What is the recommended starting dose of Wellbutrin (bupropion) for an adult patient with major depressive disorder?

Starting Dose of Wellbutrin for Major Depressive Disorder

For adult patients with major depressive disorder, 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. 1

Standard Dosing Protocol

Wellbutrin XL (Extended-Release) - Preferred Formulation

• Initial dose: 150 mg once daily in the morning 1
• Titration: After 4 days, increase to 300 mg once daily in the morning 1
• Administration: Take in the morning, with or without food; swallow whole (do not crush, divide, or chew) 1

Wellbutrin SR (Sustained-Release) - Alternative Formulation

• Initial dose: 150 mg once daily for 3 days 2
• Titration: Increase to 150 mg twice daily (300 mg total daily dose) 2
• Timing: First dose in the morning, second dose before 3 PM to minimize insomnia risk 2

Special Population Adjustments

Older Adults

• Initial dose: 37.5 mg once daily in the morning 2
• Titration: Increase by 37.5 mg every 3 days as tolerated 2
• Maximum dose: 150 mg twice daily (300 mg total daily) 2
• Rationale: Lower starting doses reduce the risk of adverse reactions in this population 2

Hepatic Impairment

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

Renal Impairment

• GFR <90 mL/min: Reduce dose and/or frequency by approximately 50% 2, 3

Critical Safety Considerations

Absolute Contraindications

• Seizure disorders: Bupropion lowers the seizure threshold 2, 3
• Current or prior bulimia or anorexia nervosa: Increased seizure risk 3
• Concurrent MAOI use or within 14 days of discontinuation: Risk of hypertensive reactions 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs: Increased seizure risk 2

Monitoring Requirements

• Suicidal ideation: Close monitoring required, especially in patients <24 years old, particularly during the first 1-2 months when suicide risk is highest 2
• Blood pressure: Monitor periodically, especially in first 12 weeks, as bupropion can elevate blood pressure and heart rate 2
• Neuropsychiatric effects: Watch for agitation, insomnia, or increased energy 2, 3

Clinical Pearls

Timing of Response

• Early monitoring: Begin assessing therapeutic response and adverse effects within 1-2 weeks 2
• Full assessment: Allow 6-8 weeks at therapeutic dose before determining treatment response 2
• Energy improvement: May occur within first few weeks, often before mood improvement 2

Ideal Patient Characteristics

• Depression with low energy, apathy, or hypersomnia (activating properties) 2
• Concerns about sexual dysfunction (lower rates than SSRIs) 2
• Concerns about weight gain (favorable profile) 2
• Comorbid smoking cessation needs 2

Common Pitfalls to Avoid

• Do not exceed 450 mg/day: Maximum dose to minimize seizure risk 2
• Do not crush or split tablets: This alters the extended-release mechanism and increases seizure risk 1
• Do not dose late in the day: Administer second dose of SR formulation before 3 PM to prevent insomnia 2
• Do not switch formulations without monitoring: Historical bioequivalence issues between brand and generic formulations require close monitoring when switching 2