What is the appropriate dose of Wellbutrin (bupropion) for an adult?

Appropriate Dose of Wellbutrin for Adults

For major depressive disorder, start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily) as the standard therapeutic dose, with a maximum of 400 mg/day for SR formulation or 450 mg/day for XL formulation. 1, 2

Standard Dosing by Formulation

Bupropion SR (Sustained Release)

• Initial dose: 150 mg once daily in the morning for the first 3 days 1
• Standard therapeutic dose: 150 mg twice daily (300 mg total daily) 1, 2
• Maximum dose: 400 mg per day 1
• Timing: First dose in the morning, second dose before 3 PM to minimize insomnia risk 1, 3

Bupropion XL (Extended Release)

• Initial dose: 150 mg once daily in the morning for 1 week 1, 2
• Standard therapeutic dose: 300 mg once daily 1
• Maximum dose: 450 mg per day 1, 2
• Timing: Take in the morning only 3

Indication-Specific Dosing

Major Depressive Disorder

• FDA-approved trials demonstrated efficacy at 300-450 mg/day, with 78% of patients treated at 300-450 mg/day 2
• The 450 mg dose showed superior efficacy in fixed-dose trials compared to 300 mg 2
• Allow 6-8 weeks at therapeutic dose before determining treatment response 1

Smoking Cessation

• Dose: 150 mg twice daily (300 mg total) of SR formulation 1
• Timing: Begin 1-2 weeks before target quit date 1
• Duration: 7-12 weeks of treatment 1

Special Population Adjustments

Older Adults (≥55 years)

• Initial dose: 37.5 mg once daily in the morning 1, 3
• Titration: Increase by 37.5 mg every 3 days as tolerated 1, 3
• Maximum dose: 150 mg twice daily (300 mg total daily) 1, 3
• This conservative approach minimizes adverse reactions in older adults who have increased risk 1

Hepatic Impairment (Moderate to Severe)

• Maximum dose: 150 mg daily (one tablet total) 1
• Bupropion is extensively metabolized hepatically, requiring significant dose reduction 1

Renal Impairment (GFR <90 mL/min)

• Dose adjustment: Reduce total daily dose by half 1, 3
• Bupropion and metabolites accumulate with renal dysfunction, requiring close monitoring 1, 3

Critical Safety Considerations

Absolute Contraindications

• Seizure disorders or conditions predisposing to seizures - bupropion lowers seizure threshold 1, 2
• Bulimia or anorexia nervosa - increased seizure risk 1, 3
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs - dramatically increases seizure risk 1
• Current MAOI use or within 14 days of discontinuing MAOIs 1
• Uncontrolled hypertension - bupropion can elevate blood pressure 1, 3

Seizure Risk Minimization

• Never exceed 450 mg/day total to keep seizure risk at approximately 0.1% 1, 2, 4
• For SR formulation, maximum single dose is 200 mg 4
• Gradual titration is essential to minimize seizure risk 1

Black Box Warning

• Increased suicidal thoughts and behavior in patients <24 years old, especially during first few months of treatment 1
• Close monitoring required, particularly in weeks 1-2 when suicide risk is greatest 1

Monitoring Parameters

Initial Assessment

• Screen for seizure risk factors, eating disorders, and uncontrolled hypertension 1, 3
• Baseline blood pressure and heart rate 3
• Mental status examination focusing on suicidal ideation 3

Ongoing Monitoring

• Blood pressure and heart rate periodically, especially first 12 weeks 3
• Neuropsychiatric symptoms: agitation, anxiety, mood changes 1, 3
• Early monitoring at 1-2 weeks for worsening depression or suicidal ideation 1
• Formal efficacy assessment at 6-8 weeks 1

Common Side Effects and Management

Most Frequent Adverse Effects

• Insomnia (most common) - managed by ensuring second SR dose is before 3 PM or taking XL in morning only 3, 4
• Dry mouth - generally transient and self-limited 4
• Headache, nausea, agitation - typically resolve within 4-5 days 5, 4

Tolerability Profile

• Discontinuation rate due to adverse events is low (6-12%) in clinical trials 4
• Lower rates of sexual dysfunction compared to SSRIs 1
• Minimal weight gain compared to other antidepressants 1
• Activating properties beneficial for patients with low energy, apathy, or hypersomnia 1

Clinical Pearls

• Bioequivalence concerns: Monitor closely when switching between brand and generic formulations or between SR and XL, as historical bioequivalence issues have been reported 1
• Combination therapy: Bupropion combined with SSRIs addresses depression through complementary mechanisms (noradrenergic/dopaminergic vs. serotonergic pathways) without significant pharmacokinetic concerns 1
• Onset of action: Energy levels may improve within first few weeks, but full antidepressant effect requires 4-6 weeks 1, 5
• Drug interactions: Exercise caution with CYP2D6 inhibitors and avoid concurrent tamoxifen use (may reduce tamoxifen efficacy) 3