What is the recommended starting dose for Wellbutrin (bupropion) in adults with major depressive disorder?

Starting Dose for Wellbutrin (Bupropion)

For major depressive disorder in adults, start Wellbutrin 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 Protocol

The FDA-approved dosing for bupropion XL (extended-release) follows a straightforward titration schedule 1:

• Days 1-4: 150 mg once daily in the morning
• Day 5 onward: Increase to 300 mg once daily in the morning (target dose)

For bupropion SR (sustained-release), the American Family Physician recommends starting with 150 mg once daily for 3 days, then increasing to 150 mg twice daily 2. The second dose of SR formulation must be administered before 3 PM to minimize insomnia risk 2.

Formulation-Specific Considerations

The XL formulation offers the advantage of once-daily dosing, which improves adherence and tolerability. 1 All three formulations (immediate-release, SR, and XL) are bioequivalent in terms of systemic exposure to bupropion, but differ in dosing frequency 3, 4.

The maximum doses vary by formulation 2:

• Bupropion SR: 400 mg per day (200 mg twice daily)
• Bupropion XL: 450 mg per day

Special Population Adjustments

Older Adults

For older adults, start with 37.5 mg every morning, then gradually increase by 37.5 mg every 3 days as tolerated, with a maximum dose of 150 mg twice daily (300 mg total daily). 2 This lower starting dose minimizes the risk of adverse reactions in this population 2.

Hepatic Impairment

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

Renal Impairment

For patients with renal impairment (GFR <90 mL/min), reduce the total daily dose by half. 2 Bupropion and its metabolites are cleared renally and may accumulate, requiring close monitoring 2.

Critical Safety Considerations

Seizure Risk

The gradual dose titration is essential to minimize seizure risk, which is the most serious adverse effect of bupropion. 5, 6 When dosage is maintained at 450 mg/day or less in a divided schedule, the seizure rate is comparable to other antidepressants 5.

Absolute contraindications include 2, 1:

• Current or history of seizure disorders
• Current or prior diagnosis of bulimia or anorexia nervosa (increased seizure risk)
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
• Concurrent use with MAOIs (allow 14 days washout period)

Monitoring Timeline

Begin monitoring patient status, therapeutic response, and adverse effects within 1-2 weeks of initiation. 7, 2 This early monitoring is critical for detecting:

• Worsening depression or suicidal ideation (especially in patients <24 years old) 7, 2
• Agitation, irritability, or unusual behavioral changes 7
• Blood pressure elevations (bupropion can increase BP and heart rate) 2

The risk for suicide attempts is greatest during the first 1-2 months of treatment. 7, 2

Expected Response Timeline

Allow 6-8 weeks at an adequate dose before determining treatment response. 7, 2 However, patients may experience more rapid improvement in energy levels compared to other antidepressants, sometimes within the first few weeks 2. The onset of action is typically 2 weeks with full efficacy attained at 4 weeks 6.

If no adequate response occurs by 6-8 weeks at therapeutic doses, modify the treatment approach. 7, 2 Response rates to antidepressant therapy may be as low as 50% 2.

Clinical Advantages

Bupropion has a favorable side effect profile with lower rates of sexual dysfunction compared to SSRIs. 7, 2 It is particularly beneficial for patients with 7, 2:

• Depression characterized by low energy, apathy, or hypersomnia (due to activating properties)
• Concerns about sexual dysfunction or weight gain
• Comorbid nicotine dependence (FDA-approved for smoking cessation)

Important Pitfalls to Avoid

• Never crush, divide, or chew XL tablets - this destroys the extended-release mechanism and increases seizure risk 1
• Do not administer late in the day - bupropion's activating properties can cause insomnia 2
• Screen for uncontrolled hypertension - bupropion is contraindicated in this population 2
• Verify patient is not taking opioids if considering naltrexone-bupropion combination 2
• Monitor closely when switching between brand and generic formulations - historical bioequivalence issues have been reported 2