What is the recommended dosing for Wellbutrin (bupropion)?

Wellbutrin (Bupropion) Dosing

For major depressive disorder, start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily dose), with the second dose taken before 3 PM to minimize insomnia risk. 1, 2

Standard Dosing by Formulation

Bupropion SR (Sustained Release)

• Initial dose: 150 mg once daily in the morning for days 1-3 1, 2
• Maintenance dose: 150 mg twice daily (300 mg total) starting day 4 1, 2
• Maximum dose: 400 mg per day 1, 2
• Critical timing: Second dose must be administered before 3 PM to prevent insomnia 1, 2

Bupropion XL (Extended Release)

• Initial dose: 150 mg once daily in the morning for 1 week 1
• Maintenance dose: 300 mg once daily 1
• Maximum dose: 450 mg per day 1, 2, 3
• Administration: Single morning dose 1

Indication-Specific Dosing

Smoking Cessation

• Dosing schedule: 150 mg once daily for days 1-3, then 150 mg twice daily (300 mg total) 1, 2
• Maximum dose: 300 mg per day for smoking cessation 1, 2
• Timing: Begin 1-2 weeks before target quit date 1, 2
• Duration: 7-12 weeks standard treatment, with possible extension to 6 months-1 year 1, 2
• Efficacy assessment: Evaluate response after 7-12 weeks 1

Special Population Adjustments

Older Adults (≥55 years)

• Initial dose: 37.5 mg once daily in the morning 1, 2
• Titration: Increase by 37.5 mg every 3 days as tolerated 1, 2
• Maximum dose: 150 mg twice daily (300 mg total) 1, 2
• Rationale: Approximately 50% of standard adult starting doses due to increased risk of adverse reactions 2

Hepatic Impairment

• Moderate to severe impairment: Maximum dose 150 mg daily (one tablet) 1, 2

Renal Impairment

• GFR <90 mL/min: Reduce total daily dose by half 1, 2
• Monitoring: Close surveillance for adverse reactions due to drug accumulation 1

Critical Safety Considerations and Contraindications

Absolute Contraindications

• Seizure disorders or conditions lowering seizure threshold 1, 2
• Brain metastases (due to seizure risk) 2
• Concurrent MAOI use or within 14 days of discontinuing MAOIs 1, 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1, 2
• Patients with bulimia or anorexia nervosa (increased seizure risk) 1

Seizure Risk Management

• Maximum dose limit: Must not exceed 450 mg per day to minimize seizure risk 1, 2
• Seizure incidence: Approximately 0.4% at doses up to 450 mg/day 2
• Dose-dependent risk: Gradual titration is necessary to minimize seizure risk while achieving therapeutic levels 1

Monitoring Requirements

• Neuropsychiatric symptoms: Monitor for depression worsening, suicidal ideation, agitation, anxiety, and mood changes, especially in patients <24 years 1, 2
• Blood pressure: Check at baseline and during titration, as bupropion can cause elevations 1, 2
• Uncontrolled hypertension: Requires close blood pressure monitoring 2
• Early monitoring: Begin within 1-2 weeks of initiation for therapeutic response and adverse effects 1
• Suicide risk: Greatest during first 1-2 months of treatment 1

Efficacy Assessment Timeline

• Initial monitoring: Within 1-2 weeks of initiation 1
• Adequate trial duration: Allow 6-8 weeks at therapeutic dose before determining treatment response 1, 2
• Energy improvement: May occur more rapidly, sometimes within first few weeks 1
• Treatment modification: If no adequate response by 6-8 weeks at therapeutic doses, modify treatment approach 1

Clinical Advantages

Favorable Side Effect Profile

• Lower rates of sexual dysfunction compared to SSRIs 1, 4, 5
• Less somnolence than TCAs and SSRIs 4, 5
• Potential for weight loss rather than weight gain 2

Ideal Patient Populations

• Depression with low energy, apathy, or hypersomnia (due to activating properties) 1, 2
• Patients concerned about sexual dysfunction or weight gain 1
• Comorbid depression and smoking cessation (addresses both conditions simultaneously) 1

Common Side Effects

• Most common: Insomnia (manageable by proper timing of doses), agitation, dry mouth, nausea, headache, and tremor 2

Important Clinical Pearls

Formulation Switching

• Monitor closely when switching between brand and generic formulations or between SR and XL formulations due to historical bioequivalence issues that may lead to loss of antidepressant effect 1

Drug Interactions

• Naltrexone-bupropion combination: Confirm patient is not currently taking opioid medications before initiating 1
• Tamoxifen: Bupropion is contraindicated in patients taking tamoxifen 1

Maintenance Treatment

• Long-term efficacy: Patients on bupropion 300 mg per day experienced significantly lower relapse rates over 44 weeks compared to placebo 3
• Median time to relapse: 44 weeks with bupropion treatment 6