What is the recommended dosing for Wellbutrin (bupropion)?

Wellbutrin (Bupropion) Dosing

For depression, start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily); for smoking cessation, use the same titration schedule beginning 1-2 weeks before the quit date, with treatment lasting 7-12 weeks. 1, 2

Standard Dosing by Indication

Major Depressive Disorder

• Initial dose: 150 mg once daily for 3 days 2
• Maintenance dose: 150 mg twice daily (300 mg total daily) for SR formulation 2
• XL formulation: Start 150 mg once daily, increase to 300 mg once daily as maintenance 2
• Maximum dose: 400 mg/day for SR; 450 mg/day for XL 2, 3
• The FDA-approved effective dose range is 300-450 mg/day, with the 450 mg dose showing superior efficacy in controlled trials 3

Smoking Cessation

• Initiation timing: Begin 1-2 weeks before target quit date to establish therapeutic drug levels 1, 2
• Days 1-3: 150 mg once daily 1, 2
• Days 4 through end of treatment: 150 mg twice daily (300 mg total) if tolerated 1, 2
• Maximum dose: 300 mg/day for smoking cessation 1, 2
• Treatment duration: 7-12 weeks, with efficacy assessed at completion 1, 2
• Therapy may be extended to 6 months-1 year to promote continued cessation 1

Timing of Administration

Take the first dose in the morning and the second dose (for SR formulation) before 3 PM to minimize insomnia risk. 2, 4

• Morning dosing leverages bupropion's activating properties 2
• Late-day dosing significantly increases insomnia risk, the most common side effect 2, 4, 5
• XL formulation should be taken once daily in the morning only 2

Special Population Dosing

Older Adults (≥55 years)

• Initial dose: 37.5 mg once daily in the morning 2, 4
• Titration: Increase by 37.5 mg every 3 days as tolerated 2, 4
• Maximum dose: 150 mg twice daily (300 mg total daily) 2, 4
• Lower starting doses minimize adverse reactions in this population 2

Renal Impairment (GFR <90 mL/min)

• Reduce total daily dose by half 2, 4
• Bupropion and metabolites accumulate with renal dysfunction, requiring close monitoring for adverse reactions 2, 4, 3

Hepatic Impairment

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

Critical Safety Considerations

Absolute Contraindications

• Seizure disorders or conditions lowering seizure threshold (stroke, brain metastases, eating disorders) 1, 2
• Concurrent MAOI use or within 14 days of discontinuing MAOIs 1, 2
• Bulimia or anorexia nervosa due to increased seizure risk 2, 4

Seizure Risk Minimization

• Never exceed 300 mg/day for smoking cessation or 450 mg/day for depression 1, 2, 3
• The seizure incidence is approximately 0.1% when dosing guidelines are followed 5, 6
• Gradual titration is essential to minimize seizure risk while achieving therapeutic levels 2

Monitoring Requirements

• Neuropsychiatric symptoms: Monitor for suicidal ideation (especially in patients <24 years), agitation, anxiety, mood changes 1, 4, 3
• Blood pressure: Check at baseline and during titration; avoid in uncontrolled hypertension 2, 4
• Drug interactions: Use caution with CYP2D6 inhibitors and avoid concurrent tamoxifen (reduces tamoxifen efficacy) 2, 4

Common Side Effects and Management

• Insomnia (most common): Managed by ensuring second dose is before 3 PM 2, 4, 5
• Dry mouth: Generally transient and resolves without intervention 5, 6
• Nausea, headache, anxiety: Occur more frequently than placebo but are typically mild 5
• Most side effects are transient and can be managed by dose reduction if necessary 5
• Discontinuation rates due to adverse events are low (6-12%) in clinical trials 5

Clinical Pearls

• Bupropion may be particularly beneficial for patients with comorbid depression and desire to quit smoking, addressing both conditions simultaneously 1, 2
• The activating properties make it useful for patients with depression accompanied by apathy or low energy 2
• If no response after 6-8 weeks at adequate dose, consider alternative treatment 2
• Bupropion can be safely combined with NRT for smoking cessation with appropriate monitoring 1