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

Wellbutrin (Bupropion) Side Effects

Wellbutrin commonly causes insomnia, dry mouth, headache, nausea, and anxiety, with insomnia and dry mouth being the only side effects occurring significantly more frequently than placebo. 1, 2

Common Side Effects

The most frequently reported adverse effects include:

• Insomnia - the most common side effect, often transient and may resolve without intervention 2
• Dry mouth - second most common, generally transient 2
• Headache - frequently reported in clinical trials 2
• Nausea - occurs less commonly than with SSRIs 3
• Anxiety and agitation - though these can also represent nicotine withdrawal symptoms in smoking cessation patients 2

These common side effects typically resolve quickly without therapeutic intervention, though dose reduction can be considered if management is needed. 2

Serious Side Effects Requiring Immediate Attention

Seizure Risk

• The seizure incidence is approximately 0.1% (1 in 1,000) when the maximum daily dose of 450 mg is not exceeded 4, 5
• Seizure risk increases with higher doses, certain medical conditions, and concomitant medications 1
• Bupropion must be avoided entirely in patients with seizure disorders, brain metastases, eating disorders (bulimia/anorexia), or other conditions that lower seizure threshold 4, 6, 5
• If a seizure occurs, discontinue bupropion immediately and permanently - do not restart 1

Neuropsychiatric Effects

• Suicidal thoughts or behaviors can occur, particularly in young adults under age 24 4, 1
• New or worsening mental health symptoms including depression, aggression, hostility, agitation, or behavioral changes may develop 1
• These symptoms can appear when starting treatment, after several weeks, or even after stopping bupropion 1
• Patients with a history of mental health problems face higher risk 1

Cardiovascular Effects

• Hypertension can develop and may be severe, especially when combined with nicotine replacement therapy 1
• Blood pressure monitoring is essential, and bupropion should be avoided in patients with uncontrolled hypertension 6
• Bupropion appears to have lower cardiovascular event risk compared to venlafaxine 4

Hypersensitivity Reactions

• Severe allergic reactions occur in approximately 0.1% of patients 2
• Delayed hypersensitivity reactions (pruritus, urticaria) can appear 2 or more weeks after initiation, making recognition challenging 7
• Risk may be highest in males aged 17-40 years with a history of allergic reactions 7
• Discontinue bupropion if allergic symptoms develop 7

Favorable Side Effect Profile

• Bupropion has the lowest rate of sexual dysfunction among antidepressants, significantly lower than SSRIs like fluoxetine or sertraline 4, 3
• Anticholinergic effects, orthostatic hypotension, and cardiac conduction abnormalities occur less frequently than with tricyclic antidepressants 3, 8
• Weight gain is minimal compared to other antidepressants 6

Critical Drug Interactions and Contraindications

• Never use bupropion with MAOIs or within 14 days of stopping MAOIs 4, 6
• Bupropion inhibits CYP2D6, raising concern for drug interactions 3
• Avoid in patients taking tamoxifen 6

Special Population Dosing to Minimize Side Effects

• Moderate to severe hepatic impairment: maximum 150 mg daily 4, 6, 1
• Moderate to severe renal impairment: reduce total daily dose by 50% 4, 6
• Older adults: start with 37.5 mg daily, increase gradually by 37.5 mg every 3 days, maximum 300 mg/day 6
• Administer second daily dose before 3 PM to minimize insomnia 6

Overdose Considerations

• Seizures occur in approximately one-third of bupropion overdoses 1
• Other serious overdose effects include hallucinations, loss of consciousness, cardiac arrhythmias, and respiratory failure 1
• Deaths have been reported with large ingestions, though most patients recover without sequelae 1
• No specific antidote exists; treatment is supportive 1

Clinical Pearls

• Start with gradual titration (150 mg daily for 3 days, then 150 mg twice daily) to minimize seizure risk while achieving therapeutic levels 6, 5
• The insoluble shell of extended-release tablets may appear intact in stool - this is normal 1
• Bupropion should never be crushed, inhaled, or injected - seizures and deaths have been reported with these routes 1
• Discontinuation rates due to adverse events are low (6-12%) in clinical trials 2