What is the recommended dosing regimen for Wellbutrin (bupropion) for the first two days of treatment?

Wellbutrin Initial Two-Day Dosing

For Wellbutrin XL (extended-release), start with 150 mg once daily in the morning for the first 4 days before increasing to the target dose of 300 mg daily. 1

Formulation-Specific Initial Dosing

Wellbutrin XL (Extended-Release)

• Days 1-4: 150 mg once daily in the morning 1
• Day 5 onward: May increase to 300 mg once daily 1
• This gradual titration minimizes seizure risk while achieving therapeutic levels 2
• Must be swallowed whole—never crushed, divided, or chewed 1
• Can be taken with or without food 1

Wellbutrin SR (Sustained-Release)

• Days 1-3: 150 mg once daily 2
• Day 4 onward: Increase to 150 mg twice daily (300 mg total) if tolerated 2
• The second dose should be administered before 3 p.m. to minimize insomnia risk 2

Critical Safety Considerations During Initial Dosing

The gradual dose escalation is mandatory to minimize seizure risk, which occurs in approximately 0.1% of patients at recommended doses. 3

Absolute Contraindications to Screen For:

• Active seizure disorder or history of seizures 2, 1
• Current MAOI use or within 14 days of MAOI discontinuation 2, 1
• Bulimia or anorexia nervosa (increased seizure risk) 2
• Patients taking tamoxifen 2

Monitoring During First Two Days:

• Blood pressure (avoid in uncontrolled hypertension) 2
• Neuropsychiatric symptoms, especially in patients under 24 years 2

Special Population Adjustments for Initial Dosing

Older Adults (≥65 years):

• Start with 37.5 mg every morning, then increase by 37.5 mg every 3 days as tolerated 2
• This represents approximately 50% of standard dosing due to increased adverse reaction risk 2

Hepatic Impairment:

• Moderate to severe (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 half 2
• Consider reducing frequency of administration 1

Common Pitfalls to Avoid

• Never exceed 300 mg/day during initial titration for depression 1—the maximum dose of 450 mg/day for XL is only considered after adequate trial at lower doses 2
• Do not split or crush XL tablets—this destroys the extended-release mechanism and increases seizure risk 1
• Avoid evening dosing—insomnia is the most common adverse effect, occurring more frequently than with placebo 3
• Do not rush titration—the 4-day waiting period for XL and 3-day period for SR are designed to minimize seizure risk 2, 1

Expected Tolerability During Initial Days

The most common adverse effects during the first two days include insomnia, dry mouth, headache, and nausea 3. These are generally transient and often resolve without intervention 3. Only insomnia and dry mouth occur significantly more frequently than placebo 3.