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buPROPion (Monograph)

Brand names: Aplenzin, Forfivo XL, Wellbutrin
Drug class: Antidepressants, Miscellaneous

Medically reviewed by Drugs.com on Sep 24, 2023. Written by ASHP.

Warning

    Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders

  • Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (18–24 years of age).1 142 143 161 162 168 226 227

  • In short-term clinical trials, risk of suicidality was not increased in adults >24 years of age and apparently was reduced in adults ≥65 years of age with antidepressant therapy compared with placebo.1 161 162 226 227

  • Appropriately monitor and closely observe all patients who are started on bupropion therapy for clinical worsening, suicidality, or unusual changes in behavior; advise family members and/or caregivers of the need for close observation and communication with the clinician.1 142 143 162 161 167 168 226 227

Introduction

Antidepressant and smoking deterrent; aminoketone derivative.1 43 142 143 168 226 227

Uses for buPROPion

Major Depressive Disorder

Treatment of major depressive disorder as defined by the Diagnostic and Statistical Manual (DSM).1 127 128 129 131 132 142 168 179 180 226 227

May be useful (alone or in combination with other antidepressants) in patients with refractory depression.179 180

Recommended as an option for first-line pharmacologic therapy for most patients with major depressive disorder according to clinical guidelines from the American Psychiatric Association (APA).160

Seasonal Affective Disorder

Extended-release tablets (Wellbutrin XL, Aplenzin) used for prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD).168 169 170 171 227

Smoking Cessation

Extended-release (SR) 150-mg tablets used as an adjunct in the cessation of smoking (alone or in combination with nicotine replacement therapy).143 145 146 147 152

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.152

Depression Associated with Bipolar Disorder

Treatment of patients with bipolar depression† [off-label] (bipolar disorder, depressive episode).2 77 78 85 86 102 154

APA considers bupropion one of several second-line agents for use when first-line agents are ineffective or not tolerated.154

Attention Deficit Hyperactivity Disorder (ADHD)

Used in a limited number of children2 44 79 80 134 156 157 158 and adults in the management of ADHD† [off-label].2 44 76 126 228

Panic Disorder

Ineffective in the treatment of panic disorder and concomitant phobic disorder† [off-label],2 44 99 134 but may improve symptoms of panic and depression in patients with major depression who have superimposed panic symptoms.44

buPROPion Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Administration

Oral Administration

Administer orally with or without food.1 142 143 168 226 227

Conventional Bupropion Hydrochloride Tablets

Initially, administer orally twice daily in the morning and evening, then increase to 3 times daily, with ≥6 hours separating doses.1 23 24 141

Dosages ≥300 mg should be administered as divided doses ≤150 mg per dose.1

Avoid bedtime administration of evening dose to decrease incidence of insomnia.1

Do not chew, divide, or crush tablets; swallow tablets whole.1

Extended-release Tablets

Sustained-release (SR), film-coated bupropion hydrochloride tablets (e.g., Wellbutrin SR): Initially, administer orally once daily in the morning, then increase to twice daily, in the morning and evening.142 Dosages >150 mg should be administered as divided doses twice daily, with ≥8 hours separating the doses.142 Avoid bedtime administration of evening dose to decrease incidence of insomnia.142

Extended-release (SR) bupropion hydrochloride tablets: Administer orally once daily for the first 3 days, then usually increase to twice daily administration with ≥8 hours separating the doses.143 Avoid bedtime administration of evening dose to decrease incidence of insomnia.143

Extended-release bupropion hydrobromide (Aplenzin) or bupropion hydrochloride (Wellbutrin XL) tablets: Administer orally once daily in the morning.168 227

Extended-release bupropion hydrochloride 450-mg film-coated tablets (Forfivo XL): Administer orally once daily.226 If insomnia occurs, avoid administration close to bedtime.226

Do not chew, divide, or crush extended-release tablets; tablets should be swallowed whole.142 143 168 226 227

The shell of some extended-release tablets (e.g., Aplenzin, Wellbutrin XL) does not dissolve and may be passed in the stool.168 227

Dosage

Available as bupropion hydrochloride or bupropion hydrobromide; dosage expressed in terms of the salt.1 142 143 168 226 227

Bupropion hydrobromide doses of 174, 348, or 522 mg are equivalent to bupropion hydrochloride doses of 150, 300, or 450 mg, respectively.227

Pediatric Patients

ADHD† [off-label]
Bupropion Hydrochloride
Oral

Children weighing ≥20 kg: Initially, 1 mg/kg daily in 2–3 divided doses.156 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.156

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).157

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.158

Adults

Major Depression

Increase bupropion dosage gradually; avoid exceeding recommended maximum individual doses or daily dosages to minimize risk of seizures.1 142 168 227

Optimum duration of treatment not established; however, acute depressive episodes thought to require several months or longer of sustained antidepressant therapy.1 142 168 226 227 Some clinicians recommend that long-term antidepressant therapy be considered in certain patients at risk for recurrence of depressive episodes (e.g., those with highly recurrent unipolar depression).160

Unknown whether dosage required to induce remission is identical to dosage needed to maintain and/or sustain euthymia.1 142 168 226 227

Antidepressant efficacy of bupropion hydrochloride extended-release, film-coated tablets (Wellbutrin SR) shown to be maintained for periods of up to 44 weeks in patients receiving 150 mg twice daily.142

Efficacy of bupropion hydrochloride conventional tablets beyond 6 weeks not established systematically in controlled studies.1

Periodically reevaluate usefulness and appropriate dosage of drug in patients receiving prolonged therapy with conventional or extended-release tablets.1 142 168 226 227

Therapy with Conventional Bupropion Hydrochloride Tablets
Oral

Initially, 100 mg twice daily.1 Alternatively, dosage may be initiated at 75 mg 3 times daily.23 24 141

To minimize risk of seizures, do not increase dosage by >100 mg daily every 3 days.1 23 24

If clinical improvement not apparent after >3 days, may increase to 100 mg 3 times daily.1 23 24 141 142

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 a maximum of 150 mg 3 times daily.1

Therapy with Extended-release Bupropion Hydrochloride Tablets
Oral

Extended-release, film-coated tablets (e.g., Wellbutrin SR): Initially, 150 mg once daily in the morning.142 If tolerated, may increase to target dosage of 150 mg twice daily (with ≥8 hours between doses) as early as fourth day of therapy.142 Dosages >300 mg daily should not be considered until completion of several weeks of therapy; then, if no apparent improvement, may increase dosage to maximum of 200 mg twice daily (with ≥8 hours between doses).142

Extended-release tablets (Wellbutrin XL): Initially, 150 mg once daily.168 If tolerated, may increase to target dosage of 300 mg once daily after 4 days of therapy.168

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.168

Extended-release 450-mg tablets (Forfivo XL) in patients who have received bupropion hydrochloride 300 mg daily for ≥2 weeks and require a dosage of 450 mg daily, or in patients currently receiving bupropion hydrochloride 450 mg daily: 450 mg once daily.226

When discontinuing therapy with Forfivo XL, use another bupropion formulation to taper the dose prior to discontinuance of bupropion.226

Therapy with Extended-release Bupropion Hydrobromide Tablets
Oral

Extended-release tablets (e.g., Aplenzin): Initially, 174 mg once daily in the morning.227 After 4 days of dosing, may increase to target dosage of 348 mg once daily in the morning.227

When discontinuing therapy in patients receiving 348 mg once daily, taper dosage to 174 mg once daily prior to discontinuance.227

Seasonal Affective Disorder
Therapy with Extended-release Bupropion Hydrochloride 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.168 169 Individualize timing of initiation and duration of therapy based on patient’s historical pattern of seasonal depressive episodes.168

Initially, 150 mg once daily in the morning.168 If tolerated, increase dosage after 7 days to target dosage of 300 mg once daily.168

For patients receiving 300 mg once daily during the autumn-winter period, taper dosage to 150 mg once daily prior to discontinuance.168

Therapy with Extended-release Bupropion Hydrobromide Tablets
Oral

Extended-release tablets (Aplenzin): Initiate therapy in autumn prior to onset of depressive symptoms; continue treatment through the winter and taper and discontinue in early spring.227 Individualize timing of initiation and duration of therapy based on patient’s historic pattern of seasonal depressive episodes.227

Initially, 174 mg once daily.227 After 7 days of dosing, may increase to target dose of 348 mg once daily in the morning.227

For patients receiving 348 mg once daily during the autumn-winter period, taper dosage to 174 mg once daily prior to discontinuance.227

Smoking Cessation
Therapy with Extended-release (SR) Bupropion Hydrochloride Tablets
Oral

Initially, 150 mg daily for the first 3 days of therapy.143 145 Initiate 1–2 weeks prior to discontinuance of cigarette smoking.143 145

Maintenance, 150 mg twice daily (with ≥8 hours between doses).143 145 Continue therapy for 7–12 weeks; evaluate need for prolonged therapy after that period based on individual patient assessment.143

Cessation of smoking is unlikely in patients who do not show substantial progress toward abstinence after 7 weeks of therapy, so such therapy generally should be discontinued at that time in these patients.143

Combination Therapy with Extended-release Bupropion Hydrochloride Tablets and Transdermal Nicotine Patches
Oral

Initially, 150 mg daily, and after 3 days increase to 150 mg twice daily (with ≥8 hours between doses) while still smoking.143

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.143

Taper transdermal nicotine to 14, then to 7 mg/24 hours during the eighth and ninth weeks of therapy, respectively.143

Depression Associated With Bipolar Disorder† [off-label]
Bupropion Hydrochloride
Oral

Dosages generally range from 75–400 mg in conjunction with a mood-stabilizing agent (e.g., carbamazepine, lithium, valproate).2

ADHD†
Therapy with Conventional Bupropion Hydrochloride Tablets
Oral

Initially, 150 mg daily.2 May be titrated up to 450 mg daily.2

Therapy with Extended-release Bupropion Hydrochloride Tablets
Oral

150–450 mg daily.228

Prescribing Limits

Adults

Major Depression
Oral

Conventional bupropion hydrochloride tablets: Maximum 450 mg daily (not >150 mg per dose).1

Extended-release, film-coated bupropion hydrochloride tablets (e.g., Wellbutrin SR): Maximum 400 mg daily (not >200 mg per dose).142

Extended-release bupropion hydrochloride tablets (Wellbutrin XL): Maximum 300 mg daily.168

Extended-release, 450-mg bupropion hydrochloride tablets (Forfivo XL): Maximum 450 mg daily.226

Extended-release bupropion hydrobromide tablets (Aplenzin): Maximum 522 mg daily.227

Seasonal Affective Disorder
Oral

Extended-release bupropion hydrochloride tablets (e.g., Wellbutrin XL): Dosages >300 mg daily not studied.168

Smoking Cessation
Oral

Extended-release (SR) bupropion hydrochloride tablets: 300 mg daily (not >150 mg per dose).143

Special Populations

Hepatic Impairment

Maximum Dosage for Major Depression and Seasonal Affective Disorder in Moderate to Severe Hepatic Impairment (Child-Pugh score: 7–15)1142168

Dosage Form

Maximum Dosage

Conventional bupropion hydrochloride tablets

75 mg once daily1

Extended-release, film-coated bupropion hydrochloride tablets (e.g., Wellbutrin SR)

100 mg once daily or 150 mg every other day142

Extended-release bupropion hydrochloride tablets (Wellbutrin XL)

150 mg every other day168

Extended-release bupropion hydrobromide tablets (Aplenzin)

174 mg every other day227

Smoking cessation in patients with severe hepatic cirrhosis: Maximum 150 mg every other day as extended-release (SR) tablets .143

Major depression, seasonal affective disorder, or smoking cessation in patients with mild hepatic impairment (Child-Pugh score: 5–6): Reduce dosage and/or frequency of administration as required.1 142 143 168 227

Bupropion hydrochloride extended-release, 450-mg tablets (Forfivo XL) are not recommended for use in patients with hepatic impairment.226

Renal Impairment

Active metabolites may accumulate; reduce dosage and/or frequency of administration as required.1 142 143 168 177 227

Smoking cessation in patients undergoing hemodialysis: Some clinicians recommend a dosage of 150 mg every 3 days as extended-release, film-coated bupropion hydrochloride tablets.177

Bupropion hydrochloride extended-release, 450-mg tablets (Forfivo XL) are not recommended for use in patients with renal impairment.226

Detailed Bupropion dosage information

Cautions for buPROPion

Contraindications

Warnings/Precautions

Warnings

Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults

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.1 142 143 161 162 167 168 181 226 227 Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.1 142 143 161 162 167 168 226 227

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.1 142 143 161 162 167 168 226 227

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.1 142 143 161 167 168 226 227 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.1 142 143 161 162 167 168 226 227

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.1 142 143 161 168 226 227

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.1 142 143 161 168 226 227

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid/anaphylactic reactions (e.g., pruritus, urticaria, angioedema, dyspnea) reported; may require medical treatment.1 142 143 168 226 227 Postmarketing reports include erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock.1 142 143 168 226 227

Possible arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity.1 142 143 168 226 227

Advise patients to discontinue bupropion and contact their clinician if symptoms of a possible hypersensitivity reaction occur.1 142 143 168 226 227

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.1 142 143 168 186 187 226 227

Additional analyses and studies, including a large randomized controlled study in >8000 patients, indicate that risk is lower than previously thought and comparable to nicotine replacement therapy or placebo.224 225 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.224

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.224

Monitor patients for neuropsychiatric symptoms or for worsening of preexisting psychiatric conditions.1 142 143 168 226 227 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.1 142 143 168 226 227 Provide ongoing monitoring and supportive care until symptoms resolve.1 142 143 168 186 226 227

Seizures

Dose-related increase in risk of seizures reported;1 6 19 20 24 52 142 143 168 226 227 increase dose gradually and avoid exceeding recommended daily and single doses.1 142 143 168 226 227 Do not exceed a total daily dosage of 450 mg (as 150 mg 3 times daily) of bupropion hydrochloride as conventional tablets;1 400 mg daily (as 200 mg twice daily) of bupropion hydrochloride as extended-release, film-coated tablets (e.g., Wellbutrin SR);142 300 mg daily (as 150 mg twice daily) of bupropion hydrochloride as extended-release (SR) tablets for smoking cessation;143 300 mg once daily of bupropion hydrochloride as extended-release tablets (e.g., Wellbutrin XL);168 450 mg once daily of bupropion hydrochloride as extended-release, 450-mg tablets (Forfivo XL);226 or 522 mg once daily of bupropion hydrobromide as extended-release tablets (Aplenzin).227

Drug is contraindicated in patients with a seizure disorder, anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.1 142 143 168 226 227

Risk factors also include patient-related factors (e.g., history of severe head trauma, arteriovenous malformation, CNS tumor, CNS infection, severe stroke), clinical situations (excessive use of alcohol, benzodiazepines, sedative hypnotic agents, or opiates; use of anorectics; use of illicit drugs [e.g., cocaine]; abuse or misuse of prescription drugs [e.g., CNS stimulants]; metabolic disorders [e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia]; diabetes treated with oral hypoglycemics or insulin), and concomitant drugs that lower seizure threshold (e.g., other bupropion-containing drugs, antipsychotics, tricyclic antidepressants, theophylline, systemic corticosteroids).1 8 142 143 168 226 227

If patients experience a seizure during therapy, discontinue drug and do not restart.1 142 143 168 226 227

Hypertension

Hypertension (sometimes severe) has occurred with bupropion therapy either alone or in combination with transdermal nicotine in patients with and without preexisting hypertension.1 142 143 168 226 227 Risk of hypertension is increased with concomitant use of MAO inhibitors (contraindicated) or other dopaminergic or noradrenergic drugs; also increased with concomitant transdermal nicotine therapy.1 142 143 168 226 227

Safety in patients with recent history of MI or unstable heart disease not established.1 142 143 168 226 227

Assess BP before initiating bupropion and monitor periodically during therapy, especially in patients receiving concomitant nicotine replacement therapy.1 142 143 168 226 227

Activation of Mania or Hypomania

Possible precipitation of manic, mixed, or hypomanic manic episodes; risk appears increased in patients with bipolar disorder or who have risk factors for bipolar disorder.1 142 143 168 226 227

Bupropion is not FDA-labeled for use in treating bipolar depression.1 142 143 168 226 227 Screen for history of bipolar disorder and risk factors for bipolar disorder (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.1 142 161 168 226 227

Psychosis and Other 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.1 142 143 168 226 227 Some of these patients had a diagnosis of bipolar disorder.1 142 143 168 226 227 In some cases, symptoms diminished with dosage reduction or withdrawal of therapy.1 142 143 168 226 227 Similar types of neuropsychiatric manifestations reported during postmarketing experience in patients receiving the drug for smoking cessation.143

Advise patients to contact a clinician if adverse neuropsychiatric effects occur.1 142 143 Discontinue bupropion extended-release tablets (e.g., Wellbutrin XL, Forfivo XL, Aplenzin) if such reactions occur.168 226 227

Angle-closure Glaucoma

Pupillary dilation (mydriasis) occurs with many antidepressants, including bupropion, and may trigger an acute attack of angle-closure glaucoma (narrow-angle glaucoma) in patients with anatomically narrow angles who do not have a patent iridectomy.1 142 143 168 226 227

Laboratory Test Interferences

False-positive results for urine immunoassay screening tests for amphetamines reported in patients receiving bupropion and following discontinuance of drug.1 142 143 168 226 227 Confirmatory tests (e.g., gas chromatography/mass spectrometry) can distinguish bupropion from amphetamines.1 142 143 168 226 227

Specific Populations

Pregnancy

Data from epidemiologic studies have not shown an overall increased risk for congenital malformations with bupropion.1 142 168 226 227 International bupropion pregnancy registry was not designed or powered to evaluate specific defects; however, possible increase in cardiac malformations identified.1 142 168 226 227

National Pregnancy Registry for Antidepressants at 844-405-6185 or [Web].1 142 168 226 227

Consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum.1 142 168 226 227

Encourage pregnant smokers to attempt cessation using educational and behavioral interventions before using drug approaches.143 Use bupropion extended-release (SR) tablets during pregnancy only if potential benefit justifies potential risk to the fetus.143

Lactation

Distributed into milk.1 2 64 142 143 168 226 227 Effects of bupropion or its metabolites on milk production not known.1 142 168 226 227

Limited data from postmarketing reports of bupropion use in nursing women have not identified a clear association of adverse reactions in the breast-fed infant.1 142 168 226 227 Postmarketing reports of seizures in breast-fed infants; however, causal relationship not established.1 142 168 226 227

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 142 143 168 226 227

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).1 142 143 161 162 168 226 227 However, a later 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.181 No suicides occurred in these pediatric trials.1 142 143 161 162 168 181 226 227

Carefully consider these findings when assessing potential benefits and risks of bupropion in a child or adolescent for any clinical use.161 162 167 168 181 226 227

Has been used in a limited number of children 7–16 years of age for attention deficit disorder† without unusual adverse effect.2 44 79 80 134 158

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults; however, possibility of increased sensitivity to drug in some older patients cannot be ruled out.1 2 142 143 168 226 227

Consider increased possibility of impaired renal function, which may increase risk of adverse effects, when selecting dosage; may be useful to monitor renal function.1 142 143 168 226 227

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.1 142 143 161 162 168 226 227

Hepatic Impairment

Reduced dosage required in patients with severe hepatic impairment (Child-Pugh score: 7–15).1 142 143 168 227 In patients with mild hepatic impairment (Child-Pugh score: 5–6), consider reduced frequency and/or dosage.1 142 143 168 227

Use of bupropion hydrochloride extended-release, 450-mg tablets (Forfivo XL) not recommended in patients with hepatic impairment.226

Renal Impairment

Use with caution; parent drug and active metabolites may accumulate.1 142 143 168 177 227 Monitor closely for adverse effects that could indicate high bupropion or metabolite exposures; reduction in dosage and/or frequency may be necessary.1 142 143 168 177 227

Use of bupropion hydrochloride extended-release, 450-mg tablets (Forfivo XL) not recommended in patients with renal impairment.226

Common Adverse Effects

Common adverse effects (≥5%) in patients receiving conventional bupropion hydrochloride tablets: Agitation, dry mouth, constipation, headache/migraine, nausea/vomiting, dizziness, excessive sweating, tremor, insomnia, blurred vision, tachycardia, confusion, rash, hostility, cardiac arrhythmias, auditory disturbance.1

Common adverse effects (≥5%) in patients receiving bupropion hydrochloride extended-release, film-coated tablets (e.g., Wellbutrin SR): Headache, dry mouth, nausea, insomnia, dizziness, pharyngitis, constipation, agitation, anxiety, abdominal pain, tinnitus, tremor, palpitation, myalgia, sweating, rash, anorexia.142

Common adverse effects (≥5%) in patients receiving bupropion hydrochloride extended-release (SR) tablets for smoking cessation: Insomnia, rhinitis, dry mouth, dizziness, nervous disturbance, anxiety, nausea, constipation, arthralgia.143

Common adverse effects (≥5%) in patients receiving bupropion hydrochloride extended-release tablets (e.g., Wellbutrin XL, Forfivo XL ): Dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency, rash.168 226

Common adverse effects (≥5%) in patients receiving bupropion hydrobromide extended-release tablets (e.g., Aplenzin) include dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency, rash.227

Drug Interactions

Metabolized to hydroxybupropion, principally by CYP2B6; CYP isoenzymes not involved in the formation of other bupropion metabolites.1 142 143 168 226 227

Bupropion and its metabolites inhibit CYP2D6.1 142 143 168 226 227

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (altered serum concentrations of bupropion) with drugs that induce or inhibit CYP2B6.1 142 143 168 226 227

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2D6: Potential pharmacokinetic interaction (increased plasma substrate concentrations).1 142 143 168 226 227 Dosage reduction of the CYP2D6 substrate may be necessary, particularly for drugs with a narrow therapeutic index.1 142 143 168 226 227

Prodrugs dependent on CYP2D6 for activation: Possible reduced clinical efficacy of the prodrug.1 142 143 168 226 227 An increase in dosage of the prodrug may be necessary.1 142 143 168 226 227

Smoking Cessation

Smoking may induce enzymes and increase metabolism of some drugs.149 150 151 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, insulin); consider dosage adjustment.143

Specific Drugs

Drug

Interaction

Comments

Alcohol

Possible neuropsychiatric effects or reduced alcohol tolerance1 142 143 168 226 227

Minimize or avoid alcohol consumption1 142 143 168 226 227

Amantadine

Potential increased incidence of adverse CNS effects (e.g., restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, dizziness)1 2 44 55 142 143 168 226 227

Use concomitantly with caution1 142 143 168 226 227

Antiarrhythmic agents, class 1C (e.g., flecainide, propafenone)

Possible decreased metabolism of antiarrhythmic agent1 142 143 144 168 226 227

Use with caution;144 consider dosage reduction of antiarrhythmic agent1 142 143 168 226 227

Antidepressants

Possible lowering of seizure threshold; increased risk of seizures1 142 143 168 226 227

Use with extreme caution; initiate therapy with lower dosages of bupropion and increase gradually1 142 143 168 226 227

Antidepressants, SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline)

Possible decreased metabolism of SSRI1 142 143 144 168 226 227

Possible decreased metabolism of bupropion1 142 143 226 227 168

Use with caution;144 168 consider dosage reduction of SSRI1 142 143 168 226 227

Antidepressants, tricyclic (TCAs) (e.g., desipramine, imipramine, nortriptyline)

Possible decreased TCA metabolism1 142 143 144 168 226 227

Use with caution;144 168 consider dosage reduction of TCA1 142 143 168 226 227

Antipsychotic agents (e.g., haloperidol, risperidone, thioridazine)

Possible lowering of seizure threshold; increased risk of seizures1 142 143 168 226 227

Possible decreased metabolism of antipsychotic1 142 143 144 168 226 227

Use with extreme caution; initiate therapy with lower dosages of bupropion and increase gradually1 142 143 168 226 227

Use with caution;144 consider dosage reduction of antipsychotic agent1 142 143 168 226 227

β-Adrenergic blocking agents (e.g., metoprolol)

Possible decreased metabolism of β-blocker1 142 143 144 168 226 227

Use with caution;144 consider dosage reduction of β-blocker1 142 143 168 226 227

Benzodiazepines

Increased risk of seizures with excessive use or abrupt discontinuance1 142 143

Use with extreme caution; initiate therapy with lower dosages of bupropion and increase gradually1 142 143

Carbamazepine

Possible increased metabolism of bupropion1 138 142 143 168 226 227

Increase in bupropion dosage may be necessary; do not exceed maximum recommended bupropion dosage1 142 143 168 226 227

Cimetidine

Possible decreased metabolism of bupropion1 138 142 143 168 226 227

Use with caution138

Corticosteroids (systemic)

Possible lowering of seizure threshold; increased risk of seizures1 142 143 168 226 227

Use with extreme caution; initiate therapy with lower dosages and increase gradually1 142 143 168 226 227

Digoxin

Possible decreased digoxin concentrations1 142 143

Monitor plasma digoxin concentrations1 142 143

Efavirenz

Possible decreased bupropion exposure; hydroxybupropion exposure unchanged but peak concentration increased1 142 143 168 173 226 227

Increase in bupropion dosage may be necessary; do not exceed maximum recommended bupropion dosage1 142 143 168 226 227

Levodopa

Potential increased incidence of adverse CNS effects (e.g., restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, dizziness)1 2 44 55 142 143 168 226 227

Use concomitantly with caution1 142 143 168 226 227

Lopinavir

Possible decreased bupropion and hydroxybupropion exposure1 142 143 168 226 227

Increase in bupropion dosage may be necessary; do not exceed maximum recommended dosage1 142 143 168 226 227

MAO inhibitors (e.g., phenelzine)

Possible enhanced acute toxicity of bupropion; increased risk of hypertensive reactions1 2 142 143 168 226 227

Concomitant use is contraindicated; ≥14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with bupropion1 142 143 168 226 227 or between discontinuation of bupropion and initiation of an MAO inhibitor1 142 143 168 226 227

MAO inhibitors, reversible (e.g., linezolid, IV methylene blue)

Possible increased risk of hypertensive reactions1 142 143 168 226 227

Do not initiate reversible MAO inhibitors in patients receiving bupropion1 142 143 168 226 227

If urgent treatment with a reversible MAO inhibitor is necessary (alternatives not available and possible benefits outweigh risks), discontinue bupropion prior to administering reversible MAO inhibitor; then, monitor patient for 2 weeks or until 24 hours after last dose of reversible MAO inhibitor; may resume bupropion 24 hours after last dose of reversible MAO inhibitor1 142 143 168 226 227

Nelfinavir

Possible decreased metabolism of bupropion1 142 143 168 173 168 226 227

Nicotine

Possible increased risk of hypertension143

Monitor BP143

Phenobarbital

Possible increased metabolism of bupropion1 138 142 143 168 226 227

Increase in bupropion dosage may be necessary; do not exceed maximum recommended dosage1 142 143 168 226 227

Phenytoin

Possible increased metabolism of bupropion1 138 142 143 168 226 227

Increase in bupropion dosage may be necessary; do not exceed maximum recommended dosage1 142 143 168 226 227

Platelet-aggregation inhibitors (e.g., clopidogrel, prasugrel, ticlopidine)

Potential pharmacokinetic interaction (may increase bupropion exposure but decrease hydroxybupropion exposure)1 142 143 168 226 227

Adjust bupropion dosage if necessary based on clinical response1 142 143 168 226 227

Ritonavir

Possible decreased bupropion and hydroxybupropion exposure1 142 143 168 173 226 227

Increase in bupropion dosage may be necessary; do not exceed maximum recommended dosage1 142 143 168 226 227

Tamoxifen

Possible reduced efficacy of tamoxifen1 142 143 168 226 227

Increased dosage of tamoxifen may be necessary1 142 143 168 226 227

Theophylline

Possible lowering of seizure threshold; increased risk of seizures1 142 143 168 226 227

Use with extreme caution; initiate therapy with lower bupropion dosage and increase gradually1 142 143 168 226 227

Venlafaxine

Possible decreased metabolism of venlafaxine1 142 143 168 226 227

Decrease dosage of venlafaxine if necessary1 142 143 168 226 227

Warfarin

Possible altered PT/INR; infrequently associated with hemorrhagic or thrombotic complications1 142 143 168 226 227
Bupropion drug interactions (more detail)

buPROPion Pharmacokinetics

Absorption

Bioavailability

Well-absorbed from the GI tract following oral administration.60 Peak plasma concentrations usually occur within 2, 3, or 5 hours after oral administration of conventional or extended-release bupropion hydrochloride tablets of Wellbutrin SR or Wellbutrin XL, respectively.1 59 61 90 130 142 168 Peak plasma concentrations occur within approximately 5 or 12 hours under fasted or fed conditions, respectively, after oral administration of extended-release, 450-mg bupropion hydrochloride tablets (Forfivo XL).226 Peak plasma concentrations occur within approximately 5 hours after oral administration of extended-release bupropion hydrobromide tablets (Aplenzin).227

Steady-state plasma concentrations of bupropion achieved within 8 days.1

At steady state, conventional and extended-release tablets (Wellbutrin SR, Wellbutrin XL) are essentially bioequivalent.142 168

Bupropion hydrochloride extended-release, 450-mg tablets (Forfivo XL) and bupropion hydrobromide extended-release tablets (Aplenzin) are bioequivalent to bupropion hydrochloride extended-release tablets (e.g., Wellbutrin XL),226 227 Bupropion hydrobromide doses of 174, 348, or 522 mg are equivalent to bupropion hydrochloride doses of 150, 300, or 450 mg, respectively.227

Food

Food does not appear to substantially affect the peak plasma concentration or extent of absorption achieved with extended-release tablets.142 143 168 226

Distribution

Extent

Bupropion and its metabolites are distributed into milk.1 2 64

Plasma Protein Binding

84% bound to human albumin.1 142 143 168 226 227

Elimination

Metabolism

Extensively metabolized in the liver1 57 60 61 130 142 143 to 3 active metabolites: hydroxybupropion (principally by CYP2B6), threohydrobupropion, and erythrohydrobupropion.1 142 143 168 CYP isoenzymes not involved in the formation of threohydrobupropion and erythrohydrobupropion metabolites.1 142

Elimination Route

Excreted in urine (87%) and feces (10%), principally as metabolites.1 61 130 142 143 168

Half-life

The half-life in the terminal phase (t½β) averages about 14 hours following single doses;57 61 90 130 139 226 with multiple dosing, t½β reportedly averages 21 hours.1 139 142

Special Populations

Hepatic impairment can decrease elimination of bupropion.1 142 143 168

Renal impairment may decrease elimination of major metabolites.1 142 143 168 177

Stability

Storage

Oral

Conventional Bupropion Hydrochloride Tablets

20–25°C in tight container; protect from light and moisture.1

Extended-release Bupropion Hydrochloride Tablets

Extended-release (e.g., Wellbutrin SR): 20–25°C (excursions permitted to 15–30°C); protect from light and moisture.142 143

Extended-release tablets (Wellbutrin XL): 25°C (excursions permitted to 15–30°C).168

Extended-release 450-mg tablets (Forfivo XL): 20–25°C.226

Extended-release Bupropion Hydrobromide Tablets

Extended-release tablets (Aplenzin): 25°C (excursions permitted to 15–30°C).227

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

buPROPion Hydrobromide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

174 mg

Aplenzin

Bausch Health US

348 mg

Aplenzin

Bausch Health US

522 mg

Aplenzin

Bausch Health US

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

buPROPion Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

150 mg*

buPROPion Hydrochloride Extended-release Tablets (SR)

Wellbutrin XL

Bausch Health US

300 mg*

Wellbutrin XL

Bausch Health US

450 mg

Forfivo XL

Almatica Pharma

Tablets, extended-release, film-coated

100 mg*

buPROPion Hydrochloride Extended-release Tablets

Wellbutrin SR

GlaxoSmithKline

150 mg*

buPROPion Hydrochloride Extended-release Tablets

Wellbutrin SR

GlaxoSmithKline

200 mg*

buPROPion Hydrochloride Extended-release Tablets

Wellbutrin SR

GlaxoSmithKline

Tablets, film-coated

75 mg*

buPROPion Hydrochloride Tablets

100 mg*

buPROPion Hydrochloride Tablets

AHFS DI Essentials™. © Copyright 2024, Selected Revisions September 24, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Cipla USA, Inc. Bupropion hydrochloride tablets prescribing information. Warren, NJ; 2023 Mar. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=e4100232-a25d-4468-9057-af7e66205154

2. Burroughs Wellcome Co. Wellbutrin (bupropion HCl) tablets: clinical perspective–a survey of relevant medical information. Research Triangle Park, NC; 1995 Jul.

3. Lineberry CG, Johnston JA, Raymond RN et al. A fixed-dose (300 mg) efficacy study of bupropion and placebo in depressed outpatients. J Clin Psychiatry. 1990; 51:194-9. http://www.ncbi.nlm.nih.gov/pubmed/2110559?dopt=AbstractPlus

4. Kirksey DF, Stern WC. Multicenter private practice evaluation of the safety and efficacy of bupropion in depressed geriatric outpatients. Curr Ther Res. 1984; 35:200-10.

5. Kirksey DF, Harto-Truax N. Private practice evaluation of the safety and efficacy of bupropion in depressed outpatients. J Clin Psychiatry. 1983; 44:143-7. http://www.ncbi.nlm.nih.gov/pubmed/6406446?dopt=AbstractPlus

6. Van Wyck Fleet J, Manberg PJ, Miller LL et al. Overview of clinically significant adverse reactions to bupropion. J Clin Psychiatry. 1983; 44:191-6. http://www.ncbi.nlm.nih.gov/pubmed/6406456?dopt=AbstractPlus

7. Zung WWK. Review of placebo-controlled trials with bupropion. J Clin Psychiatry. 1983; 44:104-14. http://www.ncbi.nlm.nih.gov/pubmed/6406436?dopt=AbstractPlus

8. Hayes PE, Kristoff CA. Adverse reactions to five new antidepressants. Clin Pharm. 1986; 5:471-80. http://www.ncbi.nlm.nih.gov/pubmed/3087684?dopt=AbstractPlus

9. Golden RN, James SP, Sherer MA et al. Psychoses associated with bupropion treatment. Am J Psychiatry. 1985; 142:1459-62. http://www.ncbi.nlm.nih.gov/pubmed/3934991?dopt=AbstractPlus

10. Ames D, Wirshing WC, Szuba MP. Organic mental disorders associated with bupropion in three patients. J Clin Psychiatry. 1992; 53:53-5. http://www.ncbi.nlm.nih.gov/pubmed/1541606?dopt=AbstractPlus

11. Szuba MP, Leuchter AF. Falling backward in two elderly patients taking bupropion. J Clin Psychiatry. 1992; 53:157-9. http://www.ncbi.nlm.nih.gov/pubmed/1592841?dopt=AbstractPlus

12. Strouse TB, Salehmoghaddam S, Spar JE. Acute delirium and parkinsonism in a bupropion-treated liver transplant recipient. J Clin Psychiatry. 1993; 54:489-90. http://www.ncbi.nlm.nih.gov/pubmed/8276742?dopt=AbstractPlus

13. Bittman BJ, Young RC. Mania in an elderly man treated with bupropion. Am J Psychiatry. 1991; 148:541. http://www.ncbi.nlm.nih.gov/pubmed/1900981?dopt=AbstractPlus

14. Zubieta JK, Demitrack MA. Possible bupropion precipitation of mania and a mixed affective state. J Clin Psychopharmacol. 1991; 11:327-8. http://www.ncbi.nlm.nih.gov/pubmed/1765576?dopt=AbstractPlus

15. Fichtner CG, Braun BG. Bupropion-associated mania in a patient with HIV infection. J Clin Psychopharmacol. 1992; 12:366-7. http://www.ncbi.nlm.nih.gov/pubmed/1479060?dopt=AbstractPlus

16. Zubieta JK, Demitrack MA. Bupropion-associated mania in a patient with HIV infection. J Clin Psychopharmacol. 1992; 12:367. http://www.ncbi.nlm.nih.gov/pubmed/1479061?dopt=AbstractPlus

17. Johnston JA, Lineberry CG, Frieden CS. Prevalence of psychosis, delusions, and hallucinations in clinical trials with bupropion. Am J Psychiatry. 1986; 143:1192-3. http://www.ncbi.nlm.nih.gov/pubmed/3092682?dopt=AbstractPlus

18. Golden RN, Rudorfer MV, Potter WZ. Prevalence of psychosis, delusions, and hallucinations in clinical trials with bupropion. Am J Psychiatry. 1986; 143:1193. http://www.ncbi.nlm.nih.gov/pubmed/3752306?dopt=AbstractPlus

19. Bryant SG, Guernsey BG, Ingrim NB. Review of bupropion. Clin Pharm. 1983; 2:525-37. http://www.ncbi.nlm.nih.gov/pubmed/6140095?dopt=AbstractPlus

20. Peck AW, Stern WC, Watkinson C. Incidence of seizures during treatment with tricyclic antidepressant drugs and bupropion. J Clin Psychiatry. 1983; 44:197-201. http://www.ncbi.nlm.nih.gov/pubmed/6406457?dopt=AbstractPlus

21. Rosenstein DL, Nelson JC, Jacobs SC. Seizures associated with antidepressants: a review. J Clin Psychiatry. 1993; 54:289-99. http://www.ncbi.nlm.nih.gov/pubmed/8253696?dopt=AbstractPlus

22. Skowron DM, Stimmel GL. Antidepressants and the risk of seizures. Pharmacotherapy. 1992; 12:18-22. http://www.ncbi.nlm.nih.gov/pubmed/1549533?dopt=AbstractPlus

23. Johnston JA, Lineberry CG, Ascher JA et al. A 102-center prospective study of seizure in association with bupropion. J Clin Psychiatry. 1991; 52:450-6. http://www.ncbi.nlm.nih.gov/pubmed/1744061?dopt=AbstractPlus

24. Davidson J. Seizures and bupropion: a review. J Clin Psychiatry. 1989; 50:256-61. http://www.ncbi.nlm.nih.gov/pubmed/2500425?dopt=AbstractPlus

25. Becker RE, Dufresne RL. Perceptual changes with bupropion, a novel antidepressant. Am J Psychiatry. 1982; 139:1200-1. http://www.ncbi.nlm.nih.gov/pubmed/6810715?dopt=AbstractPlus

26. van Putten T, Shaffer I. Delirium associated with bupropion. J Clin Psychopharmacol. 1990; 10:234. http://www.ncbi.nlm.nih.gov/pubmed/2115897?dopt=AbstractPlus

27. Dager SR, Heritch AJ. A case of bupropion-associated delirium. J Clin Psychiatry. 1990; 51:307-8. http://www.ncbi.nlm.nih.gov/pubmed/2114399?dopt=AbstractPlus

28. Liberzon I, Dequardo JR, Silk KR. Bupropion and delirium. Am J Psychiatry. 1990; 147:1689-90. http://www.ncbi.nlm.nih.gov/pubmed/2123081?dopt=AbstractPlus

29. Harto-Truax N, Stern WC, Miller LL et al. Effects of bupropion on body weight. J Clin Psychiatry. 1983; 44:183-6. http://www.ncbi.nlm.nih.gov/pubmed/6406454?dopt=AbstractPlus

30. Gardner EA. Effects of bupropion on weight in patients intolerant to previous antidepressants. Curr Ther Res. 1984; 35:188-99.

31. Workman EA, Short DD. Bupropion-induced carbohydrate craving and weight gain. Am J Psychiatry. 1992; 149:1407-8. http://www.ncbi.nlm.nih.gov/pubmed/1530081?dopt=AbstractPlus

32. Roose SP, Dalack GW, Glassman AH et al. Cardiovascular effects of bupropion in depressed patients with heart disease. Am J Psychiatry. 1991; 148:512-6. http://www.ncbi.nlm.nih.gov/pubmed/1900980?dopt=AbstractPlus

33. Roose SP, Glassman AH, Giardina EGV et al. Cardiovascular effects of imipramine and bupropion in depressed patients with congestive heart failure. J Clin Psychopharmacol. 1987; 7:247-51. http://www.ncbi.nlm.nih.gov/pubmed/3114333?dopt=AbstractPlus

34. Wenger TL, Stern WC. The cardiovascular profile of bupropion. J Clin Psychiatry. 1983; 44:176-82. http://www.ncbi.nlm.nih.gov/pubmed/6406453?dopt=AbstractPlus

35. Othmer E, Othmer SC, Stern WC et al. Long-term efficacy and safety of bupropion. J Clin Psychiatry. 1983; 44:153-6. http://www.ncbi.nlm.nih.gov/pubmed/6406448?dopt=AbstractPlus

36. Halbreich U, Rojansky N, Bakhai Y et al. Menstrual irregularities associated with bupropion treatment. J Clin Psychiatry. 1991; 52:15-6. http://www.ncbi.nlm.nih.gov/pubmed/1899086?dopt=AbstractPlus

37. Settle EC Jr. Tinnitus related to bupropion treatment. J Clin Psychiatry. 1991; 52:352. http://www.ncbi.nlm.nih.gov/pubmed/1907965?dopt=AbstractPlus

38. Farid FF, Wenger TL, Tsai SY et al. Use of bupropion in patients who exhibit orthostatic hypotension on tricyclic antidepressants. J Clin Psychiatry. 1983; 44:170-3. http://www.ncbi.nlm.nih.gov/pubmed/6406451?dopt=AbstractPlus

39. Horne RL, Ferguson JM, Pope HG Jr. et al. Treatment of bulimia with bupropion: a multicenter controlled trial. J Clin Psychiatry. 1988; 49:262-6. http://www.ncbi.nlm.nih.gov/pubmed/3134343?dopt=AbstractPlus

40. Oslin DW, Duffy K. The rise of serum aminotransferases in a patient treated with bupropion. J Clin Psychopharmacol. 1993; 13:364-5. http://www.ncbi.nlm.nih.gov/pubmed/8227497?dopt=AbstractPlus

41. Goldberg JP. Bupropion dose, seizures, women, and age. J Clin Psychiatry. 1990; 51:388-9. http://www.ncbi.nlm.nih.gov/pubmed/2120202?dopt=AbstractPlus

42. Davidson JRT. Bupropion dose, seizures, women, and age. J Clin Psychiatry. 1990; 51:389. http://www.ncbi.nlm.nih.gov/pubmed/2211556?dopt=AbstractPlus

43. Mehta NB. The chemistry of bupropion. J Clin Psychiatry. 1983; 44:56-9. http://www.ncbi.nlm.nih.gov/pubmed/6406464?dopt=AbstractPlus

44. Settle EC Jr. Bupropion: update 1993. Int Drug Ther Newsl. 1993; 28: 29-36.

45. Chouinard G. Bupropion and amitriptyline in the treatment of depressed patients. J Clin Psychiatry. 1983; 44:121-9. http://www.ncbi.nlm.nih.gov/pubmed/6406440?dopt=AbstractPlus

46. Branconnier RJ, Cole JO, Ghazvinian S et al. Clinical pharmacology of bupropion and imipramine in elderly depressives. J Clin Psychiatry. 1983; 44:130-3. http://www.ncbi.nlm.nih.gov/pubmed/6406441?dopt=AbstractPlus

47. Pitts WM, Fann WE, Halaris AE et al. Bupropion in depression: a tri-center placebo-controlled study. J Clin Psychiatry. 1983; 44:95-100. http://www.ncbi.nlm.nih.gov/pubmed/6406473?dopt=AbstractPlus

48. Fabre LF, Brodie HKH, Garver D et al. A multicenter evaluation of bupropion versus placebo in hospitalized depressed patients. J Clin Psychiatry. 1983; 44:88-94. http://www.ncbi.nlm.nih.gov/pubmed/6406472?dopt=AbstractPlus

49. Merideth CH, Feighner JP. The use of bupropion in hospitalized depressed patients. J Clin Psychiatry. 1983; 44:85-7. http://www.ncbi.nlm.nih.gov/pubmed/6406471?dopt=AbstractPlus

50. Gardner EA. Long-term preventive care in depression: the use of bupropion in patients intolerant of other antidepressants. J Clin Psychiatry. 1983; 44:157-62. http://www.ncbi.nlm.nih.gov/pubmed/6406449?dopt=AbstractPlus

51. Stern WC, Harto-Truax N, Bauer N. Efficacy of bupropion in tricyclic-resistant or intolerant patients. J Clin Psychiatry. 1983; 44:148-52. http://www.ncbi.nlm.nih.gov/pubmed/6406447?dopt=AbstractPlus

52. Cato AE, Cook L, Starbuck R et al. Methodologic approach to adverse events applied to bupropion clinical trials. J Clin Psychiatry. 1983; 44:187-90. http://www.ncbi.nlm.nih.gov/pubmed/6406455?dopt=AbstractPlus

53. Feighner J, Hendrickson G, Miller L et al. Double-blind comparison of doxepin versus bupropion in outpatients with a major depressive disorder. J Clin Psychopharmacol. 1986; 6:27-32. http://www.ncbi.nlm.nih.gov/pubmed/3081600?dopt=AbstractPlus

54. Feighner JP, Gardner EA, Johnston JA et al. Double-blind comparison of bupropion and fluoxetine in depressed outpatients. J Clin Psychiatry. 1991; 52:329-35. http://www.ncbi.nlm.nih.gov/pubmed/1907963?dopt=AbstractPlus

55. Goetz CG, Tanner CM, Klawans HL. Bupropion in Parkinson’s disease. Neurology. 1984; 34:1092-4. http://www.ncbi.nlm.nih.gov/pubmed/6431314?dopt=AbstractPlus

56. Miller L, Griffith J. A comparison of bupropion, dextroamphetamine, and placebo in mixed-substance abusers. Psychopharmacology. 1983; 80:199-205. http://www.ncbi.nlm.nih.gov/pubmed/6412263?dopt=AbstractPlus

57. Findlay JWA, Van Wyck Fleet J, Smith PG et al. Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects. Eur J Clin Pharmacol. 1981; 21:127-35. http://www.ncbi.nlm.nih.gov/pubmed/6804243?dopt=AbstractPlus

58. DeVane CL, Laizure SC, Stewart JT et al. Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease. J Clin Psychopharmacol. 1990; 10:328-32. http://www.ncbi.nlm.nih.gov/pubmed/2124217?dopt=AbstractPlus

59. 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; 38:586-9. http://www.ncbi.nlm.nih.gov/pubmed/3931955?dopt=AbstractPlus

60. Schroeder DH. Metabolism and kinetics of bupropion. J Clin Psychiatry. 1983; 44:79-81. http://www.ncbi.nlm.nih.gov/pubmed/6406469?dopt=AbstractPlus

61. Lai AA, Schroeder DH. Clinical pharmacokinetics of bupropion: a review. J Clin Psychiatry. 1983; 44:82-4. http://www.ncbi.nlm.nih.gov/pubmed/6406470?dopt=AbstractPlus

62. Posner J, Bye A, Dean K et al. The disposition of bupropion and its metabolites in healthy male volunteers after single and multiple doses. Eur J Clin Pharmacol. 1985; 29:97-103. http://www.ncbi.nlm.nih.gov/pubmed/3932079?dopt=AbstractPlus

63. Golden RN, Rudorfer MV, Sherer MA et al. Bupropion in depression: I. Biochemical effects and clinical response. Arch Gen Psychiatry. 1988; 45:139-43. http://www.ncbi.nlm.nih.gov/pubmed/3122698?dopt=AbstractPlus

64. Briggs GG, Samson JH, Ambrose PJ et al. Excretion of bupropion in breast milk. Ann Pharmacother. 1993; 27:431-3. http://www.ncbi.nlm.nih.gov/pubmed/8477117?dopt=AbstractPlus

65. Preskorn SH, Fleck RJ, Schroeder DH. Therapeutic drug monitoring of bupropion. Am J Psychiatry. 1990; 147:1690-1. http://www.ncbi.nlm.nih.gov/pubmed/2123082?dopt=AbstractPlus

66. Goodnick PJ. Blood levels and acute response to bupropion. Am J Psychiatry. 1992; 149:399-400. http://www.ncbi.nlm.nih.gov/pubmed/1536282?dopt=AbstractPlus

67. Golden RN, DeVane CL, Laizure SC. Bupropion in depression: II. The role of metabolites in clinical outcome. Arch Gen Psychiatry. 1988; 45:145-9. http://www.ncbi.nlm.nih.gov/pubmed/3122699?dopt=AbstractPlus

68. Preskorn SH. Antidepressant response and plasma concentrations of bupropion. J Clin Psychiatry. 1983; 44::137-9.

69. Gittelman DK, Kirby MG. A seizure following bupropion overdose. J Clin Psychiatry. 1993; 54:162. http://www.ncbi.nlm.nih.gov/pubmed/8486598?dopt=AbstractPlus

70. Storrow AB. Bupropion overdose and seizure. Am J Emerg Med. 1994; 12:183-4. http://www.ncbi.nlm.nih.gov/pubmed/8161393?dopt=AbstractPlus

71. Spiller HA, Ramoska EA, Krenzelok EP et al. Bupropion overdose: a 3-year multi-center retrospective analysis. Am J Emerg Med. 1994; 12:43-5. http://www.ncbi.nlm.nih.gov/pubmed/8285970?dopt=AbstractPlus

72. Jackson CW, Head LA, Kellner CH. Catatonia associated with bupropion treatment. J Clin Psychiatry. 1992; 53:210. http://www.ncbi.nlm.nih.gov/pubmed/1607350?dopt=AbstractPlus

73. Dilsaver SC, Qamar AB, Del Medico VJ. The efficacy of bupropion in winter depression: results of an open trial. J Clin Psychiatry. 1992; 53:252-5. http://www.ncbi.nlm.nih.gov/pubmed/1639745?dopt=AbstractPlus

74. Goodnick PJ. Bupropion in chronic fatigue syndrome. Am J Psychiatry. 1990; 147:1091. http://www.ncbi.nlm.nih.gov/pubmed/2115748?dopt=AbstractPlus

75. Emmanuel NP, Lydiard RB, Ballenger JC. Treatment of social phobia with bupropion. J Clin Psychopharmacol. 1991; 11:276-7. http://www.ncbi.nlm.nih.gov/pubmed/1918431?dopt=AbstractPlus

76. Wender PH, Reimherr FW. Bupropion treatment of attention-deficit hyperactivity disorder in adults. Am J Psychiatry. 1990; 147:1018-20. http://www.ncbi.nlm.nih.gov/pubmed/2115746?dopt=AbstractPlus

77. Wright G, Galloway L, Kim J et al. Bupropion in the long-term treatment of cyclic mood disorders: mood stabilizing effects. J Clin Psychiatry. 1985; 46:22-5. http://www.ncbi.nlm.nih.gov/pubmed/2856918?dopt=AbstractPlus

78. Haykal RF, Akiskal HS. Bupropion as a promising approach to rapid cycling bipolar II patients. J Clin Psychiatry. 1990; 51:450-5. http://www.ncbi.nlm.nih.gov/pubmed/2121720?dopt=AbstractPlus

79. Barrickman LL, Perry PJ, Allen AJ et al. Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1995; 34:649-57. http://www.ncbi.nlm.nih.gov/pubmed/7775360?dopt=AbstractPlus

80. Bloomingdale LM. Change from Mg-pemoline to bupropion in a 12-year-old boy with attention-deficit hyperactivity disorder. J Clin Psychopharmacol. 1990; 10:382-3. http://www.ncbi.nlm.nih.gov/pubmed/2124222?dopt=AbstractPlus

81. Davidson JRT, France RD. Bupropion in chronic low back pain. J Clin Psychiatry. 1994; 55:362. http://www.ncbi.nlm.nih.gov/pubmed/8071306?dopt=AbstractPlus

82. Margolin A, Kosten T, Petrakis I et al. Bupropion reduces cocaine abuse in methadone-maintained patients. Arch Gen Psychiatry. 1991; 48:87. http://www.ncbi.nlm.nih.gov/pubmed/1898631?dopt=AbstractPlus

83. Hollister LE, Krajewski K, Rustin T et al. Drugs for cocaine dependence: not easy. Arch Gen Psychiatry. 1992; 49:905. http://www.ncbi.nlm.nih.gov/pubmed/1444730?dopt=AbstractPlus

84. Margolin A, Kosten TR, Avants SK. Drugs for cocaine dependence: not easy. Arch Gen Psychiatry. 1992; 49:905-6. http://www.ncbi.nlm.nih.gov/pubmed/1444730?dopt=AbstractPlus

85. Sachs GS, Lafer B, Stoll AL et al. A double-blind trial of bupropion versus desipramine for bipolar depression. J Clin Psychiatry. 1994; 55:391-3. http://www.ncbi.nlm.nih.gov/pubmed/7929019?dopt=AbstractPlus

86. Fogelson DL, Bystritsky A, Pasnau R. Bupropion in the treatment of bipolar disorders: the same old story? J Clin Psychiatry. 1992; 53:443-6. (IDIS 307853)

87. Levenson JL. Priapism associated with bupropion treatment. Am J Psychiatry. 1995; 152:813. http://www.ncbi.nlm.nih.gov/pubmed/7726332?dopt=AbstractPlus

88. Nofzinger EA, Reynolds CF III, Thase ME et al. REM sleep enhancement by bupropion in depressed men. Am J Psychiatry. 1995; 152:274-6. http://www.ncbi.nlm.nih.gov/pubmed/7840365?dopt=AbstractPlus

89. Stoll AL, Mayer PV, Kolbrener M et al. Antidepressant-associated mania: a controlled comparison with spontaneous mania. Am J Psychiatry. 1994; 151:1642-5. http://www.ncbi.nlm.nih.gov/pubmed/7943454?dopt=AbstractPlus

90. Goodnick PJ. Pharmacokinetic optimisation of therapy with newer antidepressants. Clin Pharmacokinet. 1994; 27:307-30. http://www.ncbi.nlm.nih.gov/pubmed/7834966?dopt=AbstractPlus

91. Wenger TL, Cohn JB, Bustrack J. Comparison of the effects of bupropion and amitriptyline on cardiac conduction in depressed patients. J Clin Psychiatry. 1983; 44:174-5. http://www.ncbi.nlm.nih.gov/pubmed/6406452?dopt=AbstractPlus

92. Masco HL, Kiev A, Holloman LC et al. Safety and efficacy of bupropion and nortriptyline in outpatients with depression. Curr Ther Res. 1994; 55:851-63.

93. Weisler RH, Johnston JA, Lineberry CG et al. Comparison of bupropion and trazodone for the treatment of major depression. J Clin Psychopharmacol. 1994; 14:170-9. http://www.ncbi.nlm.nih.gov/pubmed/8027413?dopt=AbstractPlus

94. Figiel GS, Jarvis MR. Electroconvulsive therapy in a depressed patient receiving bupropion. J Clin Psychopharmacol. 1990; 10:376. http://www.ncbi.nlm.nih.gov/pubmed/2124220?dopt=AbstractPlus

95. Kellner CH, Pritchett JT, Jackson CW. Bupropion coadministration with electroconvulsive therapy: two case reports. J Clin Psychopharmacol. 1994; 14:215-6. http://www.ncbi.nlm.nih.gov/pubmed/8027425?dopt=AbstractPlus

96. Michell GF, Mebane AH, Billings CK. Effect of bupropion on chocolate craving. Am J Psychiatry. 1989; 146:119-20. http://www.ncbi.nlm.nih.gov/pubmed/2492163?dopt=AbstractPlus

97. Whiteman PD, Peck AW, Fowle ASE et al. Failure of bupropion to affect prolactin or growth hormone in man. J Clin Psychiatry. 1983; 44:209-10. http://www.ncbi.nlm.nih.gov/pubmed/6406460?dopt=AbstractPlus

98. Novac A. Fluoxetine and bupropion treatment of bipolar disorder, type II, associated with GAD. J Clin Psychiatry. 1992; 53:67. http://www.ncbi.nlm.nih.gov/pubmed/1541607?dopt=AbstractPlus

99. Sheehan DV, Davidson J, Manschreck T et al. Lack of efficacy of a new antidepressant (bupropion) in the treatment of panic disorder with phobias. J Clin Psychopharmacol. 1983; 3:28-31. http://www.ncbi.nlm.nih.gov/pubmed/6403599?dopt=AbstractPlus

100. Laakmann G, Hoffmann N, Hofschuster E. The lack of effect of bupropion HCL (Wellbutrin) on the secretion of growth hormone and prolactin in humans. Life Sci. 1982; 30:1725-32. http://www.ncbi.nlm.nih.gov/pubmed/6124859?dopt=AbstractPlus

101. Whiteman PD, Peck AW, Fowle ASE et al. Bupropion fails to affect plasma prolactin and growth hormone in normal subjects. Br J Clin Pharmacol. 1982; 13:743-5. http://www.ncbi.nlm.nih.gov/pubmed/6805494?dopt=AbstractPlus

102. Shopsin B. Bupropion’s prophylactic efficacy in bipolar affective illness. J Clin Psychiatry. 1983; 44:163-9. http://www.ncbi.nlm.nih.gov/pubmed/6406450?dopt=AbstractPlus

103. Chouinard G, Annable L, Langlois R. Absence of orthostatic hypotension in depressed patients treated with bupropion. Prog Neuropsychopharmacol. 1981; 5:483-90. http://www.ncbi.nlm.nih.gov/pubmed/6803273?dopt=AbstractPlus

104. Rudorfer MV, Manji HK, Potter WZ. Comparative tolerability profiles of the newer versus older antidepressants. Drug Saf. 1994; 10:18-46. http://www.ncbi.nlm.nih.gov/pubmed/8136085?dopt=AbstractPlus

105. Rakatansky H. Chocolate: pleasure or pain? Am J Psychiatry. 1989; 146:1089. Letter.

106. Michell GF, Mebane AH, Billings CK. Chocolate: pleasure or pain? Am J Psychiatry. 1989; 146:1089. Reply.

107. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV™. 4th ed. Washington, DC: American Psychiatric Association; 1994:320-7.

108. Swartz CM. Advancing age may inhibit antidepressant-induced seizure. J Clin Psychiatry. 1993; 54:202. http://www.ncbi.nlm.nih.gov/pubmed/8509355?dopt=AbstractPlus

109. Griffith JD, Carranza J, Griffith C et al. Bupropion: clinical assay for amphetamine-like abuse potential. J Clin Psychiatry. 1983; 44:206-8. http://www.ncbi.nlm.nih.gov/pubmed/6406459?dopt=AbstractPlus

110. Rudorfer MV, Manji HK, Potter WZ. Bupropion, ECT, and dopaminergic overdrive. Am J Psychiatry. 1991; 148:1101-2. http://www.ncbi.nlm.nih.gov/pubmed/1906685?dopt=AbstractPlus

111. Dequardo JR, Liberzon I, Silk KR. Bupropion, ECT, and dopaminergic overdrive. Am J Psychiatry. 1991; 148:1102. http://www.ncbi.nlm.nih.gov/pubmed/1853978?dopt=AbstractPlus

112. Gardner EA, Johnston JA. Bupropion—an antidepressant without sexual pathophysiological action. J Clin Psychopharmacol. 1985; 5:24-9. http://www.ncbi.nlm.nih.gov/pubmed/3919069?dopt=AbstractPlus

113. Fowle ASE, Peck AW, Rogers HJ et al. Failure of bupropion to affect tyramine response in man. J Clin Psychiatry. 1983; 44:211. http://www.ncbi.nlm.nih.gov/pubmed/6406461?dopt=AbstractPlus

114. Fowle ASE, Peck AW, Rogers HJ et al. Failure of bupropion to affect the response to tyramine in man. Br J Clin Pharmacol. 1981; 12:86-8. http://www.ncbi.nlm.nih.gov/pubmed/6788059?dopt=AbstractPlus

115. Cooper BR, Wang CM, Cox RF et al. Evidence that the acute behavioral and electrophysiological effects of bupropion (Wellbutrin) are mediated by a noradrenergic mechanism. Neuropsychopharmacology. 1994; 11:133-41. http://www.ncbi.nlm.nih.gov/pubmed/7840865?dopt=AbstractPlus

116. Manberg PJ, Carter RG. Bupropion in the treatment of psychotic depression: two case reports. J Clin Psychiatry. 1984; 45:230-1. http://www.ncbi.nlm.nih.gov/pubmed/6427198?dopt=AbstractPlus

117. Goode DJ, Manning AA. Comparison of bupropion alone and with haloperidol in schizo-affective disorder, depressed type. J Clin Psychiatry. 1983; 44:253-5. http://www.ncbi.nlm.nih.gov/pubmed/6408068?dopt=AbstractPlus

118. Walker PW, Cole JO, Gardner EA et al. Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion. J Clin Psychiatry. 1993; 54:459-65. http://www.ncbi.nlm.nih.gov/pubmed/8276736?dopt=AbstractPlus

119. Posner J, Bye A, Jeal S et al. Alcohol and bupropion pharmacokinetics in healthy male volunteers. Eur J Clin Pharmacol. 1984; 26:627-30. http://www.ncbi.nlm.nih.gov/pubmed/6432553?dopt=AbstractPlus

120. Hamilton MJ, Bush MS, Peck AW. The effect of bupropion, a new antidepressant drug, and alcohol and their interaction in man. Eur J Clin Pharmacol. 1984; 27:75-80. http://www.ncbi.nlm.nih.gov/pubmed/6436033?dopt=AbstractPlus

121. Nierenberg AA, Adler LA, Peselow E et al. Trazodone for antidepressant-associated insomnia. Am J Psychiatry. 1994; 151:1069-72. http://www.ncbi.nlm.nih.gov/pubmed/8010365?dopt=AbstractPlus

122. Kiev A, Masco HL, Wenger TL et al. The cardiovascular effects of bupropion and nortriptyline in depressed outpatients. Ann Clin Psychiatry. 1994; 6:107-115. http://www.ncbi.nlm.nih.gov/pubmed/7804386?dopt=AbstractPlus

123. Peck AW, Hamilton M. Psychopharmacology of bupropion in normal volunteers. J Clin Psychiatry. 1983; 44:202-5. http://www.ncbi.nlm.nih.gov/pubmed/6406458?dopt=AbstractPlus

124. Hamilton MJ, Bush M, Smith P et al. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982; 14:791-7. http://www.ncbi.nlm.nih.gov/pubmed/6817770?dopt=AbstractPlus

125. Labbate LA, Pollack MH. Treatment of fluoxetine-induced sexual dysfunction with bupropion: a case report. Ann Clin Psychiatry. 1994; 6:13-5. http://www.ncbi.nlm.nih.gov/pubmed/7951639?dopt=AbstractPlus

126. Wilens TE, Biederman J, Spencer TJ et al. Pharmacotherapy of adult attention deficit/hyperactivity disorder: a review. J Clin Psychopharmacol. 1995; 15:270-9. http://www.ncbi.nlm.nih.gov/pubmed/7593710?dopt=AbstractPlus

127. Whitefield SG. Comment on letter to the editors: a systematic approach to the classification and pharmacotherapy of nonpsychotic major depression and dysthymia. J Clin Psychopharmacol. 1994; 14:218-9. http://www.ncbi.nlm.nih.gov/pubmed/8027427?dopt=AbstractPlus

128. Osser DN. Reply: a systematic approach to the classification and pharmacotherapy of nonpsychotic major depression and dysthymia. J Clin Psychopharmacol. 1994; 14:219.

129. Osser DN. A systematic approach to the classification and pharmacotherapy of nonpsychotic major depression and dysthymia. J Clin Psychopharmacol. 1993; 13:133-44. http://www.ncbi.nlm.nih.gov/pubmed/8463446?dopt=AbstractPlus

130. Dufresne RL, Weber SS, Becker RE. Bupropion hydrochloride. Drug Intell Clin Pharm. 1984; 18:957-64. http://www.ncbi.nlm.nih.gov/pubmed/6439541?dopt=AbstractPlus

131. James WA, Lippmann S. Bupropion: overview and prescribing guidelines in depression. South Med J. 1991; 84:222-4. http://www.ncbi.nlm.nih.gov/pubmed/1899294?dopt=AbstractPlus

132. Potter WZ, Rudorfer MV, Manji H. The pharmacologic treatment of depression. N Engl J Med. 1991; 325:633-42. http://www.ncbi.nlm.nih.gov/pubmed/1861697?dopt=AbstractPlus

133. National Institutes of Health Office of Medical Applications of Research. Consensus conference: diagnosis and treatment of depression in late life. JAMA. 1992; 268:1018-24. http://www.ncbi.nlm.nih.gov/pubmed/1501308?dopt=AbstractPlus

134. Settle EC Jr. Bupropion: a novel antidepressant–update 1989. Int Drug Ther Newsl. 1989; 24:29-36.

135. Weintraub M, Evans P. Bupropion: a chemically and pharmacologically unique antidepressant. Hosp Formul. 1989; 24:254-9.

136. Malesker MA, Soori GS, Malone PM et al. Eosinophilia associated with bupropion. Ann Pharmacother. 1995; 29:867-8. http://www.ncbi.nlm.nih.gov/pubmed/8547734?dopt=AbstractPlus

137. Sweet RA, Pollock BG, Kirshner M et al. Pharmacokinetics of single- and multiple-dose bupropion in elderly patients with depression. J Clin Pharmacol. 1995; 35:876-84. http://www.ncbi.nlm.nih.gov/pubmed/8786247?dopt=AbstractPlus

138. Ketter TA, Jenkins JB, Schroeder DH et al. Carbamazepine but not valproate induces bupropion metabolism. J Clin Psychopharmacol. 1995; 15:327-33. http://www.ncbi.nlm.nih.gov/pubmed/8830063?dopt=AbstractPlus

139. Glaxo Wellcome, Inc, Research Triangle Park, NC: Personal communication.

140. Reviewers’ comments (personal observations).

141. Ayd FJ. safest antidepressant for epileptics and the seizure prone. Int Drug Ther Newsl. 1995; 30:29-32.

142. GlaxoSmithKline. Wellbutrin SR (bupropion hydrochloride) sustained-release tablets prescribing information. Research Triangle Park, NC; 2022 Dec. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=cbc8c074-f080-4489-a5ae-207b5fadeba3

143. Dr. Reddy's Laboratories Inc. Bupropion hydrochloride sustained-release tablets prescribing information. Princeton, NJ; 2022 Jun. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8069c521-c49a-4b6d-baa8-4b0be897d585%20

144. Shad MU, Preskorn SH. A possible bupropion and imipramine interaction. J Clin Psychopharmacol. 1997; 17:118-9. http://www.ncbi.nlm.nih.gov/pubmed/10950476?dopt=AbstractPlus

145. Hurt RD, Sachs DPL, Glover Ed et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med. 1997; 337:1195-202. http://www.ncbi.nlm.nih.gov/pubmed/9337378?dopt=AbstractPlus

146. Benowitz NL. Treating tobacco addiction—nicotine or no nicotine? N Engl J Med. 1997; 337:1230-1. Editorial.

147. Ascher JA, Cole JO, Colin JN et al. Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry. 1995; 56:395-40. http://www.ncbi.nlm.nih.gov/pubmed/7665537?dopt=AbstractPlus

148. American Psychiatric Association Work Group on Nicotine Dependence. Practice guideline for the treatment of patients with nicotine dependence. Am J Psychiatry. 1996; 153(Suppl Oct):1-31.

149. US Department of Health, Education, and Welfare. US Surgeon General’s report on smoking and health. DHEW Publ. No. [PHS] 79-50066. Washington, DC: US Government Printing Office; 1979:1-1164.

150. Jusko WJ. Role of tobacco smoking in pharmacokinetics. J Pharmacokinet Biopharm. 1978; 6:7-39. http://www.ncbi.nlm.nih.gov/pubmed/349132?dopt=AbstractPlus

151. Lee BL, Benowitz NL, Jacob P III. Cigarette abstinence, nicotine gum, and theophylline disposition. Ann Intern Med. 1987; 106:553-5. http://www.ncbi.nlm.nih.gov/pubmed/3826954?dopt=AbstractPlus

152. Fiore MC, Jaén CR, Baker TB, et al. Treating tobacco use and dependence: 2008 update. Clinical Practice Guideline. Rockville, MD: US Department of Health and Human Services, Public Health Service. 2008 May.

153. American Psychiatric Association. Practice guideline for the treatment of patients with eating disorders (revision). Am J Psychiatry. 2000; 157(suppl 1):1-39.

154. American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002; 159(Suppl):1-50.

155. Frances AJ, Kahn DA, Carpenter D et al. The Expert Consensus Guidelines for treating depression in bipolar disorder. J Clin Psychiatry. 1998; 59(Suppl 4):73-9. http://www.ncbi.nlm.nih.gov/pubmed/9554324?dopt=AbstractPlus

156. Pliszka SR, Greenhill LL, Crismon ML et al. The Texas Children’s Medication Algorithm Project: Report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Attention-Deficit/Hyperactivity Disorder. Part II: Tactics. J Am Acad Child Adolesc Psychiatry. 2000; 39:920-7. http://www.ncbi.nlm.nih.gov/pubmed/10892235?dopt=AbstractPlus

157. Dulcan M, Dunne JE, Ayres W et al. Practice parameters for the assessment and treatment of children, adolescents, adults with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatr. 1997; 10(Suppl):85-121S.

158. American Academy of Pediatrics Committee on Quality Improvement and Subcommittee on Attention-Deficit/Hyperactivity Disorder. Clinical treatment guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder. Pediatrics. 2001; 108:1033-44. http://www.ncbi.nlm.nih.gov/pubmed/11581465?dopt=AbstractPlus

159. Jorenby DE, Leischow SJ, Nides MA et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1997; 337:1195-202. http://www.ncbi.nlm.nih.gov/pubmed/9337378?dopt=AbstractPlus

160. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder: third edition. Published 2010 Oct. Available at Psychiatry Online web site. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd-1410197717630.pdf

161. Food and Drug Administration. Antidepressant use in children, adolescents, and adults: class revisions to product labeling. Rockville, MD; 2007 May 2. From the FDA web site. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm096273.htm

162. Food and Drug Administration. FDA news: FDA proposes new warnings about suicidal thinking, behavior in young adults who take antidepressant medications. Rockville, MD; 2007 May 2. From the FDA web site. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108905.htm

163. Anon. FDA statement on recommendations of the psychopharmacologic drugs and pediatric advisory committees. Rockville, MD; 2004 Sep 16. From the FDA web site:. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108352.htm

164. American Psychiatric Association (APA). APA responds to FDA’s new warning on antidepressants. Arlington, VA; 2004 Oct. 15. From the APA web site. http://pn.psychiatryonline.org

165. American Academy of Child and Adolescent Psychiatry (AACAP). AACAP responds to the new FDA warnings on pediatric antidepressant medications. Washington, D.C; 2004 Oct 15. From the AACAP web site. http://www.aacap.org/cs/root/media/press_releases/2004_press_releases/aacap_responds_to_new_fda_warnings_on_pediatric_antidepressant_medication

166. American Academy of Pediatrics (AAP). Children, antidepressants and a black box warning. Washington, D.C; 2004 Oct. 15. From the AAP web site. http://www.aap.org/pressroom/aappr-pressreleases.htm

167. Food and Drug Administration. Revisions to medication guide: antidepressant medicines, depression and other serious mental illnesses and suicidal thoughts or actions. Rockville, MD; 2007 May 2. From the FDA web site. http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/ucm100211.pdf

168. Bausch Health US, LLC. Wellbutrin XL (bupropion hydrochloride) extended-release tablets prescribing information. Bridgewater, NJ; 2022 Mar. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a435da9d-f6e8-4ddc-897d-8cd2bf777b21

169. Modell JG, Rosenthal NE, Harriett AE et al. Seasonal affective disorder and its prevention by anticipatory treatment with bupropion XL. Biol Psychiatry. 2005; 58:658-67. http://www.ncbi.nlm.nih.gov/pubmed/16271314?dopt=AbstractPlus

170. Dilsaver SC, Qamar AB, Del Medico VJ et al. The efficacy of bupropion in winter depression: results of an open trial. J Clin Psychiatry. 1992; 53:252-5. http://www.ncbi.nlm.nih.gov/pubmed/1639745?dopt=AbstractPlus

171. Dilsaver SC, Del Medico VJ, Quadri A et al. Pharmacological responsiveness of winter depression. Psychopharmacol Bull. 1990; 26:303-9. http://www.ncbi.nlm.nih.gov/pubmed/2125735?dopt=AbstractPlus

172. Odishaw J, Chen C. Effects of steady-state bupropion on the pharmacokinetics of lamotrigine in healthy subjects. Pharmacotherapy. 2000; 20:1448-53. http://www.ncbi.nlm.nih.gov/pubmed/11130217?dopt=AbstractPlus

173. Hesse LM, von Moltke LL, Shader RI et al. Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion. Drug Metab Dispos. 2001; 29:100-2. http://www.ncbi.nlm.nih.gov/pubmed/11159797?dopt=AbstractPlus

174. Hesse LM, Venkatakrishnan K, Court MH et al. CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metab Dispos. 2000; 28:1176-83. http://www.ncbi.nlm.nih.gov/pubmed/10997936?dopt=AbstractPlus

175. Cole JA, Modell JG, Haight BR et al. Bupropion in pregnancy and the prevalence of congenital malformations. Pharmacoepidemiol Drug Saf. (in press).

176. Drutelka D, Zed PJ. Cardiotoxicity following bupropion overdose. Ann Pharmacother. 2002; 36:1791-5. http://www.ncbi.nlm.nih.gov/pubmed/12398578?dopt=AbstractPlus

177. Worrall SP, Almond MK, Dhillon S. Pharmacokinetics of bupropion and its metabolites in haemodialysis patients who smoke: a single dose study. Nephron Clin Pract. 2004; 97:c83-9. http://www.ncbi.nlm.nih.gov/pubmed/15292684?dopt=AbstractPlus

178. Modell JG, Katholi CR, Modell JD et al. Comparative sexual side effects of bupropion, fluoxetine, paroxetine, and sertraline. Clin Pharmacol Ther. 1997; 61:476-87. http://www.ncbi.nlm.nih.gov/pubmed/9129565?dopt=AbstractPlus

179. Trivedi MH, Fava M, Wisniewski SR et al. for the STAR*D Study Team. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006; 354:1243-52. http://www.ncbi.nlm.nih.gov/pubmed/16554526?dopt=AbstractPlus

180. Rush AJ, Trivedi MH, Wisniewski SR et al. for the STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006; 354:1231-42. http://www.ncbi.nlm.nih.gov/pubmed/16554525?dopt=AbstractPlus

181. Bridge JA, Iyengar S, Salary CB. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007; 297:1683-96. http://www.ncbi.nlm.nih.gov/pubmed/17440145?dopt=AbstractPlus

186. Food and Drug Administration. FDA Alert: Information for healthcare professionals: varenicline (marketed as Chantix) and bupropion (marketed as Zyban, Wellbutrin, and generics). Rockville, MD; 2009 Jul 1. From the FDA web site. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm169986.htm

187. Food and Drug Administration. FDA News: Boxed warning on serious mental health events to be required for Chantix and Zyban. Rockville, MD; 2009 Jul 1. From the FDA web site. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm170100.htm

188. Pollock M, Lee JH. The smoking cessation aids varenicline (marketed as Chantix) and bupropion (marketed as Zyban and generics): suicidal ideation and behavior. Drug Safety Newsletter. 2009; 2:1–4. From the FDA web site. http://www.fda.gov/downloads/Drugs/DrugSafety/DrugSafetyNewsletter/UCM107318.pdf

189. Food and Drug Administration. Public Health Advisory: FDA requires new boxed warnings for the smoking cessation drugs Chantix and Zyban. Rockville, MD; 2009 Jul 1. From the FDA web site. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm169988.htm

190. Food and Drug Administration. FDA requires new boxed warnings for the smoking cessation drugs Chantix and Zyban. Rockville, MD; 2009 Jul 1. From the FDA web site. http://www.fda.gov/Drugs/DrugSafety/DrugSafetyPodcasts/ucm170906.htm

224. US Food and Drug Administration. FDA Drug Safety Communication: FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. Rockville, MD; 2016 Dec 16. From FDA website. Accessed 2023 May 18. https://www.fda.gov/Drugs/DrugSafety/ucm532221.htm

225. 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; 387:2507-20. http://www.ncbi.nlm.nih.gov/pubmed/27116918?dopt=AbstractPlus

226. Almatica Pharma, Inc. Forfivo XL (bupropion hydrochloride) extended-release tablets prescribing information. Pine Brook, NJ; 2019 Dec. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022497s008lbl.pdf

227. Bausch Health US, LLC. Aplenzin (bupropion hydrobromide) extended-release tablets prescribing information. Bridgewater, NJ; 2022 Mar. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6494d2d9-0ce4-4126-b1c7-49684395942b

228. Verbeeck W, Bekkering GE, Van den Noortgate W et al. Bupropion for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2017; 10:CD009504. http://www.ncbi.nlm.nih.gov/pubmed/28965364?dopt=AbstractPlus

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