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

Bupropion Side Effects

Bupropion commonly causes insomnia, dry mouth, headache, nausea, and dizziness, but the most critical concern is seizure risk (approximately 0.1% at recommended doses), which requires careful screening for predisposing factors before prescribing. 1, 2

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, nausea, constipation, and vomiting occur regularly 1
• Psychiatric effects: Anxiety and agitation, though these can overlap with nicotine withdrawal symptoms in smoking cessation patients 3

Only insomnia and dry mouth occur significantly more frequently with bupropion compared to placebo, and most common side effects are generally transient and often resolve within days without intervention 3, 2. If management is needed, dose reduction or timing adjustments (such as taking the second dose before 3 PM) can minimize insomnia 1.

Serious Side Effects Requiring Immediate Attention

Seizure Risk

The seizure incidence is approximately 0.1% (1 in 1,000) at the maximum recommended dose of 300 mg/day when patients are properly screened, but this risk increases substantially with higher doses or in the presence of predisposing factors 2, 4.

Absolute contraindications for seizure risk include: 1, 2

• Prior history of seizures or structural brain lesions (stroke, tumor, trauma, brain metastases)
• Current eating disorders (anorexia nervosa or bulimia nervosa) due to electrolyte disturbances
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
• Concomitant medications that lower seizure threshold

If a seizure occurs while taking bupropion, stop the medication immediately and do not restart it. 4

Cardiovascular Effects

• Hypertension: Bupropion can cause elevated blood pressure, which may be severe, particularly when combined with nicotine replacement therapy 1, 4
• Tachycardia and tachyarrhythmias: Heart rate increases and rhythm disturbances can occur 1
• Blood pressure and heart rate should be monitored periodically, especially during the first 12 weeks of treatment 1

Neuropsychiatric Effects

Serious mental health changes can occur, including: 4

• New or worsening depression
• Suicidal thoughts or actions (particularly in patients under 24 years)
• Agitation, hostility, or aggression
• Panic attacks
• Mania or hypomania (especially in patients with bipolar disorder or family history)

These symptoms may appear when starting bupropion, after several weeks of treatment, or even after stopping the medication. Patients with a history of mental health problems are at higher risk. 4

Hypersensitivity Reactions

Severe allergic reactions occur in approximately 0.1% of patients and require immediate discontinuation 2, 3.

Critical Drug Interactions and Contraindications

Absolute contraindications include: 2

• Concurrent use with MAO inhibitors or within 14 days of discontinuing MAOIs (risk of hypertensive crisis)
• Concurrent use with tamoxifen
• Patients with closed-angle glaucoma

Bupropion inhibits CYP2D6 and can raise plasma levels of antidepressants, antiarrhythmics, and antipsychotics, requiring dose adjustments of these medications 5, 6.

Advantages Compared to Other Antidepressants

Bupropion has significantly lower rates of sexual dysfunction compared to SSRIs and causes minimal weight gain, making it particularly suitable for patients concerned about these side effects 2, 7. This represents a major clinical advantage in long-term adherence.

Special Population Considerations

Hepatic Impairment

• Maximum dose is 150 mg every other day in moderate to severe hepatic impairment (Child-Pugh score 7-15) 4
• Consider dose reduction in mild hepatic impairment 4

Renal Impairment

• Reduce total daily dose by half in moderate to severe renal impairment (GFR <90 mL/min) as bupropion metabolites accumulate 8

Alcohol Use

Patients who regularly drink heavily require special attention: coordinate with them for safe alcohol cessation before starting bupropion, as abrupt alcohol discontinuation dramatically increases seizure risk 2. Recommend limiting or avoiding alcohol during treatment 2.

Warning Signs Requiring Immediate Medical Attention

Contact healthcare provider immediately if experiencing: 2

• Any seizure activity
• Severe agitation or "jittery" feeling
• Chest pain or severe palpitations
• Severe hypertension symptoms
• New or worsening suicidal thoughts
• Severe allergic reactions (rash, difficulty breathing, swelling)

Common Pitfalls to Avoid

• Never exceed 300 mg/day for smoking cessation or 450 mg/day for depression to minimize seizure risk 1, 7
• Do not crush or inject bupropion tablets - this has been associated with seizures and death 4
• Screen carefully for eating disorders - patients may not volunteer this information, but it represents an absolute contraindication 1, 2
• Assess alcohol and benzodiazepine use thoroughly - abrupt discontinuation while on bupropion is extremely dangerous 1, 2