What is the recommended dosing for Wellbutrin (Bupropion) SR for major depressive disorder?

Wellbutrin SR Dosing for Major Depressive Disorder

For Wellbutrin SR (bupropion sustained-release) in major depressive disorder, start with 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily dose) as the target maintenance dose. 1

Initial Dosing and Titration

• Start with 150 mg once daily in the morning for the first 3 days to assess tolerability and minimize seizure risk 1
• After 3 days, increase to 150 mg twice daily (300 mg total) if the medication is well tolerated 1
• The first dose should be taken in the morning and the second dose before 3 PM to minimize insomnia risk 1
• The maximum dose for bupropion SR is 400 mg per day (200 mg twice daily), though the standard therapeutic dose for MDD is 300 mg daily 1

Alternative Gradual Titration for Sensitive Patients

For patients who may be more sensitive to side effects (such as older adults or those on multiple medications):

• Start with 37.5 mg once daily in the morning 1
• Increase by 37.5 mg every 3 days as tolerated 1
• Target dose remains 150 mg twice daily (300 mg total) 1

Critical Timing Considerations

• Administer the first dose in the morning to leverage bupropion's activating properties 1
• Give the second dose before 3 PM to prevent insomnia, which is a common adverse effect 1
• This timing is particularly important in patients with sleep disturbances or those on multiple CNS-active medications 1

Monitoring Timeline

• Begin monitoring within 1-2 weeks of initiation for therapeutic response, adverse effects, and emergence of suicidal ideation, particularly in patients under 24 years old 2, 1
• Assess for adequate response at 6-8 weeks before considering treatment modification 2, 1
• The risk for suicide attempts is greatest during the first 1-2 months of treatment 2, 1
• If no adequate response occurs by 6-8 weeks at therapeutic doses, modify the treatment approach 2, 1

Special Population Dose Adjustments

Hepatic Impairment

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

Renal Impairment

• For GFR <90 mL/min: Reduce total daily dose by half 1
• Close monitoring for adverse reactions is required as bupropion and metabolites accumulate with renal impairment 1

Older Adults

• Start with 37.5 mg every morning, increase by 37.5 mg every 3 days 1
• Maximum dose: 150 mg twice daily (300 mg total) 1
• Lower starting doses minimize risk of adverse reactions in this population 1

Absolute Contraindications

• Seizure disorders or any condition that lowers seizure threshold 1, 3
• Current or recent (within 14 days) use of MAOIs 1, 3
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1
• Bulimia or anorexia nervosa due to increased seizure risk 1
• Uncontrolled hypertension 1

Discontinuation

• When discontinuing from 300 mg daily, taper to 150 mg once daily before stopping 1, 3
• This gradual taper minimizes withdrawal symptoms and seizure risk 3

Clinical Advantages

• Bupropion has lower rates of sexual dysfunction compared to SSRIs (fluoxetine, sertraline, paroxetine) 2
• May be particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia due to its activating properties 1
• Useful for patients with comorbid depression and smoking cessation goals, as it addresses both conditions 1
• Associated with weight loss rather than weight gain (mean 0.5-1.0 kg loss vs 0.2 kg with placebo) 4

Important Safety Monitoring

• Monitor blood pressure and heart rate periodically, especially during the first 12 weeks, as bupropion can cause elevations 1
• Black box warning for increased suicidal thoughts in patients under 24 years requires close monitoring 1
• Watch for agitation, irritability, or unusual behavioral changes as these may indicate worsening depression 2
• Be aware of historical bioequivalence issues between brand and generic formulations; monitor closely when switching 1