What is the recommended dosage and use of Bupropion (Wellbutrin) for treating major depressive disorder and smoking cessation?

Bupropion Dosing and Administration

Major Depressive Disorder

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) as the maintenance dose. 1

Standard Dosing Protocol

• Initial dose: 150 mg once daily in the morning 1, 2
• Titration: After 4 days, increase to 300 mg once daily (for XL formulation) or 150 mg twice daily (for SR formulation) 2, 1
• Maximum dose: 450 mg/day for XL formulation; 400 mg/day for SR formulation 1
• Second dose timing: When using SR formulation, administer the second dose before 3 PM to minimize insomnia risk 1

Formulation Differences

• Bupropion SR: 150 mg twice daily (total 300 mg/day) provides more flexible dosing 1
• Bupropion XL: 300 mg once daily in the morning offers simplified administration 1, 2
• Both formulations are bioequivalent in terms of systemic bupropion exposure 3

Response Assessment

• Allow 6-8 weeks at an adequate dose before determining treatment response 1
• Energy levels may improve more rapidly, sometimes within the first few weeks 1
• If no response after 6-8 weeks at adequate dose, consider alternative treatment 1

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Smoking Cessation

For smoking cessation, initiate bupropion SR 1-2 weeks before the target quit date at 150 mg once daily for days 1-3, then increase to 150 mg twice daily (300 mg total) for 7-12 weeks. 4

Standard Dosing Protocol

• Pre-quit initiation: Begin 1-2 weeks prior to target quit date to establish therapeutic drug levels 4, 1
• Days 1-3: 150 mg orally once daily 4
• Day 4 through week 12: 150 mg orally twice daily if tolerated 4
• Maximum dose: 300 mg per day for smoking cessation 4

Treatment Duration

• Standard duration is 7-12 weeks 4, 1
• Therapy may be extended to 6 months to 1 year to promote continued cessation while attempting to avoid longer periods if possible 4
• Assess efficacy formally after 7-12 weeks of treatment 1

Combination Therapy

• Bupropion may be combined with nicotine replacement therapy (NRT) for enhanced efficacy 4
• Particularly beneficial for patients with comorbid depression who want to quit smoking, addressing both conditions simultaneously 1

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Special Population Dosing

Older Adults

For older adults, start with 37.5 mg every morning and gradually increase by 37.5 mg every 3 days as tolerated, with a maximum dose of 150 mg twice daily (300 mg total). 1

• Lower starting doses (approximately 50% of standard dose) are appropriate due to increased risk of adverse reactions 1
• Administer second dose before 3 PM to prevent sleep disturbances 1

Hepatic Impairment

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

Renal Impairment

• Moderate to severe renal impairment (GFR <90 mL/min): Reduce total daily dose by half 1
• Bupropion and metabolites are cleared renally and may accumulate, requiring close monitoring 1

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Critical Safety Considerations

Absolute Contraindications

• Seizure disorders: Bupropion lowers seizure threshold and is contraindicated 4, 2
• Current or prior bulimia or anorexia nervosa: Increased seizure risk 2, 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs: Increased seizure risk 2, 1
• MAOIs: Do not use within 14 days of stopping MAOIs or starting bupropion 2, 4
• Brain metastases or stroke: Contraindicated due to seizure risk 4
• Closed-angle glaucoma: Contraindicated 4
• Concurrent tamoxifen use: Contraindicated 4

Seizure Risk Minimization

• The maximum dose of 450 mg/day should not be exceeded to minimize seizure risk 1, 2
• Gradual dose titration is necessary to minimize seizure risk while achieving therapeutic levels 1
• Discontinue immediately if seizure occurs 2

Neuropsychiatric Monitoring

• Monitor for development or worsening of depression, suicidal ideation/behavior, hostility, agitation, or psychosis 4, 2
• This applies to patients with and without previous psychiatric history 4
• A large multicenter RCT found that neuropsychiatric adverse event rates with bupropion were not significantly increased relative to nicotine patches or placebo in patients with or without psychiatric disorders 4
• Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants requires close monitoring 2

Cardiovascular Monitoring

• Monitor blood pressure before initiating treatment and periodically during treatment 2
• Avoid in patients with uncontrolled hypertension 1

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Clinical Pearls

Optimal Patient Selection

• Bupropion may be particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia due to its activating properties 1
• Effective for patients who want to quit smoking while managing depression 1
• May improve SSRI-associated sexual dysfunction when added to SSRI therapy 5

Formulation Selection

• Choose SR formulation for patients requiring more flexible dosing due to side effects or need for dose adjustments in hepatic/renal impairment 1
• Monitor closely when switching between brand and generic formulations or between SR and XL formulations due to historical bioequivalence issues 1

Common Side Effects

• Most common adverse reactions (≥5%; ≥2× placebo): dry mouth, nausea, insomnia, dizziness, agitation, anxiety, tremor 2
• Minimal weight gain compared to other antidepressants 5
• Less somnolence and sexual dysfunction compared to SSRIs 3