What is the usual adult starting dose of Wellbutrin (bupropion)?

Starting Dose for Wellbutrin (Bupropion)

For major depressive disorder, start Wellbutrin XL at 150 mg once daily in the morning, which can be increased to the usual target dose of 300 mg once daily after 4 days if tolerated. 1

Formulation-Specific Starting Doses

Wellbutrin XL (Extended-Release, Once Daily)

• Initial dose: 150 mg once daily in the morning 2, 1
• Target dose: 300 mg once daily after 4 days 2, 1
• Maximum dose: 450 mg once daily 2
• The XL formulation is the most commonly prescribed, with bupropion extended-release 24-hour 150 mg being the most frequent (62%) formulation at initiation 3

Wellbutrin SR (Sustained-Release, Twice Daily)

• Initial dose: 150 mg once daily for 3 days 2
• Target dose: 150 mg twice daily (300 mg total) starting on day 4 2
• Maximum dose: 400 mg per day (200 mg twice daily) 2
• The second dose must be given before 3 PM to minimize insomnia risk 2

Gradual Titration for Older Adults or High-Risk Patients

For older adults or patients requiring extra caution, start with 37.5 mg every morning and increase by 37.5 mg every 3 days as tolerated, targeting a maximum of 150 mg twice daily (300 mg total daily). 2

• This lower starting dose minimizes adverse reactions in vulnerable populations 2
• The gradual titration is critical to reduce seizure risk, which is dose-related 1

Dose Adjustments for Special Populations

Hepatic Impairment

• Moderate to severe hepatic impairment: 150 mg every other day (maximum dose) 2, 1
• Mild hepatic impairment: Consider reducing dose and/or frequency 2, 1

Renal Impairment

• Moderate to severe renal impairment (GFR <90 mL/min): Reduce total daily dose by 50% 2
• Consider reducing dose and/or frequency for any degree of renal impairment 1

Critical Safety Considerations Before Starting

Absolute Contraindications (Do Not Prescribe)

• Seizure disorder or any condition predisposing to seizures (history of head trauma, brain tumor, stroke) 2, 1
• Current or prior diagnosis of bulimia or anorexia nervosa 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1
• MAOI use within 14 days (or concurrent linezolid/IV methylene blue) 1
• Known hypersensitivity to bupropion 1

Relative Contraindications Requiring Extreme Caution

• Uncontrolled hypertension – bupropion elevates blood pressure and heart rate 2, 4
• Concurrent tamoxifen therapy (bupropion inhibits CYP2D6) 2
• Untreated narrow-angle glaucoma 1

Monitoring During Initiation

First 1-2 Weeks

• Assess for suicidal ideation, agitation, irritability, or behavioral changes – highest risk period for suicide attempts, especially in patients <24 years old 2, 1
• Monitor for early signs of serotonin syndrome if combining with other serotonergic agents: confusion, tremor, clonus, hypertension, tachycardia, sweating 2

First 12 Weeks

• Monitor blood pressure and heart rate periodically – bupropion can cause elevations in both parameters 2, 4

6-8 Weeks

• Assess for adequate therapeutic response – if no response by 6-8 weeks at therapeutic doses, modify treatment (increase dose, switch, or augment) 2

Common Pitfalls to Avoid

• Never exceed 450 mg/day – seizure risk increases significantly above this dose (approximately 0.1% at ≤300 mg/day for smoking cessation, higher at excessive doses) 2, 5
• Do not dose the SR formulation late in the day – the second dose must be before 3 PM to prevent insomnia 2
• Do not start at full therapeutic dose – gradual titration over 3-4 days minimizes seizure risk and improves tolerability 1
• Do not prescribe to patients with eating disorders – even if currently in remission, this remains an absolute contraindication due to seizure risk 2, 1

Clinical Advantages of Bupropion

• Lower rates of sexual dysfunction compared to SSRIs 2
• Minimal weight gain or weight loss unlike many other antidepressants 2
• Activating properties beneficial for patients with low energy, apathy, or hypersomnia 2
• Dual benefit for depression and smoking cessation 2