What is the recommended dose of Bupropion (Wellbutrin) XL (Bupropion Hydrochloride Extended-Release)

Bupropion XL Dosing

For major depressive disorder, start Bupropion XL at 150 mg once daily in the morning for 1 week, then increase to the standard maintenance dose of 300 mg once daily, with a maximum dose of 450 mg daily if clinically necessary. 1, 2

Standard Dosing Regimen

• Initial dose: 150 mg once daily in the morning for the first week 1, 2
• Maintenance dose: 300 mg once daily, taken in the morning 1, 2
• Maximum dose: 450 mg once daily (do not exceed to minimize seizure risk, which remains at approximately 0.1% at this dose) 1, 2

The FDA label establishes that the 300 mg dose is effective for major depressive disorder, while the 450 mg dose demonstrated superior efficacy in one controlled trial but should be reserved for patients requiring higher doses due to increased seizure risk. 2

Special Population Adjustments

Older adults (≥55 years): Start with 37.5 mg once daily in the morning, increase by 37.5 mg every 3 days as tolerated, with a maximum of 150 mg twice daily (300 mg total daily dose). 1, 3 This lower starting dose minimizes adverse reactions in this population. 1

Hepatic impairment (moderate to severe): Do not exceed 150 mg daily (one tablet total). 1 Bupropion metabolism is significantly impaired in hepatic dysfunction, requiring dose reduction. 1

Renal impairment (GFR <90 mL/min): Reduce the total daily dose by half, as bupropion and its active metabolites accumulate with renal dysfunction. 1, 3 Close monitoring for adverse reactions is essential. 1

Timing Considerations

• Administer XL formulation once daily in the morning only to leverage its activating properties and minimize insomnia risk. 1, 3
• The extended-release formulation provides steady drug levels throughout the 24-hour period, justifying once-daily dosing. 4
• If insomnia occurs, confirm the patient is taking the medication in the morning, not later in the day. 3

Clinical Monitoring Timeline

• Week 1-2: Monitor for early adverse effects (insomnia, dry mouth, agitation) and assess for worsening depression or suicidal ideation, particularly in patients under 24 years old. 1, 2
• Week 6-8: Assess for adequate therapeutic response using standardized depression scales. 1 If no response occurs by 6-8 weeks at therapeutic doses, modify the treatment approach. 1
• Ongoing: Monitor blood pressure periodically, especially during the first 12 weeks, as bupropion can cause elevations. 3

Absolute Contraindications

• Seizure disorders or any condition lowering seizure threshold (seizure risk is approximately 0.1% at recommended doses). 1, 2, 5
• Eating disorders (bulimia or anorexia nervosa) due to significantly increased seizure risk. 1, 3
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. 1
• Current or recent MAOI use (within 14 days). 1
• Uncontrolled hypertension requires close monitoring or avoidance. 3

Critical Safety Considerations

• Black box warning: Increased risk of suicidal thoughts and behavior in patients younger than 24 years with depression, requiring close monitoring especially during the first few months of treatment. 1, 2
• Maximum daily dose must not exceed 450 mg to maintain seizure risk at 0.1%. 1, 2
• Screen all patients for seizure risk factors before initiating therapy. 5
• Avoid in patients taking tamoxifen, as bupropion may reduce tamoxifen efficacy through CYP2D6 inhibition. 1, 3

Formulation Considerations

• Bupropion XL, SR, and IR formulations are bioequivalent under steady-state conditions in terms of systemic exposure to bupropion and its metabolites. 2, 6
• Monitor closely when switching between brand and generic formulations or between SR and XL formulations, as historical bioequivalence issues have led to loss of antidepressant effect in some cases. 1
• The active metabolite hydroxybupropion achieves levels 16.4 times higher than bupropion itself and likely has key pharmacodynamic effects. 4

Common Adverse Effects Management

• Insomnia (most common): Ensure morning-only dosing of XL formulation. 3, 5
• Dry mouth: Generally transient and resolves without intervention; can reduce dose if persistent. 5
• Headache, nausea, anxiety: Usually transient and resolve within the first few weeks. 5
• These side effects occur significantly more frequently than placebo only for insomnia and dry mouth. 5