What are the contraindications to Wellbutrin (bupropion)?

Contraindications to Wellbutrin (Bupropion)

Wellbutrin is absolutely contraindicated in patients with seizure disorders, current or prior bulimia or anorexia nervosa, those undergoing 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 current or prior seizure disorder is an absolute contraindication due to bupropion's dose-dependent reduction of seizure threshold 1
• Current or prior diagnosis of bulimia or anorexia nervosa due to significantly higher seizure incidence observed in these populations 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs creates an absolute contraindication due to dramatically increased seizure risk 1, 2

Drug Interaction Contraindications

• Concurrent use with MAOIs (monoamine oxidase inhibitors) or within 14 days of discontinuing either bupropion or an MAOI, due to increased risk of hypertensive reactions 1
• Starting bupropion in patients currently on reversible MAOIs such as linezolid or intravenous methylene blue is contraindicated 1
• Chronic opioid therapy when considering naltrexone/bupropion combination products 3, 2

Hypersensitivity Contraindications

• Known hypersensitivity to bupropion or any ingredients in the formulation, as anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have been reported 1

Relative Contraindications and High-Risk Situations

Cardiovascular Conditions

• Uncontrolled hypertension should preclude bupropion use, particularly with naltrexone/bupropion combinations, as the medication can elevate blood pressure and heart rate 3

Conditions Predisposing to Seizures

While not absolute contraindications per FDA labeling, the following significantly increase seizure risk and warrant extreme caution or avoidance:

• Any condition that predisposes to seizures beyond those explicitly contraindicated 3
• Doses exceeding 450 mg/day (for XL formulation) or 400 mg/day (for SR formulation), as seizure risk increases substantially above these thresholds 2
• Concurrent medications that lower seizure threshold require careful evaluation 4, 5

Hepatic and Renal Impairment

• Moderate to severe hepatic impairment requires dose reduction to maximum 150 mg daily, though not an absolute contraindication 2
• Moderate to severe renal impairment (GFR <90 mL/min) requires 50% dose reduction due to accumulation of bupropion and metabolites 2

Critical Clinical Pearls

Black Box Warning: Bupropion carries an FDA black box warning for increased risk of suicidal thoughts and behavior in patients younger than 24 years with depression, requiring close monitoring especially during the first few months of treatment 3

Seizure Risk Context: At therapeutic doses (≤450 mg/day in divided doses), seizure incidence is comparable to other antidepressants (less than 1 per 1,000 at outpatient doses), but risk escalates dramatically with higher doses, rapid titration, or presence of risk factors 4, 6

Drug Interaction with Tamoxifen: The National Comprehensive Cancer Network contraindicates bupropion in patients taking tamoxifen due to metabolic interactions 2

Pregnancy Status: All weight management formulations containing bupropion are contraindicated in women who are or may become pregnant, requiring reliable contraception counseling 3