What is the recommended dosing for Wellbutrin (bupropion) in the treatment of depression?

Wellbutrin (Bupropion) Dosing for Depression

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 dose), or use bupropion XL 150 mg once daily initially, titrating to 300 mg once daily as the maintenance dose. 1

Standard Dosing Regimens

Bupropion SR (Sustained Release)

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

Bupropion XL (Extended Release)

• Initial dose: 150 mg once daily 1
• Maintenance dose: 150-300 mg once daily 1
• Maximum dose: 450 mg per day 1
• Timing: Administer in the morning 1

Dose Adjustments for Special Populations

Older Adults

• Start lower: 37.5 mg every morning 1
• Titration: Increase by 37.5 mg every 3 days as tolerated 1
• Maximum: 150 mg twice daily (300 mg total daily dose) 1
• Rationale: Lower starting doses minimize risk of adverse reactions in this population 1

Hepatic Impairment

• Moderate to severe hepatic impairment: Do not exceed 150 mg daily (one tablet total) 1

Renal Impairment

• Moderate to severe renal impairment (GFR <90 mL/min): Reduce total daily dose by half 1
• Monitoring: Close surveillance for adverse reactions required due to accumulation of bupropion and metabolites 1

Clinical Monitoring and Response Assessment

Early Monitoring (Weeks 1-2)

• Begin monitoring within 1-2 weeks of initiation for therapeutic response and adverse effects 2
• Critical focus: Assess for worsening depression, suicidal ideation, agitation, irritability, or unusual behavioral changes 2
• Highest risk period: Suicide attempts are most likely during the first 1-2 months of treatment 1

Response Assessment (Weeks 6-8)

• Allow 6-8 weeks at adequate dose before determining treatment response 2, 1
• If no adequate response: Modify treatment approach after this timeframe 2
• Important caveat: Response rates to antidepressant therapy may be as low as 50% 2

Absolute Contraindications

Bupropion must be avoided in the following situations:

• Seizure disorders: Bupropion lowers seizure threshold 1
• Current or recent MAOI use: Contraindicated within 14 days of discontinuing MAOIs 1
• Bulimia or anorexia nervosa: Increased seizure risk in these populations 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs: Absolute contraindication due to seizure risk 1
• Uncontrolled hypertension: Bupropion can elevate blood pressure and heart rate 1

Clinical Advantages and Patient Selection

Bupropion offers specific advantages over SSRIs:

• Lower rates of sexual dysfunction compared to fluoxetine or sertraline 2
• Less somnolence than many tricyclic antidepressants 3, 4
• Activating properties: Particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia 1
• Dual indication: May address both depression and smoking cessation simultaneously 1

Critical Safety Considerations

Maximum Dosing to Minimize Seizure Risk

• Never exceed 450 mg per day to minimize seizure risk 1
• Seizure rate: When maintained at 450 mg/day or less in divided doses, seizure rate is comparable to other antidepressants 5

Black Box Warning

• Increased suicidal thoughts and behavior in patients younger than 24 years with depression 1
• Close monitoring required: Especially during first few months of treatment 1

Drug Interactions

• CYP2D6 inhibition: Bupropion significantly increases levels of drugs metabolized by CYP2D6 (e.g., desipramine levels increased 5-fold) 6
• Tamoxifen interaction: Contraindicated in patients taking tamoxifen 1

Formulation Bioequivalence

All three formulations (IR, SR, XL) are bioequivalent in terms of systemic exposure to bupropion under steady-state conditions 6, 3, 4

Important Caveat on Generic Formulations

• Monitor closely when switching between brand and generic formulations or between SR and XL formulations 1
• Historical bioequivalence issues: Some generic versions of bupropion SR were previously found not bioequivalent to brand-name Wellbutrin SR, potentially leading to loss of antidepressant effect 1

Treatment Modification Algorithm

If inadequate response after 6-8 weeks at therapeutic dose:

1. Consider augmentation strategies (e.g., adding bupropion to SSRIs shows better outcomes than buspirone augmentation) 1
2. Switch to alternative antidepressant 2
3. Evaluate for combination therapy 2

Do not discontinue prematurely before 6-8 weeks unless significant adverse effects occur 1