Brand names: Wellbutrin, Zyban
Drug class: Antidepressants, Miscellaneous
- Smoking Deterrents
- Deterrents, Smoking
VA class: CN609
Chemical name: ±-1-(3-Chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone Hydrochloride
Molecular formula: C₁₃H₁₈ClNO•ClH
CAS number: 31677-93-7

Medically reviewed by Drugs.com on Jan 26, 2023. Written by ASHP.

Introduction

Antidepressant and smoking deterrent; aminoketone derivative.

Uses for buPROPion

Major Depressive Disorder

Treatment of major depressive disorder.

May be useful (alone or in combination with other antidepressants) in patients with refractory depression.

Seasonal Affective Disorder

Prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD; also referred to as winter depression).

Smoking Cessation

Adjunct in the cessation of smoking (alone or in combination with nicotine replacement therapy). (See Hypertension under Cautions and also see Smoking Cessation and Specific Drugs under Interactions.)

US Public Health Service (USPHS) guideline for the treatment of tobacco use and dependence recommends bupropion (as extended-release tablets) as one of several first-line drugs that may reliably increase long-term smoking abstinence rates. For additional information, consult the most current USPHS clinical practice guideline available at [Web]

Depression Associated with Bipolar Disorder

Treatment of patients with bipolar depression^{† [off-label]} (bipolar disorder, depressive episode).

American Psychiatric Association (APA) considers bupropion one of several second-line agents for use when first-line agents are ineffective or not tolerated.

Attention Deficit Hyperactivity Disorder (ADHD)

Used in a limited number of children and adults in the management of ADHD^{† [off-label]}.

Panic Disorder

Ineffective in the treatment of panic disorder and concomitant phobic disorder^{† [off-label]}, but may improve symptoms of panic and depression in patients with major depression who have superimposed panic symptoms.

Bulimia Nervosa

Not recommended by APA for bulimia nervosa^{† [off-label]} because associated with seizures in purging bulimic patients.

buPROPion Dosage and Administration

General

• Appropriately monitor and closely observe all patients receiving bupropion for any indication for clinical worsening, suicidality, or unusual changes in behavior, particularly during initial therapy or following any change (increase or decrease) in dosage. (See Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders in Boxed Warning and also under Cautions.)

• Monitor all patients receiving bupropion for smoking cessation for serious neuropsychiatric symptoms or worsening of preexisting psychiatric illness. (See Neuropsychiatric Symptoms and Suicidality in Smoking Cessation Treatment under Cautions.)

Major Depressive Disorder

• Increase dosages gradually to minimize the risk of seizures and other adverse effects; do not exceed recommended maximum individual doses or daily dosages. (See Prescribing Limits under Dosage and Administration and also see Seizures under Cautions.)

• Maximum antidepressant effects of therapy may not be evident until ≥4 weeks of treatment.

• Sustained therapy may be required; monitor periodically for need for continued therapy.

Administration

Oral Administration

Conventional Tablets

Initially, administer orally twice daily in the morning and evening, then increase to 3 times daily, preferably with 6 or more hours separating doses (e.g., in the morning, at midday, and in the evening).

Dosages ≥300 mg should be administered as divided doses that do not exceed 150 mg per dose. If components of a larger dosage include 4 whole tablets of 100 mg each, administer the divided doses 4 times daily separated by 4 or more hours so that no individual dose exceeds 150 mg.

Avoid bedtime administration of evening dose to decrease incidence of insomnia.

Extended-release Tablets

Extended-release, film-coated tablets (e.g., Wellbutrin SR): Initially, administer orally once daily in the morning, then increase to twice daily, in the morning and evening. Dosages >150 mg should be administered as divided doses twice daily, preferably with 8 or more hours separating the doses. Avoid bedtime administration of evening dose to decrease incidence of insomnia.

Extended-release, film-coated tablets (e.g., Zyban): Administer orally once daily for the first 3 days, then usually increase to twice daily administration with 8 or more hours separating the doses. Avoid bedtime administration of evening dose to decrease incidence of insomnia.

Extended-release tablets (Wellbutrin XL): Administer orally once daily in the morning, with an interval of 24 hours separating the doses.

Do not chew, divide, or crush the extended-release tablets (e.g., Zyban, Wellbutrin SR, Wellbutrin XL); tablets should be swallowed whole.

The shell of the extended-release tablet (Wellbutrin XL) does not dissolve and may be passed in the stool.

Dosage

Available as bupropion hydrochloride; dosage expressed in terms of the salt.

Pediatric Patients

ADHD† [off-label]

Oral

Children weighing ≥20 kg: Initially, 1 mg/kg daily in 2–3 divided doses. After 3 days, titrate up to 3 mg/kg daily in 2–3 divided doses by day 7, then up to 6 mg/kg daily in 2–3 divided doses or 300 mg (whichever is smaller) by third week of therapy.

Alternatively, may give initial dose of 37.5 or 50 mg twice daily with titration over 2 weeks up to a maximum of 250 mg daily (300–400 mg daily in adolescents).

Pediatric dosage for ADHD generally has ranged from 50–100 mg 3 times daily for conventional tablets or 100–150 mg twice daily for extended-release tablets.

Adults

Major Depression

Therapy with Conventional Tablets

Oral

Initially, 100 mg twice daily. Alternatively, dosage may be initiated at 75 mg 3 times daily.

If clinical improvement not apparent after >3 days, may increase to 100 mg 3 times daily.

Dosages >300 mg should not be considered until completion of several weeks of therapy; if no improvement is apparent, then the dosage may be increased to 150 mg 3 times daily. Dosage should not be increased by more than 100 mg every 3 days.

If no improvement after appropriate trial at 450 mg daily, the drug should be discontinued.

Therapy with Extended-release Tablets

Oral

Extended-release, film-coated tablets (e.g., Wellbutrin SR): Initially, 150 mg once daily in the morning. If tolerated, may increase to 150 mg twice daily as early as fourth day of therapy. Dosages >300 mg daily should not be considered until completion of several weeks of therapy; then, if no apparent improvement, may increase dosage to 200 mg twice daily.

Extended-release tablets (Wellbutrin XL): Initially, 150 mg once daily. If tolerated, may increase to 300 mg once daily as early as fourth day of therapy. Dosages >300 mg should not be considered until completion of several weeks of therapy; then, if no apparent improvement, may increase dosage to 450 mg once daily.

When switching from conventional or extended-release, film-coated tablets (e.g., Wellbutrin SR) to extended-release tablets (Wellbutrin XL), administer same total daily dose when possible.

Seasonal Affective Disorder

Therapy with Extended-release Tablets

Oral

Extended-release tablets (Wellbutrin XL): Initiate therapy in autumn prior to onset of depressive symptoms; continue treatment through the winter and taper and discontinue in early spring. Individualize timing of initiation and duration of therapy based on patient’s historical pattern of seasonal depressive episodes.

Initially, 150 mg once daily in the morning. If tolerated, may increase dosage after 1 week to 300 mg once daily. If this dosage is not tolerated, reduce dosage to 150 mg once daily.

Usual target dosage: 300 mg once daily in the morning.

For patients receiving 300 mg once daily during the autumn-winter period, taper dosage to 150 mg once daily for 2 weeks prior to discontinuance.

Smoking Cessation

Therapy with Extended-release, Film-coated Tablets

Oral

Initially, 150 mg daily for the first 3 days of therapy. Initiate 1–2 weeks prior to discontinuance of cigarette smoking.

Maintenance, 150 mg twice daily. Continue therapy for 7–12 weeks; evaluate need for prolonged therapy after that period based on individual patient assessment.

Cessation of smoking is unlikely in patients who do not show substantial progress toward abstinence after 7 weeks of therapy, so such therapy should be discontinued at that time in these patients.

Combination Therapy with Extended-release Tablets and Transdermal Nicotine Patches

Oral

Initially, 150 mg daily, and after 3 days increase to 150 mg twice daily while still smoking.

After about 1 week of therapy, when the patient is scheduled to stop smoking, initiate transdermal nicotine therapy at a dosage of 21 mg/24 hours.

Taper transdermal nicotine to 14, then to 7 mg/24 hours during the eighth and ninth weeks of therapy, respectively.

Depression Associated With Bipolar Disorder†

Oral

Dosages generally range from 75–400 mg in conjunction with a mood-stabilizing agent (e.g., carbamazepine, lithium, valproate).

ADHD†

Therapy with Conventional Tablets

Oral

Initially, 150 mg daily. May be titrated up to 450 mg daily.

Prescribing Limits

Adults

Major Depression

Oral

Conventional tablets: Maximum 450 mg daily (not >150 mg per dose).

Extended-release, film-coated tablets (e.g., Wellbutrin SR): Maximum 400 mg daily (not >200 mg per dose).

Extended-release tablets (Wellbutrin XL): Maximum 450 mg daily.

Seasonal Affective Disorder

Oral

Extended-release tablets (e.g., Wellbutrin XL): Dosages >300 mg daily have not been studied.

Smoking Cessation

Oral

Extended-release, film-coated tablets (e.g., Zyban): 300 mg daily (not >150 mg per dose).

Special Populations

Hepatic Impairment

Smoking cessation in patients with severe hepatic cirrhosis: Maximum 150 mg every other day as extended-release, film-coated tablets (e.g., Zyban).

Major depression, seasonal affective disorder, or smoking cessation in patients with mild to moderate hepatic impairment (e.g., mild to moderate hepatic cirrhosis): Reduce dosage and/or frequency of administration as required. (See Hepatic Impairment under Cautions.)

Renal Impairment

Active metabolites may accumulate; reduce dosage and/or frequency of administration as required. (See Renal Impairment under Cautions.)

Smoking cessation in patients undergoing hemodialysis: Some clinicians recommend a dosage of 150 mg every 3 days as extended-release, film-coated tablets (e.g., Zyban).

Cautions for buPROPion

Contraindications

• Seizure disorders.

• Current or past diagnosis of anorexia nervosa or bulimia.

• Contraindicated in patients receiving any other bupropion formulation (e.g., for smoking cessation, antidepressant use) because risk of seizures is dose-dependent.

• Patients undergoing abrupt discontinuance of alcohol or sedatives (including benzodiazepines).

• Patients currently receiving, or having recently received (i.e., within 2 weeks), MAO inhibitor therapy.

• Hypersensitivity to the drug or any ingredient in the formulation.

Warnings/Precautions

Warnings

Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs. However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

Appropriately monitor and closely observe patients receiving bupropion for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments. (See Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders in Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality. Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms. (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions (e.g., pruritus, urticaria, angioedema, dyspnea) have been reported; however, causality has not been established. Postmarketing reports include erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock.

Possible arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity.

General Precautions

Neuropsychiatric Symptoms and Suicidality in Smoking Cessation Treatment

Serious neuropsychiatric symptoms, including mood changes (e.g., depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, and panic as well as suicidal ideation, suicide attempt, and completed suicide, reported in patients receiving bupropion or varenicline for smoking cessation; has occurred in patients with or without psychiatric history.

Additional analyses and studies, including a large randomized controlled study in more than 8000 patients, indicate that risk is lower than previously thought and comparable to nicotine replacement therapy or placebo. However, there is evidence indicating patients with a preexisting psychiatric illness (e.g., depression, anxiety disorder, schizophrenia) may be more likely to experience such events.

Although risk remains, particularly in individuals with current or past psychiatric illnesses, patients generally do not experience serious consequences (e.g., hospitalization); therefore, benefits of smoking cessation (e.g., reduced risk of developing pulmonary disease, cardiovascular disease, and cancer) continue to outweigh risks of these cessation drugs.

Monitor patients for neuropsychiatric symptoms or for worsening of preexisting psychiatric conditions. Discontinue bupropion in patients who develop agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient or who develop suicidal ideation or suicidal behavior. Provide ongoing monitoring and supportive care until symptoms resolve.

Seizures

Seizures reported; risk of seizures may be higher with sudden and large increases in dosage. (See Dosage and Administration.)

Risk factors include patient factors (e.g., history of head trauma or prior seizure, CNS tumor, presence of severe hepatic cirrhosis), clinical situations (excessive use of alcohol or sedatives [e.g., benzodiazepines]; abrupt withdrawal from alcohol or other sedatives; addiction to opiates, cocaine, or stimulants; use of OTC stimulants and anorectics; diabetes treated with oral hypoglycemics or insulin), and concomitant drugs that lower seizure threshold. (See Specific Drugs under Interactions.)

If patients experience a seizure during therapy, discontinue drug and do not restart.

Neuropsychiatric Effects in Patients Treated for Depression

Neuropsychiatric manifestations, including confusion, delusions, hallucinations, psychosis, disturbances in concentration, and paranoia, reported in patients receiving bupropion in depression trials. In some cases, symptoms diminished with dosage reduction or withdrawal of therapy. Similar types of neuropsychiatric manifestations reported during postmarketing experience in patients receiving the drug for smoking cessation. (See Neuropsychiatric Symptoms and Suicidality in Smoking Cessation Treatment under Cautions.)

Activation of Mania or Psychosis

Possible activation of mania or hypomania in bipolar disorder patients; activation of latent psychosis may occur in susceptible patients.

Bupropion is not FDA-labeled for use in treating bipolar depression. Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.

Hypertension

Hypertension (sometimes severe) has occurred with bupropion therapy either alone or in combination with transdermal nicotine in patients with and without pre-existing hypertension. Safety in patients with recent history of MI or unstable heart disease not established.

Specific Populations

Pregnancy

Category B. Bupropion pregnancy registry at 800-336-2176.

Lactation

Distributed into milk; discontinue nursing or drug.

Pediatric Use

Safety and efficacy not established in children <18 years of age.

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others). However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials.

Carefully consider these findings when assessing potential benefits and risks of bupropion in a child or adolescent for any clinical use. (See Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders in Boxed Warning and also under Cautions.)

Has been used in a limited number of children 7–16 years of age for attention deficit disorder^† without unusual adverse effect.

Geriatric Use

Use with caution; possible decreased clearance. No substantial differences in safety and efficacy relative to younger adults.

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo. (See Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders in Boxed Warning and also under Cautions.)

Hepatic Impairment

Use with extreme caution in patients with severe hepatic cirrhosis and caution in patients with hepatic impairment (e.g., mild to moderate hepatic cirrhosis); reduced frequency and/or dosage and close monitoring for adverse effects required. (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use with caution; active metabolites may accumulate. Monitor closely for adverse effects (e.g., seizures); reduction in dosage and/or frequency may be necessary.

Common Adverse Effects

Agitation, dry mouth, insomnia, headache/migraine, nausea/vomiting, constipation, tremor.

Interactions for buPROPion

Metabolized principally by CYP2B6; may also inhibit CYP2D6 and induce other hepatic microsomal enzymes.

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (altered serum concentrations of bupropion) with drugs that induce or inhibit CYP2B6.

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2D6: potential pharmacokinetic interaction (increased plasma substrate concentrations).

Substrates of hepatic microsomal enzymes: potential pharmacokinetic interaction (altered substrate metabolism).

Smoking Cessation

Smoking may induce enzymes and increase metabolism of some drugs. Therefore, cessation of smoking (with or without adjunctive use of bupropion) may result in decreased enzyme induction and altered metabolism of some drugs (e.g., theophylline, warfarin); consider dosage adjustment.

Specific Drugs

buPROPion Pharmacokinetics

Absorption

Bioavailability

Well-absorbed from the GI tract following oral administration. Peak plasma concentrations usually occur within 2, 3, or 5 hours after oral administration of conventional or extended-release tablets of Wellbutrin SR or Wellbutrin XL, respectively.

At steady state, conventional and extended-release tablets (Wellbutrin SR, Wellbutrin XL) are essentially bioequivalent.

Food

Food does not appear to substantially affect the peak plasma concentration or extent of absorption achieved with extended-release tablets.

Distribution

Extent

Bupropion and its metabolites are distributed into milk.

Plasma Protein Binding

≥80% bound to human albumin.

Elimination

Metabolism

Extensively metabolized in the liver to 3 active metabolites: hydroxybupropion (principally by CYP2B6), threohydrobupropion, and erythrohydrobupropion.

Elimination Route

Excreted in urine (87%) and feces (10%), principally as metabolites.

Half-life

The half-life in the terminal phase (t_½β) averages about 14 hours following single doses; with multiple dosing, t_½β reportedly averages 21 hours.

Special Populations

Hepatic impairment can decrease elimination of the drug.

Renal impairment may decrease elimination of major metabolites.

Stability

Storage

Oral

Conventional Tablets

15–25°C; protect from light and moisture.

Extended-release Tablets

Extended-release, film-coated tablets (e.g., Wellbutrin SR, Zyban): tight, light-resistant containers at 20–25°C.

Extended-release tablets (Wellbutrin XL): tight, light-resistant containers at 25°C (may be exposed to temperatures ranging from 15–30°C).

Actions

• Chemically unrelated to tricyclic, tetracyclic, or other currently available antidepressants (e.g., SSRIs); also chemically unrelated to nicotine or other agents currently used in treatment of nicotine dependence.

• Mechanism of antidepressant action is unclear; noradrenergic pathways appear to be principally involved.

• Mechanism of action as an adjunct in the cessation of smoking is unclear; noradrenergic and/or dopaminergic effects presumably are involved.

• Produces less frequent anticholinergic effects, cardiovascular effects, antihistaminic effects, and weight gain compared with tricyclic antidepressants at usual dosages.

Advice to Patients

• Importance of providing copy of written patient information (medication guide) each time bupropion is dispensed.

• Risk of suicidality with antidepressants; importance of patients, families, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment. Advise patients to read the medication guide explaining risks of suicidality before starting bupropion and each time the prescription is refilled.

• Risk of serious neuropsychiatric symptoms, including changes in mood (e.g., depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, and panic as well as suicidal ideation, suicide attempt, and completed suicide, when used for smoking cessation. Advise patients to read the medication guide explaining the risk of such symptoms before starting bupropion and each time the prescription is refilled.

• Importance of advising patients and caregivers that patients using bupropion for smoking cessation should stop drug and immediately contact clinician if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior.

• Importance of advising patients that it usually takes several weeks of antidepressant therapy before they will start to feel better. Advise patients not to stop taking the drug if a response is not evident right away.

• Importance of avoiding concurrent therapy with preparations containing bupropion for use as an adjunct in smoking cessation (e.g., Zyban) and preparations used for treatment of major depressive disorder or seasonal affective disorder (e.g., various Wellbutrin formulations and generic formulations).

• Importance of avoiding some activities (e.g., operating machinery, driving a motor vehicle) until the effects on the individual are known.

• Importance of minimizing or avoiding consumption of alcohol; use of alcohol or abrupt cessation of use may alter the seizure threshold.

• Risk of seizures, particularly in patients with certain medical problems, those taking certain drugs concomitantly, and those receiving higher dosages (see Seizures under Cautions). Advise patients to stop taking the drug and immediately notify their clinician if they have a seizure.

• Risk of anaphylactoid and other sensitivity reactions. Advise patients to stop taking bupropion and notify their clinician immediately if they develop signs of a severe allergic reaction (e.g., rash, itching, hives, fever, swollen lymph glands, painful sores in mouth or around eyes, swelling of lips or tongue, chest pain, difficulty breathing).

• Risk of high blood pressure, which can be severe. Risk may be higher during concurrent use of nicotine replacement therapy (e.g., nicotine patch) for smoking cessation.

• Importance of informing patients that the shell of the extended-release tablet (Wellbutrin XL) does not dissolve and may be passed in the stool.

• Importance of not crushing or chewing extended-release tablets.

• Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.

• Importance of women notifying clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• How long does it take Wellbutrin XL/SR (bupropion) to work?
• Does naltrexone cause weight gain?

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