What is the recommended dosing for Welbutrin (bupropion) in the treatment of Major Depressive Disorder (MDD)?

Wellbutrin (Bupropion) Dosing for Major Depressive Disorder

For MDD, start bupropion XL at 150 mg once daily in the morning, then increase to the target dose of 300 mg once daily after 4 days if tolerated. 1

Standard Dosing Regimen

Bupropion XL (Extended-Release) - Preferred Formulation

• Initial dose: 150 mg once daily in the morning 1
• Titration: After 4 days, increase to 300 mg once daily in the morning 1
• Maximum dose: 450 mg once daily (though doses above 300 mg were not extensively studied for MDD) 2, 1
• Administration: Take in the morning with or without food; swallow whole—do not crush, divide, or chew 1

Bupropion SR (Sustained-Release) - Alternative Formulation

• Initial dose: 150 mg once daily for 3 days 2
• Target dose: 150 mg twice daily (300 mg total daily) 2
• Maximum dose: 400 mg per day 2
• Timing: First dose in the morning, second dose before 3 PM to minimize insomnia risk 2

Special Population Adjustments

Older Adults

• Start low: 37.5 mg once daily in the morning 2
• Titration: Increase by 37.5 mg every 3 days as tolerated 2
• Maximum dose: 150 mg twice daily (300 mg total daily) 2
• Lower starting doses are necessary due to increased risk of adverse reactions in this population 2

Hepatic Impairment

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

Renal Impairment

• GFR <90 mL/min: Reduce total daily dose by half 2, 1
• Bupropion and metabolites are cleared renally and may accumulate 2

Critical Safety Considerations

Absolute Contraindications

• Seizure disorders or conditions lowering seizure threshold 2, 1
• Eating disorders (bulimia, anorexia nervosa): Increased seizure risk 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2
• Current MAOI use or within 14 days of MAOI discontinuation 1
• Uncontrolled hypertension 2

Seizure Risk Minimization

• The maximum dose should not exceed 450 mg per day to minimize seizure risk 2
• Gradual dose titration is essential 1
• Do not crush, divide, or chew extended-release formulations 1

Monitoring and Efficacy Assessment

Timeline for Response

• Allow 6-8 weeks at adequate dose before determining treatment response 2
• Energy levels may improve more rapidly, sometimes within the first few weeks 2
• If no response after 6-8 weeks at adequate dose, consider alternative treatment 2

Required Monitoring

• Blood pressure: Monitor regularly, especially in patients with hypertension 2
• Neuropsychiatric symptoms: Particularly in patients younger than 24 years 2
• Agitation: Bupropion has activating properties that may increase agitation 2

Clinical Advantages and Considerations

Favorable Side Effect Profile

• Lower rates of sexual dysfunction compared to SSRIs like fluoxetine, sertraline, and escitalopram 3, 4, 5
• Less somnolence compared to tricyclic antidepressants and some SSRIs 4, 5
• Minimal weight gain compared to other antidepressants 4, 5

Ideal Patient Characteristics

• Depression with low energy, apathy, or hypersomnia: Bupropion's activating properties are particularly beneficial 2, 6
• Comorbid smoking cessation needs: Addresses both conditions simultaneously 2
• Patients concerned about sexual dysfunction or weight gain 3, 4, 5

Formulation Switching

When Switching Between Formulations

• Give the same total daily dose when possible when switching from immediate-release or SR to XL 1
• Monitor closely for loss of antidepressant effect, as historical bioequivalence issues have been reported with some generic formulations 2

Discontinuation Protocol

Tapering Strategy

• For patients on 300 mg daily: Decrease to 150 mg once daily before discontinuation 1
• Gradual tapering minimizes withdrawal symptoms 1

Common Pitfalls to Avoid

• Late-day dosing: Always administer second SR dose before 3 PM to prevent insomnia 2
• Crushing tablets: Never crush, divide, or chew extended-release formulations—this increases seizure risk 1
• Inadequate trial duration: Must allow full 6-8 weeks at therapeutic dose before declaring treatment failure 2
• Ignoring renal/hepatic function: Always adjust doses in impaired patients to prevent accumulation 2, 1
• Generic substitution without monitoring: Be aware of potential bioequivalence issues when switching formulations 2