What are the contraindications to Wellbutrin (bupropion) in patients with a history of seizure disorders, eating disorders, head trauma, brain tumor, stroke, or monoamine oxidase inhibitor (MAOI) use, and impaired hepatic or renal function?

Contraindications to Wellbutrin (Bupropion)

Wellbutrin is absolutely contraindicated in patients with seizure disorders, current or prior eating disorders (bulimia or anorexia nervosa), abrupt discontinuation of alcohol/benzodiazepines/barbiturates/antiepileptic drugs, concurrent MAOI use (or within 14 days), and known hypersensitivity to bupropion. 1

Absolute Contraindications

Seizure-Related Contraindications

• Any history of seizure disorder is an absolute contraindication to bupropion use 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs creates seizure risk and contraindicates bupropion 1
• The seizure risk with bupropion is dose-dependent, occurring at approximately 0.1% at doses ≤300 mg/day and approximately 0.4% at 400-450 mg/day 2
• Seizures have been documented even at moderate doses (600 mg/day) and modest blood levels (83 ng/ml) in patients without predisposing factors 3

Eating Disorder Contraindications

• Current or prior diagnosis of bulimia nervosa or anorexia nervosa is an absolute contraindication due to significantly higher seizure incidence 1
• In clinical trials of bulimic patients, 4 out of 55 subjects (7.3%) experienced grand mal seizures on bupropion—a rate far exceeding that seen in other populations 4
• The mechanism appears related to electrolyte disturbances and metabolic abnormalities common in eating disorders that further lower seizure threshold 5, 4

MAOI Contraindications

• Concurrent use with MAOIs intended to treat psychiatric disorders is contraindicated due to hypertensive crisis risk 1
• Use within 14 days of discontinuing an MAOI or starting bupropion after stopping an MAOI is contraindicated 1
• Concurrent use with reversible MAOIs (linezolid or intravenous methylene blue) is contraindicated 1
• At least 14 days must elapse between discontinuing an MAOI and starting bupropion, and vice versa 1

Hypersensitivity Contraindications

• Known hypersensitivity to bupropion or any ingredient in the formulation is an absolute contraindication 1
• Anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have been reported with bupropion 1

Conditions Requiring Extreme Caution or Avoidance

Cardiovascular Contraindications

• Uncontrolled hypertension should preclude bupropion use, as the medication can elevate blood pressure and heart rate 6, 7
• Blood pressure must be monitored before initiating treatment and periodically during therapy, especially in the first 12 weeks 2, 7
• Both bupropion and naltrexone-bupropion combinations are contraindicated in uncontrolled hypertension 7

Hepatic Impairment Dosing Restrictions

• Moderate to severe hepatic impairment (Child-Pugh score 7-15): Maximum dose is 150 mg every other day 2, 1
• Mild hepatic impairment (Child-Pugh score 5-6): Reduce dose and/or frequency 2, 1
• Bupropion undergoes extensive hepatic metabolism via CYP2B6, necessitating these restrictions 8

Renal Impairment Dosing Restrictions

• Moderate to severe renal impairment (GFR <90 mL/min): Reduce total daily dose by 50% 2
• End-stage renal disease: Bupropion should be avoided 2
• Bupropion and its active metabolites are cleared renally and may accumulate with impaired function 2

Pregnancy and Breastfeeding Concerns

• Pregnancy: All weight management formulations containing bupropion are contraindicated in women who are or may become pregnant 2, 7
• Limited data suggest no major congenital malformations, though small increases in specific cardiovascular defects have been reported 2
• Breastfeeding: Bupropion is present in breast milk at low levels, with two case reports of seizures in breastfed infants warranting caution 2

Critical Clinical Warnings

Black Box Warning

• Increased risk of suicidal thoughts and behavior in patients younger than 24 years with depression requires close monitoring, especially during the first few months of treatment 2, 7, 1
• The risk for suicide attempts is greatest during the first 1-2 months of treatment 2

Conditions That Lower Seizure Threshold

• Head trauma, brain tumor, stroke, or any condition predisposing to seizures warrants extreme caution or avoidance beyond those explicitly contraindicated 2
• Dose bupropion with extreme caution when combining with other drugs that lower seizure threshold 6, 1
• The maximum dose should not exceed 450 mg per day (XL formulation) or 400 mg per day (SR formulation) to minimize seizure risk 2

Drug Interaction Contraindications

• Chronic opioid therapy: Contraindicated when using naltrexone-bupropion combination 6, 2
• Tamoxifen use: Bupropion inhibits CYP2D6 and may reduce tamoxifen efficacy; avoid concurrent use 2
• CYP2D6 substrates: Bupropion inhibits CYP2D6 and can increase concentrations of antidepressants (venlafaxine, nortriptyline, paroxetine, fluoxetine, sertraline), antipsychotics (haloperidol, risperidone), beta-blockers (metoprolol), and Type 1C antiarrhythmics (propafenone, flecainide); consider dose reduction 6, 1

Common Pitfalls to Avoid

• Do not prescribe bupropion without screening for eating disorder history, as even remote history of bulimia or anorexia nervosa is a contraindication 2, 1
• Do not combine with MAOIs or start within 14 days of MAOI discontinuation, as hypertensive crisis can occur 6, 1
• Do not exceed maximum daily doses (450 mg XL or 400 mg SR) to maintain seizure risk at acceptable levels 2
• Do not abruptly discontinue alcohol or sedatives in patients on bupropion, as this dramatically increases seizure risk 1
• Do not ignore blood pressure monitoring, especially in the first 12 weeks, as bupropion can cause significant elevations 2, 7