What is the recommended dosing regimen for Bupropion (Wellbutrin) SR?

Bupropion SR Dosing Regimen

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 administered before 3 PM to minimize insomnia risk. 1

Standard Dosing for Major Depressive Disorder

• Initial dose: 150 mg once daily in the morning for the first 3 days 1
• Maintenance dose: 150 mg twice daily (300 mg total daily) starting on day 4 1
• Maximum dose: 400 mg per day for the SR formulation 1
• Critical timing: The second daily dose must be taken before 3 PM to prevent insomnia, which is the most common side effect 1, 2

Dosing for Smoking Cessation

• Standard regimen: 150 mg twice daily (300 mg total) of the SR formulation 1
• Initiation timing: Begin treatment 1-2 weeks before the target quit date to establish therapeutic drug levels 1
• Treatment duration: Typically 7-12 weeks, with efficacy assessed after this period 1
• This indication may be particularly beneficial for patients with comorbid depression who want to quit smoking 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 daily) 1, 2
• This conservative approach minimizes risk of adverse reactions in older adults 1

Hepatic Impairment

• Moderate to severe impairment (Child-Pugh 7-15): Maximum 150 mg daily (one tablet only), or 150 mg every other day per FDA labeling 1, 3
• Mild impairment (Child-Pugh 5-6): Consider reducing dose and/or frequency 3

Renal Impairment

• GFR <90 mL/min: Reduce total daily dose by half and/or reduce frequency 1, 2
• Bupropion and its metabolites are cleared renally and may accumulate, requiring close monitoring 1, 2

Critical Safety Considerations and Contraindications

Absolute Contraindications

• Seizure disorders: Bupropion lowers the seizure threshold and should be avoided entirely 1, 2
• Eating disorders: Patients with bulimia or anorexia nervosa have increased seizure risk and should not receive bupropion 1, 2
• MAOI use: Avoid within 14 days of discontinuing MAOIs due to hypertensive reaction risk 1, 3
• Abrupt withdrawal states: Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs is an absolute contraindication 1

Relative Contraindications and Warnings

• Uncontrolled hypertension: Requires close blood pressure monitoring throughout treatment 1, 2
• Tamoxifen use: Concurrent use may reduce tamoxifen efficacy through CYP2D6 inhibition 1, 2
• Maximum dose limit: Do not exceed 450 mg per day to minimize seizure risk 1

Monitoring Requirements

• Neuropsychiatric symptoms: Monitor for suicidal ideation, especially in patients <24 years old, and assess for agitation, anxiety, and mood changes 1, 2
• Blood pressure: Check at baseline and during titration 2
• Treatment response: Allow 6-8 weeks at an adequate dose before determining efficacy; if no response, consider alternative treatment 1
• Energy levels: Bupropion may produce more rapid improvement in energy levels compared to other antidepressants, sometimes within the first few weeks 1

Formulation-Specific Considerations

• SR formulation: Administered twice daily, provides steady drug levels throughout the day 1
• Do not crush or divide: Tablets must be swallowed whole to maintain sustained-release properties 3
• Bioequivalence concerns: Monitor patients closely when switching between brand and generic formulations, as historical bioequivalence issues have been documented 1

Discontinuation Protocol

• For patients on 300 mg daily: Taper to 150 mg once daily before complete discontinuation 1, 3
• Gradual tapering minimizes withdrawal symptoms and allows for monitoring of depressive symptom recurrence 3

Clinical Advantages

• Lower sexual dysfunction: Compared to SSRIs, bupropion has significantly lower rates of sexual side effects 1
• Weight neutral: Less likely to cause weight gain compared to many other antidepressants 1
• Activating properties: Particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia 1
• Dual indication: Can address both depression and smoking cessation simultaneously 1