What are the guidelines for bupropion (Wellbutrin) management?

Bupropion Management Guidelines

Dosing and Administration

For major depressive disorder, initiate bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily) if tolerated, with a maximum dose of 400 mg/day for SR formulation or 450 mg/day for XL formulation. 1, 2

Standard Dosing by Indication

Major Depressive Disorder:

• Start with 150 mg once daily in the morning for 4 days 2
• Increase to target dose of 300 mg once daily (XL formulation) or 150 mg twice daily (SR formulation) 1, 2
• Maximum dose: 450 mg/day for XL, 400 mg/day for SR 1, 2
• Continue treatment for several months beyond acute response 2

Smoking Cessation:

• Begin dosing 1-2 weeks prior to target quit date 3, 1
• Days 1-3: 150 mg once daily 3
• Days 4 through 7-12 weeks: 150 mg twice daily (300 mg total) if tolerated 3
• Maximum dose: 300 mg/day for smoking cessation 3
• Treatment duration: 7-12 weeks, with possible extension to 6-12 months 3, 1

Seasonal Affective Disorder:

• Initiate in autumn before symptom onset 2
• Start with 150 mg once daily for 7 days 2
• Increase to 300 mg once daily if needed 2
• Continue through winter season, then taper in early spring 2

Dose Adjustments for Special Populations

Hepatic Impairment:

• Moderate to severe (Child-Pugh 7-15): Maximum 150 mg every other day 3, 1, 2
• Mild (Child-Pugh 5-6): Consider reducing dose and/or frequency 2

Renal Impairment:

• GFR <90 mL/min: Reduce total daily dose by half 3, 1, 2
• End-stage renal disease: Avoid use 3

Older Adults:

• Start with 37.5 mg every morning 1
• Increase by 37.5 mg every 3 days as tolerated 1
• Maximum: 150 mg twice daily (300 mg total) 1
• Administer second dose before 3 PM to minimize insomnia 1

Absolute Contraindications

Bupropion is contraindicated in patients with seizure disorders, current or prior bulimia/anorexia nervosa, abrupt discontinuation of alcohol/benzodiazepines/barbiturates/antiepileptics, concurrent MAOI use (or within 14 days), brain metastases, stroke history, uncontrolled hypertension, or hypersensitivity to bupropion. 3, 2

• Seizure disorders or conditions lowering seizure threshold 3, 2
• Current or prior diagnosis of bulimia or anorexia nervosa 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2
• Concurrent MAOI use or within 14 days of MAOI discontinuation 3, 2
• Brain metastases or stroke history 3, 4
• Uncontrolled hypertension 3
• Concurrent tamoxifen use 3
• Closed-angle glaucoma 3
• Concurrent opioid therapy (for naltrexone-bupropion combination) 3

Critical Monitoring Requirements

Monitor blood pressure and heart rate at baseline and periodically during treatment, especially in the first 12 weeks, and assess for neuropsychiatric adverse effects including suicidal ideation, particularly in patients under 24 years old. 3, 2

Neuropsychiatric Monitoring:

• Screen for suicidal thoughts and behaviors, especially in patients <24 years 2
• Monitor for worsening depression, mania/hypomania, psychosis, hallucinations, paranoia, delusions, aggression, hostility, agitation, anxiety, and panic 2
• Discontinue immediately if serious neuropsychiatric symptoms develop 3, 2
• Note: A large multicenter RCT (n=8,058) found no significant increase in neuropsychiatric adverse events with bupropion compared to nicotine patches or placebo in patients with or without psychiatric disorders 3

Cardiovascular Monitoring:

• Measure blood pressure and heart rate before initiating treatment 3
• Recheck periodically during treatment, especially first 12 weeks 3
• Avoid in patients with uncontrolled hypertension 3

Efficacy Assessment:

• For smoking cessation: Assess response at 7-12 weeks 1
• For weight management (naltrexone-bupropion): If <5% weight loss after 12 weeks on maintenance dose, discontinue as patient is likely a poor responder 3
• For depression: Assess response at 6-8 weeks; consider alternative treatment if no response 1

Clinical Considerations by Patient Population

For patients with comorbid depression and smoking cessation needs, bupropion is particularly beneficial as it addresses both conditions simultaneously, and when combined with naltrexone, it can mitigate weight gain associated with smoking cessation. 3, 1

Depression with Smoking Cessation:

• Bupropion addresses both conditions effectively 3, 1
• Naltrexone-bupropion combination reduces nicotine use and mitigates weight gain 3, 1

Depression with Migraine:

• Consider phentermine-topiramate ER as alternative (topiramate treats migraines) 3

Patients Requiring Opioid Therapy:

• Avoid naltrexone-bupropion combination 3
• Discontinue naltrexone-bupropion before procedures requiring opioids (e.g., endoscopy with fentanyl) 3

Cardiovascular Disease History:

• Avoid bupropion in patients with cardiovascular disease history 3
• Long-term cardiovascular safety of naltrexone-bupropion remains unclear (outcome trial terminated early) 3

Common Pitfalls and Safety Considerations

The most critical pitfall is exceeding 450 mg/day (XL) or 400 mg/day (SR), which significantly increases seizure risk; always use gradual dose titration and avoid in patients with any seizure risk factors. 1, 4, 2, 5

Seizure Risk Management:

• Seizure risk is dose-dependent: approximately 1 in 1,000 at therapeutic doses 4, 5
• Never exceed maximum doses: 450 mg/day (XL) or 400 mg/day (SR) 1, 2
• Use gradual titration to minimize risk 2
• Avoid in patients with any seizure predisposition 3, 4, 2

Drug Interactions:

• Do not use within 14 days of MAOI discontinuation (risk of hypertensive reactions) 3, 2
• Avoid with tamoxifen 3
• CYP2B6 inducers (ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, phenytoin) may require dose increase, but do not exceed maximum dose 2

Administration Considerations:

• Swallow tablets whole; do not crush, divide, or chew 2
• Administer in the morning to minimize insomnia 2
• Second dose (if applicable) should be taken before 3 PM 1
• May be taken with or without food 2

Discontinuation:

• For patients on 300 mg/day, taper to 150 mg once daily before discontinuing 2
• Gradual tapering reduces risk of withdrawal symptoms 2

Most Common Adverse Effects:

• Dry mouth, nausea, insomnia, dizziness, agitation, anxiety, tremor, headache 2, 6
• Weight loss (mean 0.5-1.0 kg) rather than weight gain seen with other antidepressants 7
• Minimal anticholinergic effects, orthostatic hypotension, cardiac conduction problems, and sexual dysfunction compared to TCAs and SSRIs 5, 8