What is the recommended dosing for Wellbutrin (bupropion)?

Wellbutrin (Bupropion) Dosing

For smoking cessation, start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily) if tolerated, beginning 1-2 weeks before the target quit date and continuing for 7-12 weeks. 1, 2

Smoking Cessation Dosing

Standard Titration Schedule:

• Days 1-3: 150 mg orally once daily 1, 2
• Day 4 through 7-12 weeks: 150 mg orally twice daily (300 mg total daily dose) if tolerated 1, 2
• Maximum dose: 300 mg per day for smoking cessation 1, 2

Critical Timing:

• Begin dosing 1-2 weeks prior to the target quit date to establish therapeutic drug levels before cessation attempts 1, 2
• Treatment duration is typically 7-12 weeks, with efficacy formally assessed after this period 1, 2
• Therapy may be extended to promote continued cessation (6 months to 1 year) while attempting to avoid longer periods if possible 1

Major Depressive Disorder Dosing

Bupropion SR (Sustained Release):

• Initial dose: 100-150 mg once daily for 3 days 2
• Maintenance dose: 150 mg twice daily (300 mg total daily) 2
• Maximum dose: 400 mg per day 2

Bupropion XL (Extended Release):

• Initial dose: 150 mg once daily 2
• Maintenance dose: 150-300 mg once daily 2
• Maximum dose: 450 mg per day 2, 3
• The FDA label indicates that 450 mg per day demonstrated efficacy in clinical trials, though 300 mg per day was also effective 3

Administration timing: To minimize insomnia risk, administer the second dose of SR formulation before 3 p.m. 2

Special Population Dose Adjustments

Older Adults:

• Start with 37.5 mg every morning, then gradually increase by 37.5 mg every 3 days as tolerated to minimize adverse reactions 2
• Maximum dose: 150 mg twice daily (300 mg total daily) 2

Hepatic Impairment (Moderate to Severe):

• Total daily dose should not exceed 150 mg daily (one tablet) 2

Renal Impairment (Moderate to Severe, GFR <90 mL/min):

• Reduce total daily dose by half, as bupropion and metabolites are cleared renally and may accumulate 2
• Close monitoring for adverse reactions is required 2

Absolute Contraindications

Do not use bupropion in patients with:

• Seizure disorders or conditions that lower seizure threshold (stroke, brain metastases) 1, 2
• Current use of MAO inhibitors or within 14 days of discontinuing MAOIs (increased risk of hypertensive reactions) 1, 2
• Bulimia or anorexia nervosa (increased seizure risk) 2
• Concurrent tamoxifen use 2
• Closed-angle glaucoma 1

Safety Monitoring and Common Pitfalls

Seizure Risk Minimization:

• The maximum dose of 450 mg per day (for XL formulation) or 400 mg per day (for SR formulation) must not be exceeded to keep seizure risk at approximately 0.1% 2, 4
• Gradual titration is necessary to minimize seizure risk while achieving therapeutic levels 2
• Screen all patients for predisposing risk factors before initiating therapy 4

Neuropsychiatric Monitoring:

• Monitor for development or worsening of depression, suicidal ideation/behavior, hostility, agitation, and anxiety, especially in patients younger than 24 years 2, 3
• These side effects are uncommon but require discontinuation if they occur 1
• A large multicenter RCT found that neuropsychiatric adverse events with bupropion were not significantly increased relative to nicotine patches or placebo in patients with or without psychiatric disorders 1

Common Adverse Effects:

• Insomnia and dry mouth occur significantly more frequently than placebo but are generally transient and often resolve without intervention 4
• Nausea is common and may need management, especially during chemotherapy in cancer patients 1
• Most adverse effects can be managed by dose reduction if necessary 4

Blood Pressure Monitoring:

• Monitor vital signs, particularly blood pressure, as bupropion should be avoided in patients with uncontrolled hypertension 2

Clinical Pearls

• Bupropion may be particularly beneficial for patients with comorbid depression who want to quit smoking, addressing both conditions simultaneously 2
• Combining bupropion with naltrexone can help with smoking cessation while mitigating associated weight gain 2
• Bupropion can be safely combined with nicotine replacement therapy (NRT) with appropriate monitoring 1, 4
• If no response is seen after 6-8 weeks at an adequate dose for depression, consider alternative treatment 2
• The onset of action for depression is 2 weeks with full efficacy attained at 4 weeks of treatment 5