What are the potential side effects of Wellbutrin (bupropion)?

Side Effects of Wellbutrin (Bupropion)

Wellbutrin commonly causes dry mouth, insomnia, headache, nausea, constipation, dizziness, and tremor, with the most serious risk being seizures occurring at a rate of approximately 0.1% (1 in 1,000) at therapeutic doses when patients are properly screened and dosing guidelines are followed. 1

Common Side Effects

The most frequently reported adverse effects include:

• Neurological effects: Insomnia, headache, dizziness, and tremor are among the most common complaints 1
• Gastrointestinal effects: Dry mouth (the single most common side effect), nausea, constipation, and vomiting occur frequently 1, 2
• Cardiovascular effects: Tachycardia and elevated blood pressure can occur, requiring periodic monitoring especially during the first 12 weeks of treatment 1, 3

These common side effects are generally transient and often resolve within 4-5 days without therapeutic intervention, though dose reduction may be necessary if symptoms persist 4, 5

Serious Side Effects Requiring Immediate Attention

Seizure Risk

• The baseline seizure risk is approximately 0.1% (1 in 1,000) at the maximum recommended dose of 300 mg/day for smoking cessation or 450 mg/day for depression 6, 1
• Risk factors that dramatically increase seizure likelihood include: prior seizure history, structural brain lesions (stroke, tumor, trauma), eating disorders (bulimia/anorexia nervosa), alcohol abuse, and medications that lower seizure threshold 1
• If a seizure occurs, stop bupropion immediately and never restart it 7

Neuropsychiatric Effects

• Black box warning exists for increased risk of suicidal thoughts and behavior, particularly in patients under age 24 1, 7
• New or worsening depression, anxiety, agitation, panic attacks, irritability, aggression, mania, or behavioral changes require immediate medical attention 7
• These symptoms can emerge when starting treatment, after dose changes, or even after several weeks of stable therapy 7

Cardiovascular Effects

• Hypertension can develop and may be severe, especially when combined with nicotine replacement therapy 7
• Blood pressure and heart rate must be monitored periodically, particularly during the first 12 weeks 6, 1
• Tachyarrhythmias ranging from mild to severe have been reported 1

Hypersensitivity Reactions

• Severe allergic reactions occur at approximately 0.1% incidence in controlled trials 4
• These are medically important adverse events requiring immediate discontinuation 2

Absolute Contraindications

Do not use bupropion in patients with:

• History of seizures from any cause, including alcohol withdrawal 6, 1
• Current or history of eating disorders (bulimia or anorexia nervosa) due to dramatically increased seizure risk 1, 3
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1, 7
• Current use of MAOIs or within 14 days of discontinuing MAOIs (risk of hypertensive crisis) 1, 3
• Uncontrolled hypertension 1, 3
• Concurrent opioid therapy when using naltrexone-bupropion combination products 3

Special Population Considerations

Hepatic Impairment

• Maximum dose is 150 mg every other day for moderate to severe hepatic impairment (Child-Pugh score 7-15) 3, 7
• Consider dose reduction for mild hepatic impairment (Child-Pugh score 5-6) 3, 7

Renal Impairment

• Reduce total daily dose by 50% for moderate to severe renal impairment 3
• Bupropion and metabolites are cleared renally and may accumulate 3

Pregnancy and Breastfeeding

• Limited data suggest no major congenital malformations, though small increases in specific cardiovascular defects have been reported 3
• Bupropion is present in breast milk at low levels; two case reports of seizures in breastfed infants warrant caution 3

Advantages Over Other Antidepressants

Despite these side effects, bupropion has several favorable characteristics:

• Significantly lower rates of sexual dysfunction compared to SSRIs 3, 2
• Minimal weight gain or even weight loss, unlike many other antidepressants 3, 2
• Lower rates of sedation than SSRIs 3
• No significant anticholinergic effects beyond dry mouth 8
• 10 to 100 times less likely to cause cardiac conduction problems than tricyclic antidepressants 8

Critical Monitoring Requirements

• Screen for seizure risk factors before initiating therapy 1, 4
• Assess alcohol consumption patterns and screen for eating disorders 6, 1
• Monitor blood pressure and heart rate, especially during first 12 weeks 6, 1
• Watch for emergence of suicidal thoughts, particularly in patients under 24 years 1, 7
• Monitor for neuropsychiatric symptoms including agitation, behavioral changes, and mood shifts 1, 7

Common Pitfalls to Avoid

• Never exceed maximum doses: 300 mg/day for smoking cessation, 400 mg/day for SR formulation, or 450 mg/day for XL formulation to maintain seizure risk at 0.1% 1, 3
• Do not administer second dose after 3 PM to minimize insomnia risk 3
• Never abruptly discontinue without consulting healthcare provider 7
• Do not crush, inject, or insufflate tablets—seizures and deaths have been reported with these routes 7