4: Increase up to 3 mg/kg/dose twice daily; maximum dose: 150 mg; reported mean effective dose: Morning: 2.2 mg/kg and afternoon: 1.7 mg/kg (Daviss 2001)

24-hour extended release, hydrochloride salt (Wellbutrin XL): Children ≥12 years and Adolescents: Oral: Initial: 150 mg once daily; may titrate after 2 weeks to 300 mg once daily if adequate response not achieved; dosing based on a pharmacokinetic study in eight patients with depression (Daviss 2006); doses as high as 400 mg/day have been reported (Dopheide 2006); may also be used once the daily dose is titrated using the immediate release product and the 24-hour dosage range corresponds to an extended release tablet size (Wellbutrin XL).

Smoking cessation: Limited data available: Adolescents ≥14 years and ≥40.5 kg: 12-hour sustained release, hydrochloride salt (Buproban, Zyban): Oral: Initial: 150 mg once daily for 3 days; increase to 150 mg twice daily; treatment should start while the patient is still smoking in order to allow drug to reach steady-state levels prior to smoking cessation; generally, patients should stop smoking during the second week of treatment; maximum daily dose: 300 mg/day; short-term efficacy was demonstrated in 104 adolescents who received therapy for 7 weeks with cessation counseling (Muramoto 2007).

Dosing conversion between hydrochloride salt immediate (Wellbutrin), 12-hour sustained (Wellbutrin SR), and 24-hour extended-release (Wellbutrin XL) products: Convert using same total daily dose (up to the maximum recommended dose for a given dosage form), but adjust frequency as indicated for 12-hour sustained (twice daily) or for 24-hour extended (once daily) release products.

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to allow for the detection of reemerging symptoms. Withdrawal symptoms resulting from abrupt discontinuation are unlikely because bupropion has minimal serotonergic activity (APA 2010).

MAO inhibitor recommendations: Switching to or from an MAO inhibitor antidepressant:

Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat depression and initiation of bupropion.

Allow 14 days to elapse between discontinuing bupropion and initiation of an MAO inhibitor intended to treat depression.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested; use with caution.

Dosing: Hepatic Impairment: Pediatric

There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested.

Use: Labeled Indications

Major depressive disorder (unipolar [excluding Zyban]): Treatment of major depressive disorder (MDD)

Seasonal affective disorder (24-hour extended release [Aplenzin, Wellbutrin XL]): Prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD)

Smoking cessation (12-hour extended release [sustained release; Zyban]): As an aid to smoking cessation treatment

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

​Attention-deficit/hyperactivity disorderLevel of Evidence [B, G]

Data from a meta-analysis support the use of bupropion in the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults Ref.

Based on the Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force recommendations for the management of mood disorders and comorbid ADHD, bupropion is first-line treatment in patients with ADHD and comorbid bipolar disorder when used as an adjunct to mood stabilizers. Additionally, these guidelines recommend bupropion as a first-line option in patients with ADHD and comorbid major depressive disorder Ref. Access Full Off-Label Monograph

​Bipolar depressionLevel of Evidence [B, G]

Data from a meta-analysis support the use of bupropion in the treatment of bipolar depression. Despite demonstrating the efficacy of bupropion, the authors of this meta-analysis caution that there is a risk of switching from depression to mania when bupropion is used for this indication Ref.

Based on the 2002 American Psychiatric Association (APA) guideline for the treatment of patients with bipolar disorder and the 2018 CANMAT and International Society for Bipolar Disorders guidelines for the management of patients with bipolar disorder, augmentation with bupropion is second-line for the management of bipolar depression that does not respond to preferred treatments. Due to inconsistencies in bupropion augmentation clinical trial results, the World Federation of Societies of Biological Psychiatry guidelines recommend bupropion augmentation of lithium or valproic acid as an option only in patients who are unresponsive to treatments with greater evidence.

​Selective serotonin reuptake inhibitor-induced sexual dysfunction, augmentationLevel of Evidence [B, G]

Data from two randomized, double-blind, placebo-controlled trials support the use of bupropion as an augmentation strategy for increasing sexual desire, arousal, lubrication, orgasm, and satisfaction in patients with selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction who have achieved remission on a serotonergic antidepressant Ref.

Based on the APA practice guideline for the treatment of patients with major depressive disorder, bupropion given for SSRI-induced sexual dysfunction is recommended for the management of side effects of arousal, erectile dysfunction, or orgasm dysfunction.

Level of Evidence Definitions

​Level of Evidence Scale

Clinical Practice Guidelines

Attention-Deficit/Hyperactivity Disorder:

Canadian Network for Mood and Anxiety Treatments (CANMAT), “The Canadian Network for Mood and Anxiety Treatments task force recommendations for the management of patients with mood disorders and comorbid attention-deficit/hyperactivity disorder,” 2012.

Bipolar Disorder:

American Psychiatric Association, "Practice Guideline for the Treatment of Patients with Bipolar Disorder (Revision)," 2002

CANMAT/ISBD, "2018 Guidelines for the Management of Patients With Bipolar Disorder," March 2018

WFSBP, “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2010 on the Treatment of Acute Bipolar Depression,” 2010

Cardiovascular Disease Prevention:

American College of Cardiology/American Heart Association (ACC/AHA), “2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease,” March 2019

Chronic Obstructive Pulmonary Disease:

GOLD, "Global Strategy for Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease," 2019

Depression:

American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, May 2010

Canadian Network for Mood and Anxiety Treatments (CANMAT), “Clinical Guidelines for the Management of Major Depressive Disorder in Adults,” October 2009

National Collaborating Centre for Mental Health (NCCMH), “Depression: The NICE Guideline on the Treatment and Management of Depression in Adults (Updated Edition).” 2010.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the Acute and Continuation Treatment of Unipolar Depressive Disorders,” 2013.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance Treatment of Major Depressive Disorder and Treatment of Chronic Depressive Disorders and Subthreshold Depressions,” 2002.

Nicotine Dependence:

Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline, U.S. Department of Health and Human Services. May 2008

Administration: Oral

May be taken without regard to meals. The manufacturer states that tablets should be swallowed whole; do not crush, chew, or divide.

Immediate release: Administer 3 to 4 times daily with at least 6 hours between successive doses; do not exceed 150 mg in a single dose.

12-hour extended release (sustained release): Administer 2 times daily with at least 8 hours between successive doses; do not exceed 200 mg in a single dose.

24-hour extended release: Administer once daily with at least 24 hours between successive doses.

Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Do not cut, crush, or chew. Switch to IR bupropion. Of note, there is one publication that suggests tablet could be cut in half just prior to administration (Cochren 1999).

Administration: Pediatric

Oral: May be taken without regard to meals. Do not crush, chew, or divide sustained or extended release tablets (hydrochloride and hydrobromide salt formulations); swallow whole. The insoluble shell of the extended-release tablet may remain intact during GI transit and is eliminated in the feces.

Immediate release: Administer with at least 6 hours between successive doses.

Sustained release: Typically administer 2 times daily with at least 8 hours between successive doses

Extended release: Administer once daily with at least 24 hours between successive doses

Storage/Stability

Store at 15°C to 30°C (59°F to 86°F). Protect from light and moisture.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat low mood (depression).

• It is used to treat seasonal affective disorder (SAD).

• It is used to help you stop smoking.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Abdominal pain

• Tremors

• Anxiety

• Nightmares

• Nausea

• Vomiting

• Constipation

• Diarrhea

• Passing gas

• Dry mouth

• Trouble sleeping

• Nose irritation

• Throat irritation

• Sweating a lot

• Lack of appetite

• Tablet shell in stool

• Weight gain or loss

• Joint pain

• Muscle pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Depression like thoughts of suicide, anxiety, agitation, irritability, panic attacks, mood changes, behavioral changes, or confusion

• Confusion

• Behavioral changes

• Seizures

• Thoughts of homicide

• Forceful actions

• Anger

• Sensing things that seem real but are not

• Severe headache

• Severe dizziness

• Passing out

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Swelling

• Shortness of breath

• Hearing changes

• Noise or ringing in the ears

• Passing a lot of urine

• Swollen glands

• Trouble moving

• Trouble focusing

• Vision changes

• Eye pain

• Eye irritation

• Eye redness

• Eye swelling

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Medication Safety Issues

​Sound-alike/look-alike issues:

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Aplenzin: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022108s020lbl.pdf#page=28

Forfivo XL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022497s008lbl.pdf#page=33

Wellbutrin: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018644s052lbl.pdf#page=31

Wellbutrin SR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020358s059lbl.pdf#page=34

Wellbutrin XL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021515s036lbl.pdf#page=28

Zyban: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020711s045s046s047lbl.pdf#page=37

Contraindications

Hypersensitivity to bupropion or any component of the formulation; seizure disorder; history of anorexia/bulimia; patients undergoing abrupt discontinuation of ethanol or sedatives, including benzodiazepines, barbiturates, or antiepileptic drugs; use of MAO inhibitors (concurrently or within 14 days of discontinuing either bupropion or the MAO inhibitor); initiation of bupropion in a patient receiving linezolid or intravenous methylene blue

24-hour extended release: Additional contraindications: Other conditions that increase seizure risk, including arteriovenous malformation, severe head injury, severe stroke, CNS tumor, CNS infection

Canadian labeling: Additional contraindications (not in US labeling): Concurrent use or use within 14 days of thioridazine; concurrent use with other dosage forms of bupropion

Warnings/Precautions

Major psychiatric warnings (use in treating psychiatric disorders):

• Suicidal thinking/behavior (use in treating psychiatric disorders): [US Boxed Warning]: 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 aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and for emergence of suicidal thoughts and behaviors, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); advise families and caregivers of the need for close observation and communication with the prescriber. A medication guide concerning the use of antidepressants should be dispensed with each prescription.

• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their health care provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• CNS stimulation: May cause CNS stimulation (restlessness, anxiety, insomnia) or anorexia.

• Cognitive impairment: May cause motor or cognitive impairment in some patients, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Hypersensitivity reactions: Anaphylactoid/anaphylactic reactions have occurred, with symptoms of pruritus, urticaria, angioedema, and dyspnea. Serious reactions have been (rarely) reported, including erythema multiforme, Stevens-Johnson syndrome and anaphylactic shock. Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity resembling serum sickness have been reported.

• Hypertension: May elevate blood pressure and cause hypertension. Events have been observed in patients with or without evidence of preexisting hypertension. The risk is increased when used concomitantly with monoamine oxidase inhibitors, nicotine replacement, or other drugs that increase dopaminergic or noradrenergic activity. Assess blood pressure before treatment and monitor periodically.

• Mania/hypomania: May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Combination therapy with an antidepressant and a mood stabilizer may be effective for acute treatment of bipolar major depressive episodes but should be avoided in acute mania or mixed episodes as well as maintenance treatment in bipolar disorder due to the mood-destabilizing effects of antidepressants (CANMAT [Yatham 2018]; WFSBP [Grunze 2018]). Patients presenting with depressive symptoms should be screened for bipolar disorder. Bupropion is not FDA-approved for the treatment of bipolar depression.

• Neuropsychiatric effect (use in smoking cessation): Serious neuropsychiatric events have occurred in patients taking bupropion for smoking cessation, including changes in mood (eg, depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, panic, suicidal ideation, suicide attempt, and completed suicide. The majority occurred during bupropion treatment; some occurred during treatment discontinuation. A causal relationship is uncertain as depressed mood may be a symptom of nicotine withdrawal. Some cases also occurred in patients taking bupropion who continued to smoke. Neuropsychiatric effects occurred in patients with and without preexisting psychiatric disease; some patients experienced a worsening of their psychiatric illnesses. However, subsequent controlled trials in patients with or without psychiatric disorders have not identified significant differences in neuropsychiatric effects for patients taking bupropion, varenicline, nicotine patches, or placebo (Anthenelli 2016; Cinciripini 2013). Observe all patients taking bupropion for neuropsychiatric reactions. Instruct patients to stop taking bupropion and contact a health care provider if neuropsychiatric reactions occur.

• Ocular effects: May cause mild pupillary dilation, which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.

• Psychosis: May cause delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion; most common in patients with an underlying psychiatric illness. Symptoms may abate with dose reduction and/or withdrawal of treatment.

• Seizures: May cause a dose-related risk of seizures. Use is contraindicated in patients with a history of seizures or certain conditions with high seizure risk (eg, history of anorexia/bulimia or patients undergoing abrupt discontinuation of ethanol, benzodiazepines, barbiturates, or antiepileptic drugs); 24-hour ER formulations are also contraindicated in patients with certain conditions with high seizure risk (eg, arteriovenous malformation, severe head injury, severe stroke, CNS tumor, and CNS infection). Use caution with concurrent use of antipsychotics, antidepressants, theophylline, systemic corticosteroids, stimulants (including cocaine), anorexiants, or hypoglycemic agents, or with excessive use of ethanol, benzodiazepines, sedative/hypnotics, or opioids. Use with caution in seizure-potentiating metabolic disorders (hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia). The dose-dependent risk of seizures may be reduced by gradual dose increases and by not exceeding the maximum daily dose. Do not coadminister with other bupropion-containing formulations. Permanently discontinue if seizure occurs during therapy. Chewing, crushing, injecting, or dividing long-acting products may increase seizure risk.

• Sexual dysfunction: The incidence of sexual dysfunction with bupropion is generally lower than with selective serotonin reuptake inhibitors (Clayton 2004).

• Weight loss: May cause weight loss; use caution in patients where weight loss is not desirable.

Disease-related concerns:

• Attention-deficit/hyperactivity disorder (off-label use): All children diagnosed with attention-deficit/hyperactivity disorder who may be candidates for stimulant medications should have a thorough cardiovascular assessment to identify risk factors for sudden cardiac death prior to initiation of drug therapy.

• Cardiovascular disease: Use with caution in patients with cardiovascular disease, history of hypertension, or coronary artery disease; treatment-emergent hypertension (including some severe cases) has been reported, both with bupropion alone and in combination with nicotine transdermal systems.

• Hepatic impairment: Use caution in patients with hepatic impairment and use extreme caution in patients with severe hepatic cirrhosis; plasma concentrations are increased. Use caution in patients with hepatic encephalopathy due to the risk of neurocognitive effects (Mauri 2014; Mullish 2014). Consider a reduction in dose and/or frequency.

• Renal impairment: Use with caution in patients with renal impairment; consider a reduction in dose and/or frequency.

Special populations:

• Elderly: Use with caution in elderly patients; may be at greater risk of drug accumulation during chronic dosing. Consider a reduction in dose.

Dosage form specific issues:

• 24-hour ER tablet: Insoluble tablet shell may remain intact and be visible in the stool.

Other warnings/precautions:

• Abuse/misuse: Using doses higher than prescribed may result in increased motor activity, agitation/excitement and euphoria. Inhalation of crushed tablets or injection of dissolved bupropion has been reported, some resulting in seizures and death.

• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy (ECT); consider discontinuing, when possible, prior to ECT treatment (APA 2010).

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Studies have found bupropion effective as an antidepressant for older persons with major depressive disorder and as effective as paroxetine and imipramine. Its side effect profile (minimal anticholinergic and blood pressure effects) is favorable and makes it an alternative to other first-line antidepressants. A single- and multiple-dose pharmacokinetic study suggested that accumulation of bupropion and its metabolites may occur in the elderly.

A systematic review and meta-analysis of antidepressant placebo-controlled trials in persons with depression and dementia found evidence "suggestive" of efficacy but not of sufficient strength to "confirm" efficacy (Nelson 2011). Antidepressant trials in this patient population are small and underpowered. Older patients with depression being treated with an antidepressant should be closely monitored for response and adverse effects. Treatment should be switched or augmented when response is inadequate with a therapeutic dose. Antidepressants that are not tolerated should be discontinued and an alternative agent should be started.

Warnings: Additional Pediatric Considerations

The American Heart Association recommends that all children diagnosed with ADHD who may be candidates for medication, such as bupropion, should have a thorough cardiovascular assessment prior to initiation of therapy. These recommendations are based upon reports of serious cardiovascular adverse events (including sudden death) in patients (both children and adults) taking usual doses of stimulant medications. Most of these patients were found to have underlying structural heart disease (eg, hypertrophic obstructive cardiomyopathy). This assessment should include a combination of thorough medical history, family history, and physical examination. An ECG is not mandatory but should be considered.

Pregnancy Considerations

Bupropion and its metabolites cross the placenta (Fokina 2016).

An increased risk of congenital malformations has not been observed following maternal use of bupropion during pregnancy; however, data specific to cardiovascular malformations is inconsistent. The long-term effects on development and behavior have not been studied.

Therapy with antidepressants during pregnancy should be individualized (ACOG 2008). Psychotherapy or other nonmedication therapies may be considered for some women; however, antidepressant medication should be considered for pregnant women with moderate to severe major depressive disorder (APA 2010). If treatment for MDD is initiated for the first time during pregnancy, agents other than bupropion are preferred (MacQueen 2016). Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (ACOG 2008; APA 2010; Yonkers 2009).

There is insufficient information related to the use of bupropion to recommend use for smoking cessation during pregnancy (ACOG 721 2017).

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Breast-Feeding Considerations

Bupropion and its active metabolites are present in breast milk.

The manufacturer reports the relative infant dose (RID) of bupropion and its active metabolites to be ~2% of a weight-adjusted maternal dose. In one report, the RID of bupropion ranged from 1.4% to 10.6% of the maternal dose when calculated using actual infant weights and maternal doses ranging from 150 to 300 mg/day (Davis 2009).

In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000); however, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).

Bupropion and its active metabolites can be detected in the serum and urine of breastfeeding infants (Davis 2009; Neuman 2014).

Seizures and sleep disturbances have been reported in breastfeeding infants following bupropion exposure via breast milk (Chaudron 2004; Hale 2010; Neuman 2014). Infants of mothers using psychotropic medications should be monitored daily for changes in sleep, feeding patterns, and behavior (Bauer 2013) as well as infant growth and neurodevelopment (Sachs 2013; Sriraman 2015).

When first initiating an antidepressant in a breastfeeding woman, agents other than bupropion are preferred (Berle 2011); however, maternal use of bupropion is not considered a reason to discontinue breastfeeding (Sriraman 2015). If treatment for smoking cessation is needed postpartum, agents other than bupropion are preferred (Sachs 2013). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Lexicomp Pregnancy & Lactation, In-Depth

• BuPROPion

Briggs' Drugs in Pregnancy & Lactation

• Bupropion

Adverse Reactions

>10%:

Cardiovascular: Tachycardia (≤11%)

Central nervous system: Insomnia (11% to 40%), headache (25% to 34%), agitation (2% to 32%), dizziness (6% to 22%)

Dermatologic: Diaphoresis (5% to 22%)

Endocrine & metabolic: Weight loss (14% to 23%)

Gastrointestinal: Xerostomia (10% to 28%), constipation (8% to 26%), nausea and vomiting (23%), nausea (1% to 18%)

Neuromuscular & skeletal: Tremor (1% to 21%)

Ophthalmic: Blurred vision (3% to 15%)

Respiratory: Nasopharyngitis (13%), pharyngitis (3% to 13%), rhinitis (12%)

1% to 10%:

Cardiovascular: Palpitations (2% to 6%), cardiac arrhythmia (5%), chest pain (≤4%), flushing (≤4%), hypertension (1% to 4%; may be severe), hypotension (3%)

Central nervous system: Lack of concentration (9%), confusion (≤8%), anxiety (3% to 8%), hostility (≤6%), nervousness (4% to 5%), abnormal dreams (3% to 5%), abnormal sensory symptoms (4%), sleep disorder (4%), migraine (≤4%), irritability (3%), memory impairment (≤3%), drowsiness (2% to 3%), pain (3%), akathisia (≤2%), central nervous system stimulation (≤2%), paresthesia (≤2%), twitching (≤2%), dystonia (≥1%), abnormality in thinking (1%), depression

Dermatologic: Skin rash (1% to 8%), pruritus (2% to 4%), xeroderma (2%), urticaria (1% to 2%)

Endocrine & metabolic: Weight gain (9%), menstrual disease (2% to 5%), decreased libido (≤3%), hot flash (1% to 3%)

Gastrointestinal: Abdominal pain (2% to 9%), diarrhea (4% to 7%), flatulence (6%), anorexia (1% to 5%), dysgeusia (2% to 4%), increased appetite (2% to 4%), vomiting (≥1% to 4%), dyspepsia (3%), oral mucosa ulcer (2%), dysphagia (≤2%)

Genitourinary: Urinary frequency (≥1% to 5%), urinary urgency (≤2%), vaginal hemorrhage (≤2%), urinary tract infection (≤1%)

Hypersensitivity: Hypersensitivity reaction (1%)

Infection: Infection (8% to 9%)

Neuromuscular & skeletal: Myalgia (2% to 6%), arthralgia (4% to 5%), asthenia (4%), neck pain (2%), arthritis (≤2%), dyskinesia (≥1%)

Ophthalmic: Diplopia (≤3%)

Otic: Tinnitus (1% to 6%), auditory disturbance (5%)

Renal: Polyuria (≤1%)

Respiratory: Upper respiratory infection (9%), sinusitis (2% to 5%), cough (2% to 4%), increased cough (2% to 3%), epistaxis (2%), bronchitis (≤2%)

Miscellaneous: Accidental injury (2%), fever (1% to 2%)

<1%, postmarketing, and/or case reports: Abnormal stools, accommodation disturbance, acute myocardial infarction, aggressive behavior, akinesia, alopecia, amnesia, anaphylactic shock, anaphylaxis, anemia, angioedema, angle-closure glaucoma, aphasia, ataxia, atrioventricular block, bronchospasm, bruxism, cerebrovascular accident, change in prothrombin time, chills, colitis, coma, complete atrioventricular block, cutaneous lupus erythematosus (Hannah 2018), cystitis, deafness, delirium, delusion, depersonalization, derealization, drug-induced Parkinson disease, dry eye syndrome, dysarthria, dyspareunia, dysphoria, dysuria, ecchymoses, edema, EEG pattern changes, ejaculatory disorder, emotional lability, erythema multiforme, esophagitis, euphoria, exfoliative dermatitis, extrapyramidal reaction, extrasystoles, facial edema, gastric ulcer, gastroesophageal reflux disease, gastrointestinal hemorrhage, gingival hemorrhage, gingivitis, glossitis, glycosuria, gynecomastia, hallucination, hepatic injury, hepatic insufficiency, hepatitis, hirsutism, homicidal ideation, hyperglycemia, hyperkinetic muscle activity, hypertonia, hypoesthesia, hypoglycemia, hypokinesia, hypomania, hyponatremia, impotence, increased intraocular pressure, increased libido, increased thirst, inguinal hernia, intestinal perforation, jaundice, leukocytosis, leukopenia, lower limb cramp, lymphadenopathy, maculopapular rash, malaise, manic behavior, menopause, muscle rigidity, musculoskeletal chest pain, myasthenia, mydriasis, myoclonus, neuralgia, neuropathy, nonimmune anaphylaxis, orthostatic hypotension, painful erection, pancreatitis, pancytopenia, panic, paranoid ideation, peripheral edema, phlebitis, pneumonia, prostatic disease, psychiatric signs and symptoms, psychosis, pulmonary embolism, restlessness, rhabdomyolysis, salpingitis, sciatica, seizure (dose-related), serum sickness-like reaction, SIADH, sialorrhea, skin photosensitivity, Stevens-Johnson syndrome, stomatitis, subacute cutaneous lupus erythematosus (Hannah 2018), suicidal ideation, syncope, tardive dyskinesia, thrombocytopenia, tongue edema, type IV hypersensitivity reaction, urinary incontinence, urinary retention, vaginitis, vasodilation, vertigo

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Aniline Dye Allergy
• BuPROPion Allergy

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2A6 (minor), CYP2B6 (major), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (strong), OCT2

Drug Interactions Open Interactions

Abametapir: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Agents With Seizure Threshold Lowering Potential: BuPROPion may enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy

Ajmaline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Ajmaline. Risk C: Monitor therapy

Alcohol (Ethyl): BuPROPion may enhance the adverse/toxic effect of Alcohol (Ethyl). Specifically, alcohol tolerance may decrease during treatment. Alcohol (Ethyl) may enhance the adverse/toxic effect of BuPROPion. Specifically, seizure threshold may be lowered. Management: Patients receiving bupropion should be advised to minimize or avoid alcohol consumption due to possible lower alcohol tolerance, and lower seizure threshold associated with heavy alcohol consumption/abrupt discontinuation of heavy consumption. Risk D: Consider therapy modification

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy

Antihepaciviral Combination Products: May decrease the serum concentration of BuPROPion. Risk C: Monitor therapy

Anti-Parkinson Agents (Dopamine Agonist): May enhance the adverse/toxic effect of BuPROPion. Risk C: Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions are required for indications other than major depressive disorder. Dose reductions vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. See full interaction monograph for details. Risk D: Consider therapy modification

ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP2D6 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg) or if a CYP2D6 PM. Max dose is 441 mg if also taking strong CYP3A4 inhibitors. Risk D: Consider therapy modification

AtoMOXetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of AtoMOXetine. Management: Initiate atomoxetine at a reduced dose (patients who weigh up to 70 kg: 0.5 mg/kg/day; adults or patients who weigh 70 kg or more: 40 mg/day) in patients receiving a strong CYP2D6 inhibitor. Increase to usual target dose after 4 weeks if needed. Risk D: Consider therapy modification

Benzhydrocodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Benzhydrocodone. Risk C: Monitor therapy

Brexanolone: BuPROPion may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brexpiprazole: May enhance the adverse/toxic effect of BuPROPion. Specifically, the risk for seizures may be increased. BuPROPion may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual dose with bupropion; reduce to 25% of usual if used with both bupropion and a strong or moderate CYP3A4 inhibitor. These recommendations do not apply if treating major depressive disorder. Monitor for seizures. Risk D: Consider therapy modification

Carvedilol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Risk C: Monitor therapy

Chlorpheniramine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Chlorpheniramine. Risk C: Monitor therapy

Citalopram: BuPROPion may enhance the adverse/toxic effect of Citalopram. BuPROPion may increase the serum concentration of Citalopram. Management: Initiate citalopram at the lower end of the normal dose range in patients receiving bupropion and consider limiting the maximum citalopram adult dose to 20 mg/day during concomitant bupropion treatment. Monitor for citalopram toxicities. Risk D: Consider therapy modification

CloZAPine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy

CYP2B6 Inducers (Moderate): May decrease the serum concentration of BuPROPion. Risk C: Monitor therapy

CYP2B6 Inducers (Weak): May decrease the serum concentration of BuPROPion. Risk C: Monitor therapy

CYP2B6 Inhibitors (Weak): May increase the serum concentration of BuPROPion. Risk C: Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Risk C: Monitor therapy

Dapoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. Risk C: Monitor therapy

Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg, and the maximum single dose of deutetrabenazine should not exceed 18 mg, with concurrent use of a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

Dextromethorphan: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Dextromethorphan. Risk C: Monitor therapy

Digoxin: BuPROPion may decrease the serum concentration of Digoxin. Risk C: Monitor therapy

Dipyrone: May decrease the serum concentration of BuPROPion. Risk C: Monitor therapy

DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DULoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of DULoxetine. Risk C: Monitor therapy

Eliglustat: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider therapy modification

Escitalopram: BuPROPion may enhance the adverse/toxic effect of Escitalopram. Risk C: Monitor therapy

Fesoterodine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy

Flecainide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Flecainide. Risk C: Monitor therapy

FLUoxetine: May enhance the neuroexcitatory and/or seizure-potentiating effect of BuPROPion. BuPROPion may increase the serum concentration of FLUoxetine. Risk C: Monitor therapy

FluPHENAZine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of FluPHENAZine. Risk C: Monitor therapy

FluvoxaMINE: BuPROPion may enhance the adverse/toxic effect of FluvoxaMINE. Risk C: Monitor therapy

Galantamine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Galantamine. Risk C: Monitor therapy

Gefitinib: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Gefitinib. Risk C: Monitor therapy

Haloperidol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Haloperidol. Risk C: Monitor therapy

HYDROcodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Risk C: Monitor therapy

Iloperidone: May enhance the adverse/toxic effect of BuPROPion. Specifically, the risk for seizures may be increased. BuPROPion may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. BuPROPion may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. BuPROPion may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with bupropion. Monitor for increased iloperidone toxicities, including QTc prolongation and arrhythmias. Additionally, monitor for increased risk of seizures when these agents are combined. Risk D: Consider therapy modification

Indoramin: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Indoramin. Risk C: Monitor therapy

Iobenguane Radiopharmaceutical Products: BuPROPion may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer bupropion until at least 7 days after each iobenguane dose. Risk X: Avoid combination

Ioflupane I 123: BuPROPion may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Lofexidine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Lofexidine. Risk C: Monitor therapy

Lorcaserin (Withdrawn From US Market): BuPROPion may enhance the serotonergic effect of Lorcaserin (Withdrawn From US Market). This could result in serotonin syndrome. Management: Seek alternatives to this combination when possible. Risk D: Consider therapy modification

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Risk C: Monitor therapy

Maprotiline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Maprotiline. Risk C: Monitor therapy

Mequitazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mequitazine. Risk X: Avoid combination

Metoclopramide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoclopramide. Management: For gastroparesis: reduce metoclopramide dose to 5mg 4 times/day and limit to 20mg/day; nasal spray not recommended. For GERD: reduce metoclopramide dose to 5mg 4 times/day or to 10mg 3 times/day and limit to 30mg/day. Monitor for EPS when combined. Risk D: Consider therapy modification

Metoprolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoprolol. Risk C: Monitor therapy

Mexiletine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mexiletine. Risk C: Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of BuPROPion. Risk X: Avoid combination

Nebivolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy

Nicergoline: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Risk C: Monitor therapy

Oliceridine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Oliceridine. Risk C: Monitor therapy

Olmutinib: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy

PARoxetine: BuPROPion may enhance the adverse/toxic effect of PARoxetine. Risk C: Monitor therapy

Perhexiline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Perhexiline. Risk C: Monitor therapy

Perphenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Perphenazine. Risk C: Monitor therapy

Pimozide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Pitolisant: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients receiving strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg once daily and increase after 7 days to a maximum of 17.8 mg once daily. Risk D: Consider therapy modification

Primaquine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Primaquine. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Primaquine. Risk C: Monitor therapy

Propafenone: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Propafenone. Risk C: Monitor therapy

Propranolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Propranolol. Risk C: Monitor therapy

RisperiDONE: CYP2D6 Inhibitors (Strong) may increase the serum concentration of RisperiDONE. Management: Careful monitoring for risperidone toxicities and possible dose adjustment are recommended when combined with strong CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider therapy modification

Sertraline: BuPROPion may enhance the adverse/toxic effect of Sertraline. Risk C: Monitor therapy

Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Avoid concurrent use of strong CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with a reduced clinical effectiveness of tamoxifen. Risk D: Consider therapy modification

Tamsulosin: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy

Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Limit the tetrabenazine dose to 50 mg per day (25 mg per single dose) in patients taking strong CYP2D6 inhibitors. Risk D: Consider therapy modification

Thioridazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Thioridazine. Risk X: Avoid combination

Thiotepa: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Ophthalmic). Risk C: Monitor therapy

Timolol (Systemic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Systemic). Risk C: Monitor therapy

Tolterodine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Risk C: Monitor therapy

TraMADol: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Strong) may increase the serum concentration of TraMADol. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the neuroexcitatory and/or seizure-potentiating effect of BuPROPion. BuPROPion may increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy

Tropisetron: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tropisetron. Risk C: Monitor therapy

Valbenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Valbenazine. Management: Reduce valbenazine dose to 40 mg once daily when combined with a strong CYP2D6 inhibitor. Monitor for increased valbenazine effects/toxicities. Risk D: Consider therapy modification

Vilazodone: BuPROPion may enhance the adverse/toxic effect of Vilazodone. Risk C: Monitor therapy

Vortioxetine: BuPROPion may enhance the adverse/toxic effect of Vortioxetine. BuPROPion may increase the serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with bupropion. Following cessation of bupropion, the vortioxetine dose should be returned to the normal level. Risk D: Consider therapy modification

Zuclopenthixol: May enhance the adverse/toxic effect of BuPROPion. Specifically, the risk for seizures may be increased. BuPROPion may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy

Test Interactions

May interfere with urine detection of amphetamine/methamphetamine (false-positive). Decreased prolactin levels.

Genes of Interest

• Cytochrome P450 2B6

Monitoring Parameters

Body weight; mental status for depression, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; blood pressure (baseline and periodically especially when used in conjunction with nicotine transdermal replacement); renal and hepatic function

When used for the treatment of ADHD, thoroughly evaluate for cardiovascular risk. Monitor heart rate, blood pressure, and consider obtaining ECG prior to initiation (Vetter 2008).

Advanced Practitioners Physical Assessment/Monitoring

Perform careful cardiovascular, neurologic, and liver function assessments prior to initiating therapy. Monitor blood pressure and LFTs at beginning of therapy and periodically throughout. Monitor for clinical worsening; neuropsychiatric symptoms, such as changes in behavior, hostility, agitation, seizures, paranoia, hallucinations, insomnia, depression, and suicidality, especially at the beginning of therapy or when dose changes occur. Taper dosage slowly when discontinuing. Dosage adjustment indicated with hepatic impairment.

Nursing Physical Assessment/Monitoring

Monitor blood pressure at beginning of therapy and periodically throughout treatment. Monitor mental status for clinical worsening, such as changes in behavior, hostility, agitation, paranoia, hallucinations, depression, and suicidality, especially at the beginning of therapy or when dose changes occur.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral, as hydrochloride:

Generic: 75 mg, 100 mg

Tablet Extended Release 12 Hour, Oral, as hydrochloride:

Wellbutrin SR: 100 mg, 150 mg, 200 mg

Zyban: 150 mg [DSC]

Generic: 100 mg, 150 mg, 200 mg

Tablet Extended Release 24 Hour, Oral, as hydrobromide:

Aplenzin: 174 mg, 348 mg, 522 mg

Tablet Extended Release 24 Hour, Oral, as hydrochloride:

Forfivo XL: 450 mg

Wellbutrin XL: 150 mg, 300 mg

Generic: 150 mg, 300 mg, 450 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release 12 Hour, Oral, as hydrochloride:

Wellbutrin SR: 150 mg [contains fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake, polysorbate 80]

Zyban: 150 mg [contains fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake, polysorbate 80]

Generic: 100 mg, 150 mg

Tablet Extended Release 24 Hour, Oral, as hydrochloride:

Wellbutrin XL: 150 mg, 300 mg [contains alcohol, usp]

Generic: 150 mg, 300 mg

Anatomic Therapeutic Chemical (ATC) Classification

• N06AX12

Generic Available (US)

Yes

Pricing: US

Tablet, 12-hour (buPROPion HCl ER (Smoking Det) Oral)

150 mg (per each): $1.94

Tablet, 12-hour (buPROPion HCl ER (SR) Oral)

100 mg (per each): $1.69

150 mg (per each): $0.70 - $1.94

200 mg (per each): $3.38 - $3.83

Tablet, 12-hour (Wellbutrin SR Oral)

100 mg (per each): $8.31

150 mg (per each): $8.91

200 mg (per each): $16.54

Tablet, 24-hour (Aplenzin Oral)

174 mg (per each): $59.55

348 mg (per each): $78.50

522 mg (per each): $178.64

Tablet, 24-hour (buPROPion HCl ER (XL) Oral)

150 mg (per each): $0.52 - $5.22

300 mg (per each): $0.55 - $19.33

450 mg (per each): $16.07 - $16.76

Tablet, 24-hour (Forfivo XL Oral)

450 mg (per each): $17.88

Tablet, 24-hour (Wellbutrin XL Oral)

150 mg (per each): $58.79

300 mg (per each): $77.61

Tablets (buPROPion HCl Oral)

75 mg (per each): $0.64 - $1.55

100 mg (per each): $0.86 - $1.97

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Aminoketone antidepressant structurally different from all other marketed antidepressants; like other antidepressants the mechanism of bupropion's activity is not fully understood. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine, and does not inhibit monoamine oxidase or the reuptake of serotonin. Metabolite inhibits the reuptake of norepinephrine. The primary mechanism of action is thought to be dopaminergic and/or noradrenergic.

Pharmacodynamics/Kinetics

Onset of action: Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009).

Duration of action: 1 to 2 days

Absorption: Rapid

Distribution: Vd: ~20 to 47 L/kg (Laizure 1985)

Protein binding: 84%

Metabolism: Extensively hepatic via CYP2B6 to hydroxybupropion; non-CYP-mediated metabolism to erythrohydrobupropion and threohydrobupropion. Metabolite activity ranges from 20% to 50% potency of bupropion. Bupropion also undergoes oxidation to form the glycine conjugate of meta-chlorobenzoic acid, the major urinary metabolite.

Half-life:

Distribution: 3 to 4 hours

Elimination:

Hydrochloride salt: ~21 hours after chronic dosing (± 9 hours); Metabolites (after a single dose): Hydroxybupropion: 20 ± 5 hours; Erythrohydrobupropion: 33 ± 10 hours; Threohydrobupropion: 37 ± 13 hours

Hydrobromide salt: 21 ± 7 hours; Metabolites: Hydroxybupropion: 24 ± 5 hours; Erythrohydrobupropion: 31 ± 8 hours; Threohydrobupropion: 51 ± 9 hours

Time to peak, serum:

Bupropion: Immediate release: Within 2 hours; 12-hour extended release (sustained release): Within 3 hours; 24-hour extended release: ~5 hours; 12 hours (fed)

Metabolite: Hydroxybupropion: Immediate release: ~3 hours; Extended release: ~6 to 7 hours

Excretion: Urine (87%, primarily as metabolites); feces (10%, primarily as metabolites)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Elimination of bupropion and/or major metabolites may be reduced.

Hepatic function impairment: Elimination of hydroxybupropion is reduced in patients with alcoholic liver disease. Bupropion Cmax increased 70%, AUC increased 3-fold, and mean half-life increased to 29 hours in patients with severe hepatic impairment. Mean half-life for active metabolites increased 2- to 5-fold in patients with severe hepatic impairment.

Geriatric: May be at risk of accumulation of bupropion and its metabolites.

Gender: AUC was approximately 13% higher in men.

Local Anesthetic/Vasoconstrictor Precautions

Part of the mechanism of bupropion is to block reuptake of norepinephrine along with dopamine. Because of the potential for norepinephrine elevation within CNS synapses, it is suggested that vasoconstrictor be administered with caution and to monitor vital signs in dental patients taking antidepressants that affect norepinephrine in this way.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Significant xerostomia (normal salivary flow resumes with discontinuation); infrequent occurrence of abnormal taste, oral mucosal ulcers; rare occurrence of stomatitis, tongue edema, gingivitis, glossitis.

Effects on Bleeding

Rare occurrences of thrombocytopenia and gingival hemorrhage.

Related Information

• Antidepressant Receptor Profile
• Comparison of Antidepressant Adverse Effects
• First-Line Smoking Cessation Products
• Oral Medications That Should Not Be Crushed or Altered
• Relative Infant Dose

Pharmacotherapy Pearls

Risk of seizures: When using bupropion hydrochloride immediate release tablets, seizure risk is increased at total daily dosage >450 mg, individual dosages >150 mg, or by sudden, large increments in dose. Data for the immediate-release formulation of bupropion revealed a seizure incidence of 0.4% in patients treated at doses in the 300 to 450 mg/day range. The estimated seizure incidence increases almost 10-fold between 450 mg and 600 mg per day. Data for the 12-hour extended release (sustained release) dosage form revealed a seizure incidence of 0.1% in patients treated at a dosage range of 100 to 300 mg/day, and increases to ~0.4% at the maximum recommended dose of 400 mg/day.

Index Terms

Budeprion SR; Bupropion HCl; Bupropion Hydrobromide; Bupropion Hydrochloride

FDA Approval Date

December 30, 1985

References

ACOG Committee on Practice Bulletins--Obstetrics, "ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists Number 92, April 2008 (Replaces Practice Bulletin Number 87, November 2007). Use of Psychiatric Medications During Pregnancy and Lactation," Obstet Gynecol, 2008, 111(4):1001-20.[PubMed 18378767]

American Academy of Pediatrics/American Heart Association Clarification of Statement on Cardiovascular Evaluation and Monitoring of Children and Adolescents With Heart Disease Receiving Medications for ADHD; available at: http://americanheart.mediaroon.com/index.php?s=43&item=422.

American College of Obstetricians and Gynecologists (ACOG) Committee on Underserved Women; Committee on Obstetric Practice. Committee opinion no. 721: smoking cessation during pregnancy. Obstet Gynecol. 2017;130(4):e200-e204.[PubMed 28937573]

American Psychiatric Association (APA). Treatment recommendations for patients with major depressive disorder. 3rd ed. May 2010. Available at http://www.psychiatryonline.com/pracGuide/pracGuideTopic_7.aspx

American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder. 2nd ed. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/bipolar.pdf. Published April 2002.

American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. 3rd ed. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Published November 2010.

Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52.[PubMed 27060684]

Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016;S0140-6736(16)30272-0. doi: 10.1016/S0140-6736(16)30272-0.[PubMed 27116918 ]10.1016/S0140-6736(16)30272-0

Aplenzin (bupropion hydrobromide) [prescribing information]. Bridgewater, NJ: Bausch Health US, LLC; June 2020.

Barrickman LL, Petty PJ, Allen AJ, et al. Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1995;34(5):649-657.[PubMed 7775360]

Bauer M, Pfennig A, Severus E, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry. 2013;14(5):334-385.[PubMed 23879318]

Berle JO, Spigset O. Antidepressant use during breastfeeding. Curr Womens Health Rev. 2011;7(1):28-34.[PubMed 22299006]

Bond DJ, Hadjipavlou G, Lam RW, et al; Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force. The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force recommendations for the management of patients with mood disorders and comorbid attention-deficit/hyperactivity disorder. Ann Clin Psychiatry. 2012;24(1):23-37.[PubMed 22303520]

Brent D, Bukstein O, Solanto MV. Approach to treating attention deficit hyperactivity disorder in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 8, 2019.

Bukstein O. Pharmacotherapy for attention deficit hyperactivity disorder in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2019.

Bupropion hydrochloride tablets [prescribing information]. East Brunswick, NJ: Avet Pharmaceuticals Inc; April 2020.

Burke MJ, Preskorn SH. Therapeutic drug monitoring of antidepressants: cost implications and relevance to clinical practice. Clin Pharmacokinet. 1999;37(2):147-165.[PubMed 10496302]

Chaudron LH and Schoenecker CJ, "Bupropion and Breastfeeding: A Case of a Possible Infant Seizure," J Clin Psychiatry, 2004, 65(6):881-2.[PubMed 15291673]

Cinciripini PM, Robinson JD, Karam-Hage M, et al. Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal. JAMA Psychiatry. 2013;70(5):522-533.[PubMed 23536105]

Clayton AH, Warnock JK, Kornstein SG, Pinkerton R, Sheldon-Keller A, McGarvey EL. A placebo-controlled trial of bupropion SR as an antidote for selective serotonin reuptake inhibitor-induced sexual dysfunction. J Clin Psychiatry. 2004;65(1):62-67.[PubMed 14744170]

Cochren BE. Splitting bupropion extended-release tablets. Am J Health-Syst Pharm. 1999;56(6):575.[PubMed 10192696]

Conners CK, Casat CD, Gualtieri CT, et al. Bupropion hydrochloride in attention deficit disorder with hyperactivity. J Am Acad Child Adolesc Psychiatry. 1996;35(10):1314-1321.[PubMed 8885585]

Davidson J, “Seizures and Bupropion: A Review,” J Clin Psychiatry, 1989, 50(7):256-61.[PubMed 2500425]

Davis MF, Miller HS, and Nolan PE Jr, "Bupropion Levels in Breast Milk for 4 Mother-Infant Pairs: More Answers to Lingering Questions," J Clin Psychiatry, 2009, 70(2):297-8.[PubMed 19265649]

Daviss WB, Bentivoglio P, Racusin R, et al, "Bupropion Sustained Release in Adolescents With Comorbid Attention-Deficit/Hyperactivity Disorder and Depression," J Am Acad Child Adolesc Psychiatry, 2001, 40(3):307-14.[PubMed 11288772]

Daviss WB, Perel JM, Birmaher B, et al, "Steady-State Clinical Pharmacokinetics of Bupropion Extended-Release in Youths," J Am Acad Child Adolesc Psychiatry, 2006, 45(12):1503-9.[PubMed 17135996]

Daviss WB, Perel JM, Rudolph GR, et al. Steady-state pharmacokinetics of bupropion SR in juvenile patients. J Am Acad Child Adolesc Psychiatry. 2005;44(4):349-357.[PubMed 15782082]

Dopheide JA, "Recognizing and Treating Depression in Children and Adolescents," Am J Health Syst Pharm, 2006, 63(3):233-43.[PubMed 16434782]

Dopheide JA, Pliszka SR. Attention-deficit-hyperactivity disorder: an update. Pharmacotherapy. 2009;29(6):656-679.[PubMed 19476419]

Earhart AD, Patrikeeva S, Wang X, et al, "Transplacental Transfer and Metabolism of Bupropion," J Matern Fetal Neonatal Med, 2010, 23(5):409-16.[PubMed 19658039]

Fava M. Prospective studies of adverse events related to antidepressant discontinuation. J Clin Psychiatry. 2006;67(Suppl 4):14-21.[PubMed 16683858]

Fiore M, Jaen CR, Baker TB, et al, “A Clinical Practice Guideline for Treating Tobacco Use and Dependence: 2008 Update. A U.S. Public Health Service Report,” Am J Prev Med, 2008, 35(2):158-76. https://www.ahrq.gov/sites/default/files/wysiwyg/professionals/clinicians-providers/guidelines-recommendations/tobacco/clinicians/update/treating_tobacco_use08.pdf.[PubMed 18617085]

Fokina VM, West H, Oncken C, et al. Bupropion therapy during pregnancy: the drug and its major metabolites in umbilical cord plasma and amniotic fluid. Am J Obstet Gynecol. 2016;215(4):497.[PubMed 27180885]

Forfivo XL (bupropion hydrochloride) [prescribing information]. Pine Brook, NJ: Almatica Pharma, Inc; December 2019.

Goodnick PJ. Blood levels and acute response to bupropion. Am J Psychiatry. 1992;149(3):399-400.[PubMed 1536282]

Grossman F, Potter WZ, Brown EA, Maislin G. A double-blind study comparing idazoxan and bupropion in bipolar depressed patients. J Affect Disord. 1999;56(2-3):237-243.[PubMed 10701483]

Grunze H, Vieta E, Goodwin GM; WFSBP Task Force on Treatment Guidelines for Bipolar Disorder. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2010 on the treatment of acute bipolar depression. World J Biol Psychiatry. 2010;11(2):81-109. doi: 10.3109/15622970903555881.[PubMed 20148751]

Grunze H, Vieta E, Goodwin GM, et al; Members of the WFSBP Task Force on Bipolar Affective Disorders. The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the biological treatment of bipolar disorders: acute and long-term treatment of mixed states in bipolar disorder. World J Biol Psychiatry. 2018;19(1):2-58. doi: 10.1080/15622975.2017.1384850.[PubMed 29098925]

Haas JS, Kaplan CP, Barenboim D, et al, "Bupropion in Breast Milk: An Exposure Assessment for Potential Treatment to Prevent Post-Partum Tobacco Use," Tob Control, 2004, 13(1):52-6.[PubMed 14985597]

Hack S, "Pediatric Bupropion-Induced Serum Sickness Like Reaction," J Child Adolesc Psychopharmacol, 2004, 14(3):478-80.[PubMed 15650506]

Haddad PM. Antidepressant discontinuation syndromes. Drug Saf. 2001;24(3):183-197.[PubMed 11347722]

Hale TW, Kendall-Tackett K, Cong Z, et al, "Discontinuation Syndrome in Newborns Whose Mothers Took Antidepressants While Pregnant or Breastfeeding," Breastfeed Med, 2010, 5(6):283-8.[PubMed 20807106]

Hannah CE, Little AJ, Wanat KA, Fairley JA. Drug-induced cutaneous lupus erythematosus: a case series of five patients with bupropion-associated disease [published online September 14, 2018]. J Clin Rheumatol.[PubMed 30222626]

Hughes JR, Stead LF, Hartmann-Boyce J, Cahill K, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014;(1):CD000031. doi: 10.1002/14651858.CD000031.pub4.[PubMed 24402784]

Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126.[PubMed 10891521]

Jafarinia M, Mohammadi MR, Modabbernia A, et al. Bupropion versus methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder: randomized double-blind study. Hum Psychopharmacol. 2012;27(4):411-418. doi: 10.1002/hup.2242.[PubMed 22806822]

Jennison TA, Brown P, Crossett J, et al, “A High-Performance Liquid Chromatographic Method for Quantitating Bupropion in Human Plasma or Serum,” J Anal Toxicol, 1995, 19(2):69-72.[PubMed 7769789]

Laizure SC, DeVane CL, Stewart JT, et al, “Pharmacokinetics of Bupropion and Its Major Basic Metabolites in Normal Subjects After a Single Dose,” Clin Pharmacol Ther, 1985, 38(5):586-9.[PubMed 3931955]

Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;(445):1-28.[PubMed 26344706]

Leverich GS, Altshuler LL, Frye MA, et al, “Risk of Switch in Mood Polarity to Hypomania or Mania in Patients with Bipolar Depression During Acute and Continuation Trials of Venlafaxine, Sertraline, and Bupropion as Adjuncts to Mood Stabilizers,” Am J Psychiatry, 2006, 163(2):232-9.[PubMed 16449476]

Li DJ, Tseng PT, Chen YW, Wu CK, Lin PY. Significant treatment effect of bupropion in patients with bipolar disorder but similar phase-shifting rate as other antidepressants: a meta-analysis following the PRISMA guidelines. Medicine (Baltimore). 2016;95(13):e3165. doi: 10.1097/MD.0000000000003165.[PubMed 27043678]

MacQueen GM, Frey BN, Ismail Z, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 6. Special populations: youth, women, and the elderly. Can J Psychiatry. 2016;61(9):588-603.[PubMed 27486149]

Maneeton N, Maneeton B, Srisurapanont M, Martin SD. Bupropion for adults with attention-deficit hyperactivity disorder: meta-analysis of randomized, placebo-controlled trials. Psychiatry Clin Neurosci. 2011;65(7):611-617. doi: 10.1111/j.1440-1819.2011.02264.x.[PubMed 22176279]

Mauri MC, Fiorentini A, Paletta S, Altamura AC. Pharmacokinetics of antidepressants in patients with hepatic impairment. Clin Pharmacokinet. 2014;53(12):1069-1081. doi:10.1007/s40262-014-0187-5[PubMed 25248846]

McIntyre RS, Mancini DA, McCann S, Srinivasan J, Sagman D, Kennedy SH. Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study. Bipolar Disord. 2002;4(3):207-213.[PubMed 12180276]

Mullish BH, Kabir MS, Thursz MR, Dhar A. Review article: depression and the use of antidepressants in patients with chronic liver disease or liver transplantation. Aliment Pharmacol Ther. 2014;40(8):880-892. doi:10.1111/apt.12925[PubMed 25175904]

Muramoto ML, Leischow SJ, Sherrill D, et al, "Randomized, Double-Blind, Placebo-Controlled trial of 2 Dosages of Sustained-Release Bupropion for Adolescent Smoking Cessation," Arch Pediatr Adolesc Med, 2007, 161(11):1068-74.[PubMed 17984409]

Nelson JC and Devanand DP, "A Systematic Review and Meta-Analysis of Placebo-Controlled Antidepressant Studies in People With Depression and Dementia," J Am Geriatr Soc, 2011, 59(4):577-85.[PubMed 21453380]

Neuman G, Colantonio D, Delaney S, Szynkaruk M, Ito S. Bupropion and escitalopram during lactation. Ann Pharmacother. 2014;48(7):928-931.[PubMed 24732787]

Papakostas GI, Perlis RH, Scalia MJ, Petersen TJ, Fava M. A meta-analysis of early sustained response rates between antidepressants and placebo for the treatment of major depressive disorder. J Clin Psychopharmacol. 2006;26(1):56-60. doi:10.1097/01.jcp.0000195042.62724.76[PubMed 16415707]

Pass SE and Simpson RW, “Discontinuation and Reinstitution of Medications During the Perioperative Period,” Am J Health Syst Pharm, 2004, 61(9):899-912.[PubMed 15156966]

Pliszka S; AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921.[PubMed 17581453]

Pliszka SR, Crismon ML, Hughes CW, et al, "The Texas Children's Medication Algorithm Project: Revision of the Algorithm for Pharmacotherapy of ADHD," J Am Acad Child Adolesc Psychiatry, 2006, 45(6):642-57.[PubMed 16721314]

Posternak MA, Zimmerman M. Is there a delay in the antidepressant effect? A meta-analysis. J Clin Psychiatry. 2005;66(2):148-158. doi:10.4088/jcp.v66n0201[PubMed 15704999]

Preskorn SH. Antidepressant response and plasma concentrations of bupropion. J Clin Psychiatry. 1983;44(5 Pt 2):137-139.[PubMed 6406443]

Reimherr FW, Hedges DW, Strong RE, Marchant BK, Williams ED. Bupropion SR in adults with ADHD: a short-term, placebo-controlled trial. Neuropsychiatr Dis Treat. 2005;1(3):245-251.[PubMed 18568102]

Riggs PD, Leon SL, Mikulich SK, et al, “An Open Trial of Bupropion for ADHD in Adolescents With Substance Use Disorders and Conduct Disorder,” J Am Acad Child Adolesc Psychiatry, 1998, 37(12):1271-8.[PubMed 9847499]

Sachs HC, Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013;132(3):e796-809.[PubMed 23979084]

Safarinejad MR. Reversal of SSRI-induced female sexual dysfunction by adjunctive bupropion in menstruating women: a double-blind, placebo-controlled and randomized study. J Psychopharmacol. 2011;25(3):370-378. doi: 10.1177/0269881109351966.[PubMed 20080928]

Shelton RC. Steps following attainment of remission: discontinuation of antidepressant therapy. Prim Care Companion J Clin Psychiatry. 2001;3(4):168-174.[PubMed 15014601]

Siu AL; US Preventive Services Task Force. Behavioral and pharmacotherapy interventions for tobacco smoking cessation in adults, including pregnant women: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;163(8):622-634. doi: 10.7326/M15-2023.[PubMed 26389730]

Sriraman NK, Melvin K, Meltzer-Brody S. ABM clinical protocol #18: use of antidepressants in breastfeeding mothers. Breastfeed Med. 2015;10(6):290-299.[PubMed 26204124]

Szegedi A, Jansen WT, van Willigenburg AP, van der Meulen E, Stassen HH, Thase ME. Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry. 2009;70(3):344-353. doi:10.4088/jcp.07m03780[PubMed 19254516]

Turpeinen M, Koivuviita N, Tolonen A, et al, "Effect of Renal Impairment on the Pharmacokinetics of Bupropion and Its Metabolites," Br J Clin Pharmacol, 2007, 64(2):165-73.[PubMed 17335546]

Van Wyck FJ, Manberg PJ, Miller LL, et al, “Overview of Clinically Significant Adverse Reactions to Bupropion,” J Clin Psychiatry, 1983, 44(5 Pt 2):191-6.[PubMed 6406456]

Vetter VL, Elia J, Erickson CH, et al; American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee; American Heart Association Council on Cardiovascular Nursing. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder [corrected]: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation. 2008;117(18):2407-2423.[PubMed 18427125]

Wagner KD, "Pharmacotherapy for Major Depression in Children and Adolescents," Prog Neuropsychopharmacol Biol Psychiatry, 2005, 29(5):819-26.[PubMed 15908090]

Warner CH, Bobo W, Warner C, Reid S, Rachal J. Antidepressant discontinuation syndrome. Am Fam Physician. 2006;74(3):449-456.[PubMed 16913164]

Wellbutrin (bupropion hydrochloride) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; November 2019.

Wellbutrin SR (bupropion hydrochloride) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; May 2017.

Wellbutrin SR (bupropion hydrochloride) [product monograph]. Laval, Quebec, Canada: Valeant Canada LP; July 2020.

Wellbutrin XL (bupropion hydrochloride) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; May 2017.

Wellbutrin XL (bupropion hydrochloride) [product monograph]. Laval, Quebec, Canada: Valeant Canada LP; July 2020.

Wilens TE, Haight BR, Horrigan JP, et al. Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Biol Psychiatry. 2005;57(7):793-801.[PubMed 15820237]

Wilens TE, Spencer TJ, Biederman J, et al. A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry. 2001;158(2):282-288.[PubMed 11156812]

Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97-170. doi: 10.1111/bdi.12609.[PubMed 29536616]

Yonkers KA, Wisner KL, Stewart DE, et al, “The Management of Depression During Pregnancy: A Report From the American Psychiatric Association and the American College of Obstetricians and Gynecologists,” Obstet Gynecol, 2009, 114(3):703-13.[PubMed 19701065]

Zyban (bupropion hydrochloride) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; July 2019.

Zyban (bupropion hydrochloride) [product monograph]. Laval, Quebec, Canada: Valeant Canada LP; July 2020.

Brand Names: International

Abstain SR (EG); Betetrim (TW); Bupep SR (IN); Buprotrin (TW); Buxon (CL); Deppreo (VN); Elontril (EE, ES, HU, LT, RO, SK); Fumipan (EG); Funnix (TW); Le Fu Ting (CN); Nicopion (KR); Nicostop (VN); Odranal (AR, CO); Prewell (TW); Prexaton (AU); Quomen (TH); Vixadep (EG); Wellbutrin (MX, PE, PY, TW, VE); Wellbutrin Retard (IS, SK); Wellbutrin SR (AR, BB, BM, BS, CL, EC, HK, HU, JM, KR, LV, MY, SG, UY); Wellbutrin XL (BB, BH, BM, BS, CO, CR, DO, EC, GT, HK, HN, JM, KR, KW, NI, PA, PE, QA, SA, SV, TH, TW); Wellbutrin XR (CY, HR, IL, LU, MT, SI, TR); Wellinta (EG); Yue Ting (CN); Zyban (AE, AT, BB, BE, BG, BM, BR, BS, BZ, CH, CY, CZ, DE, DK, FI, FR, GB, GR, GY, IE, IL, IN, IS, IT, JM, MT, NL, NO, NZ, PL, PR, PT, RO, SA, SE, SI, SR, TR, TT); Zyban LP (FR); Zyban SR (BH, KW, QA, SG); Zyban Sustained Release (AU); Zylexx SR (PK); Zyntabac (ES)

Last Updated 10/14/20