What is the starting dose of Wellbutrin (bupropion) for adults with depression?

Starting Dose of Wellbutrin for Depression

For adults with major depressive disorder, start Wellbutrin SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily dose). 1

Standard Dosing by Formulation

Wellbutrin SR (Sustained Release)

• Initial dose: 150 mg once daily 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 1
• Timing: Take the first dose in the morning and the second dose before 3 PM to minimize insomnia risk 1

Wellbutrin XL (Extended Release)

• Initial dose: 150 mg once daily for 1 week 2
• Maintenance dose: 300 mg once daily 2
• Maximum dose: 450 mg per day 1
• Timing: Administer in the morning 1

The FDA label confirms that clinical trials established efficacy at 300 mg per day for most patients, though some trials demonstrated efficacy only at 450 mg per day 2. The 300 mg daily dose represents the standard therapeutic target for major depressive disorder 1, 2.

Special Population Dosing Adjustments

Older Adults (≥60 years)

• Initial dose: 37.5 mg once daily in the morning 1
• Titration: Increase by 37.5 mg every 3 days as tolerated 1
• Target dose: 150 mg twice daily (300 mg total daily) 1
• Maximum dose: 300 mg per day 1

This lower starting dose minimizes adverse reactions in older adults who have increased sensitivity to medication effects 1.

Hepatic Impairment

• Moderate to severe impairment: Maximum 150 mg daily (one tablet total) 1
• Bupropion and its metabolites accumulate significantly in hepatic dysfunction, requiring substantial dose reduction 1

Renal Impairment

• GFR <90 mL/min: Reduce total daily dose by 50% 1
• Bupropion metabolites are cleared renally and accumulate in renal dysfunction, requiring close monitoring 1

Critical Safety Considerations

Absolute Contraindications

• Seizure disorders: Bupropion lowers seizure threshold (risk approximately 1 in 1,000 at standard doses) 1
• Eating disorders: Bulimia or anorexia nervosa significantly increase seizure risk 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs: Dramatically increases seizure risk 1
• MAOI use: Avoid within 14 days of MAOI discontinuation 1
• Uncontrolled hypertension: Bupropion can elevate blood pressure and heart rate 1

Maximum Dosing to Minimize Seizure Risk

• Never exceed 450 mg per day for any indication 1
• For smoking cessation specifically, maximum dose is 300 mg per day 1

Monitoring and Response Assessment

Early Monitoring (Weeks 1-2)

• Monitor for worsening depression, suicidal ideation, or behavioral changes, particularly in patients under 24 years old 1
• The FDA black box warning emphasizes increased suicide risk in young adults during the first 1-2 months of treatment 1
• Assess for neuropsychiatric adverse effects including agitation, anxiety, panic attacks, insomnia, irritability, hostility, and akathisia 1
• Monitor blood pressure and heart rate, especially during the first 12 weeks 1

Efficacy Assessment (Weeks 6-8)

• Allow 6-8 weeks at therapeutic doses before determining treatment response 1
• If no adequate response occurs by 6-8 weeks, modify the treatment approach 1
• Bupropion may produce more rapid improvement in energy levels compared to other antidepressants, sometimes within the first few weeks 1

Response rates to antidepressant therapy are approximately 50%, with 38% of patients not achieving treatment response and 54% not achieving remission during 6-12 weeks of treatment 1.

Clinical Advantages and Patient Selection

Bupropion is particularly beneficial for specific patient populations:

• Patients with low energy, apathy, or hypersomnia due to its activating properties 1
• Patients concerned about sexual dysfunction (lower rates compared to SSRIs) 1
• Patients concerned about weight gain (associated with weight loss rather than gain) 1, 3
• Patients who also want to quit smoking (addresses both depression and nicotine dependence) 1

Common Pitfalls to Avoid

• Do not administer the second SR dose after 3 PM: This increases insomnia risk due to bupropion's activating properties 1
• Do not discontinue prematurely before 6-8 weeks: Unless significant adverse effects occur, allow adequate time for therapeutic response 1
• Monitor closely when switching between brand and generic formulations: Historical bioequivalence issues have been documented, potentially leading to loss of antidepressant effect 1
• Do not combine with tamoxifen: Bupropion is contraindicated in patients taking tamoxifen 1