What is the appropriate starting dose of bupropion (Wellbutrin) for an adult with major depressive disorder and anxiety, assuming no contraindications?

Starting Dose for Wellbutrin in Major Depressive Disorder with Anxiety

For an adult with major depressive disorder and comorbid anxiety, start bupropion XL at 150 mg once daily in the morning, then increase to 300 mg once daily after 4 days if tolerated. 1

Initial Dosing Protocol

• Begin with 150 mg once daily in the morning for the first 4 days to minimize seizure risk and assess tolerability 1
• Increase to the target dose of 300 mg once daily after the initial 4-day period 1
• Administer in the morning and may be taken with or without food 1
• Swallow tablets whole—do not crush, divide, or chew 1

Critical Pre-Treatment Screening

Before prescribing bupropion, you must screen for absolute contraindications 2:

• Seizure disorders or any condition predisposing to seizures (history of head trauma, brain tumor, stroke) 2, 1
• Current or recent MAOI use (within 14 days) 2, 1
• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk 2
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 2
• Uncontrolled hypertension 2
• Moderate to severe hepatic or renal impairment requiring dose adjustment 2, 1

Anxiety Considerations

The presence of comorbid anxiety does not significantly affect bupropion's efficacy based on STAR*D trial analyses 2. However, be aware that:

• Bupropion has activating properties that may initially increase anxiety or agitation in some patients 2
• SSRIs are generally preferred first-line for anxious depression, but bupropion remains safe and effective in this population 2
• Monitor closely for increased agitation during the first 1-2 weeks 2

Monitoring Requirements

First 1-2 Weeks (Critical Period)

• Assess for suicidal ideation, agitation, irritability, or unusual behavioral changes—the risk of suicide attempts is highest during the first 1-2 months, particularly in patients under 24 years 2, 1
• Monitor for early signs of tolerability issues (insomnia, anxiety, dry mouth) 2
• Check blood pressure and heart rate as bupropion can elevate both parameters 2

Weeks 2-8

• Continue monitoring therapeutic response and adverse effects 2
• Allow 6-8 weeks at an adequate dose before determining treatment response 2
• Energy levels may improve within the first few weeks, but full antidepressant effect requires 4-6 weeks 3, 4

Dose Adjustments for Special Populations

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 50% 2
• Monitor closely for adverse reactions as bupropion metabolites accumulate 2

Older Adults

• Start with 37.5 mg every morning, increase by 37.5 mg every 3 days as tolerated 2
• Maximum dose: 150 mg twice daily (300 mg total) 2

Maximum Dosing and Safety

• Maximum dose for MDD is 450 mg/day (XL formulation) to maintain seizure risk at approximately 0.1% 2, 1
• The seizure risk at therapeutic doses (300 mg/day) is approximately 1 in 1,000 2
• Never exceed maximum doses—higher doses substantially increase seizure risk 2

Clinical Advantages in This Population

• Significantly lower rates of sexual dysfunction compared to SSRIs 2, 5
• Minimal weight gain or even weight loss, unlike many other antidepressants 2
• Lower rates of sedation than SSRIs 2
• Particularly beneficial for patients with low energy, apathy, or hypersomnia due to activating properties 2, 4

Common Pitfalls to Avoid

• Do not start at 300 mg—gradual titration is essential to minimize seizure risk 1
• Do not discontinue prematurely before 6-8 weeks unless significant adverse effects occur 2
• Do not assume generic formulations are equivalent—historical bioequivalence issues require close monitoring when switching formulations 2, 6
• Do not give late-day doses if using SR formulation—second dose must be before 3 PM to minimize insomnia 2

When to Modify Treatment

If no adequate response occurs by 6-8 weeks at 300 mg daily 2:

• Consider increasing to 450 mg once daily (maximum dose) 1
• Consider augmentation with an SSRI rather than switching 2
• Bupropion augmentation of SSRIs shows superior efficacy compared to other augmentation strategies 2