Wellbutrin (Bupropion): Indications, Dosing, and Contraindications
Wellbutrin (bupropion) is FDA-approved for major depressive disorder and seasonal affective disorder, with off-label use for smoking cessation and weight management in combination with naltrexone. 1
Primary Indications
FDA-Approved Uses
- Major Depressive Disorder (MDD): Bupropion is as effective as SSRIs and tricyclic antidepressants for treating MDD 2, 3
- Seasonal Affective Disorder (SAD): Approved for prevention and treatment 1
Off-Label Uses with Strong Evidence
Smoking Cessation: Bupropion 150 mg twice daily (maximum 300 mg/day) is highly effective 4, 5
- Start 1-2 weeks before quit date
- Days 1-3: 150 mg once daily
- Day 4 onward: 150 mg twice daily
- Duration: 7-12 weeks, may extend to 6-12 months 4
Weight Management: As naltrexone-bupropion ER combination for obesity 6
- Each tablet contains 8 mg naltrexone + 90 mg bupropion
- Titrate weekly to maintenance dose of 2 tablets twice daily
- Discontinue if <5% weight loss after 12 weeks at maintenance dose 6
Dosing Regimens
For Major Depressive Disorder
Immediate-Release (IR):
- Start: 100 mg twice daily
- Maximum: 450 mg/day in divided doses (three times daily)
- Avoid single doses >150 mg to reduce seizure risk 1, 2
Sustained-Release (SR):
- Start: 150 mg once daily in morning for 3 days
- Increase to 150 mg twice daily
- Maximum: 400 mg/day 5, 7, 1
Extended-Release (XL):
- Start: 150 mg once daily in morning
- May increase to 300 mg once daily after 4 days
- Maximum: 450 mg once daily 1, 2
Special Population Dosing
Hepatic Impairment:
- Moderate to severe: Maximum 150 mg every other day (XL) or 100 mg daily (IR/SR) 1
- For naltrexone-bupropion ER: Maximum 1 tablet daily 6
Renal Impairment:
- Moderate to severe (GFR <45 mL/min): Reduce dose by 50%
- End-stage renal disease: Maximum 150 mg every other day; avoid naltrexone-bupropion ER 6, 1
Geriatric: Start at lower end of dosing range due to decreased renal/hepatic function 1
Critical Contraindications
Absolute Contraindications
- Current seizure disorder or epilepsy
- History of seizures
- Conditions lowering seizure threshold:
- Brain metastases or stroke
- Anorexia nervosa or bulimia (current or prior)
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptics
- CNS tumor or arteriovenous malformation
Drug Interactions:
- MAO inhibitors: Must discontinue 14 days before starting bupropion 6, 1
- Concurrent use with other bupropion-containing products 1
Other Absolute Contraindications:
Relative Contraindications/Precautions
Cardiovascular:
- Uncontrolled hypertension: Monitor blood pressure closely; avoid naltrexone-bupropion ER 6
- Recent MI (<2 weeks), serious arrhythmias, or unstable angina: Use with caution 5
Opioid Use:
- For naltrexone-bupropion ER: Contraindicated with short-term or long-term opioid therapy
- Hold before procedures requiring opioids (e.g., endoscopy with fentanyl) 6
Psychiatric:
- Monitor for neuropsychiatric adverse effects, including suicidal ideation, especially in patients <24 years old 4, 6, 1
- The FDA removed the black box warning for neuropsychiatric events in smoking cessation, as large trials showed no increased risk compared to placebo 4
Drug Interactions Requiring Caution:
- Tamoxifen: Bupropion inhibits CYP2D6, potentially reducing tamoxifen efficacy 4
- Drugs metabolized by CYP2D6: Bupropion is a strong inhibitor 1
Clinical Pearls
Advantages Over Other Antidepressants
- Minimal sexual dysfunction: Lowest incidence among antidepressants 2, 3
- No weight gain: Unlike SSRIs and tricyclics; may promote weight loss 2, 3
- No somnolence: May actually cause insomnia 2, 3
- Dual benefit: Consider for patients with depression plus smoking or obesity 6
Common Adverse Effects
- Insomnia (dose in morning; avoid late-day dosing) 6, 5, 7
- Dry mouth 5, 7, 2
- Headache 7, 2
- Nausea 7, 2
- Agitation 8
Onset of Action
Discontinuation
- Taper dose gradually to minimize withdrawal symptoms 1
- No specific taper schedule mandated, but gradual reduction recommended