What are the potential side effects of Bupropion (Wellbutrin)

Bupropion Side Effects

Bupropion is generally well-tolerated with common side effects including insomnia, dry mouth, headache, nausea, and anxiety, but carries a critical seizure risk (approximately 0.1% at recommended doses) that requires careful patient screening for predisposing factors. 1, 2

Common Side Effects

The most frequently reported adverse effects with bupropion include:

• Insomnia and dry mouth are the most common side effects, occurring significantly more often than placebo, though they are typically transient and often resolve without intervention 3, 2
• Neurological effects including headache, dizziness, tremor, and feeling "jittery" or anxious are frequently reported 2, 3
• Gastrointestinal effects such as nausea, constipation, vomiting, and dry mouth occur commonly 2, 3
• Cardiovascular effects including tachycardia and palpitations may occur, though serious dysrhythmias are rare 2
• Joint aches and stuffy nose are also reported 4

A key clinical advantage: bupropion has significantly lower rates of sexual dysfunction compared to SSRIs and minimal weight gain, making it particularly suitable for patients concerned about these side effects 1, 5

Serious Side Effects Requiring Immediate Attention

Seizure Risk

The seizure risk is approximately 0.1% (1 in 1,000) at the recommended maximum dose of 300 mg/day when patients are properly screened, but this risk increases substantially with higher doses or in patients with predisposing factors 3, 2

Absolute contraindications for seizure risk include: 2

• Prior history of seizures or structural brain lesions (stroke, tumor, trauma)
• Brain metastases 1
• Eating disorders (anorexia nervosa or bulimia nervosa) due to electrolyte disturbances
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2

If a patient develops a seizure while on bupropion, immediately discontinue the medication and do not restart 4

Neuropsychiatric Effects

Monitor closely for new or worsening psychiatric symptoms, particularly in the first several weeks of treatment: 1, 4

• Depression and suicidal ideation/behavior (especially in patients under age 24)
• Agitation, hostility, or aggressive behavior
• Anxiety or panic attacks
• Mania or hypomania (particularly in patients with undiagnosed bipolar disorder)

These effects are uncommon but require immediate discontinuation if they occur, particularly suicidal thoughts or severe behavioral changes 1, 4

Cardiovascular Effects

• Hypertension can occur and may be severe, especially when combined with nicotine replacement therapy 4, 2
• Monitor blood pressure regularly, particularly during the first 12 weeks of treatment 2
• Bupropion should be used with caution in patients with cardiovascular disease and avoided in those with uncontrolled hypertension 2

Hypersensitivity Reactions

Delayed allergic reactions can occur, sometimes appearing 2 or more weeks after initiation (median onset around day 28), presenting as: 6

• Pruritus (itching)
• Urticaria (hives)
• Rash on extremities and back

Risk appears highest in males aged 17-40 years and those with a history of allergic reactions 6. If hypersensitivity develops, taper bupropion over 7 days and consider antihistamine treatment 6.

Critical Drug Interactions and Contraindications

Absolute contraindications include: 2, 4

• Concurrent use with MAO inhibitors or within 14 days of discontinuing MAOIs (risk of hypertensive crisis)
• Concurrent use with tamoxifen (bupropion inhibits CYP2D6, reducing tamoxifen efficacy) 1
• Patients with closed-angle glaucoma 1

Bupropion inhibits CYP2D6, raising concern for clinically relevant drug interactions with medications metabolized by this pathway 7

Dosing Considerations to Minimize Side Effects

To minimize seizure risk: 2, 4

• Never exceed 300 mg/day for smoking cessation or 450 mg/day for depression
• Ensure doses are spaced at least 24 hours apart for XL formulation 4
• Do not crush, chew, or cut extended-release tablets (releases medication too quickly, increasing seizure risk) 4

To minimize insomnia: 5, 2

• Administer the second dose of SR formulation before 3 PM
• Avoid taking XL formulation too close to bedtime 4

Special Populations

For smoking cessation in cancer patients: 1

• Nausea may be particularly problematic during chemotherapy and may need management
• Contraindicated in patients with brain metastases due to seizure risk

Alcohol use requires special attention: 4

• Limit or avoid alcohol during treatment
• If patient usually drinks heavily, do not abruptly stop alcohol (increases seizure risk)—coordinate with healthcare provider for safe alcohol cessation

Management of Common Side Effects

Most common side effects (insomnia, dry mouth) are generally transient and can be managed by: 3

• Dose reduction if necessary
• Timing adjustments (earlier dosing for insomnia)
• Symptomatic treatment (e.g., sugar-free gum for dry mouth)

Discontinuation rates due to adverse events are low (6-12%) in clinical trials, indicating overall good tolerability 3

Warning Signs Requiring Immediate Medical Attention

Patients should contact their provider immediately if they experience: 4, 8

• Seizure activity
• Severe agitation or "jittery" feeling (83% of patients who developed seizures or serious adverse events reported feeling jittery/anxious/agitated) 8
• New or worsening suicidal thoughts
• Severe allergic reactions (rash, hives, difficulty breathing)
• Chest pain or severe palpitations
• Severe hypertension symptoms (severe headache, vision changes)