Bupropion XL Dosing Schedule
For major depressive disorder, start bupropion XL at 150 mg once daily in the morning for the first 3–4 days, then increase to the standard therapeutic dose of 300 mg once daily; the maximum dose is 450 mg once daily if needed after 6–8 weeks at 300 mg. 1, 2
Standard Dosing Protocol
Initial Titration
- Begin with 150 mg once daily in the morning for 3–4 days to assess tolerability and minimize seizure risk. 1
- Increase to 300 mg once daily (the standard therapeutic dose) starting on day 4 if the initial dose is well tolerated. 1, 2
- Administer the dose in the morning to leverage bupropion's activating properties and reduce insomnia risk. 1
Maintenance Dosing
- The standard therapeutic dose is 300 mg once daily, which provides efficacy comparable to SSRIs and other second-generation antidepressants. 1, 2
- The maximum dose is 450 mg once daily, reserved for patients who show inadequate response after 6–8 weeks at 300 mg. 1, 2
- Do not exceed 450 mg per day because seizure risk increases markedly above this threshold (from approximately 0.1% to 0.4%). 1
Timeline for Response Assessment
- Monitor patient status within 1–2 weeks of initiation, focusing on suicidal ideation, agitation, and behavioral changes—especially in patients younger than 24 years. 1
- Assess therapeutic response at 6–8 weeks at the target dose before declaring treatment failure or modifying the regimen. 1, 2
- Energy levels may improve within the first few weeks, but full antidepressant effects typically require the full 6–8-week trial. 1
Special Populations
Older Adults (≥65 Years)
- Start at 37.5 mg once daily in the morning, then increase by 37.5 mg every 3 days as tolerated. 1
- Target dose is 150 mg once daily, with a maximum of 300 mg once daily if needed. 1
- Lower starting doses reduce the risk of adverse reactions in this population. 1
Renal Impairment
- Moderate to severe renal impairment (eGFR <90 mL/min): Reduce the total daily dose by 50% (e.g., 150 mg once daily instead of 300 mg). 1
- End-stage renal disease: Avoid bupropion entirely because metabolites accumulate and dialysis does not effectively clear them. 1
Hepatic Impairment
- Moderate to severe hepatic impairment: Maximum dose is 150 mg once daily (or 150 mg every other day in severe cases). 1
- Mild hepatic impairment: Consider dose reduction and/or frequency adjustment. 1
Critical Safety Screening Before Initiation
Absolute Contraindications
- Seizure disorders or any condition predisposing to seizures (e.g., head trauma, brain tumor, stroke, eating disorders). 1, 2
- Current or recent MAOI use (within 14 days of discontinuation). 1
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs (increases seizure risk). 1
- Uncontrolled hypertension (bupropion can elevate blood pressure and heart rate). 1
Monitoring Parameters
- Blood pressure and heart rate should be measured at baseline and periodically during the first 12 weeks, as bupropion can cause modest elevations. 1
- Suicidal ideation and behavioral changes require close monitoring, especially in the first 1–2 months when suicide risk is highest. 1, 2
Formulation-Specific Considerations
- Bupropion XL is administered once daily, typically in the morning, and reaches peak plasma concentrations at approximately 5 hours. 3
- The XL formulation is bioequivalent to the immediate-release (IR) and sustained-release (SR) formulations in terms of systemic exposure to bupropion and its metabolites. 2, 3
- Switching between brand and generic formulations requires close monitoring, as historical bioequivalence issues have been reported with some generic SR products. 1
Common Pitfalls to Avoid
- Do not discontinue treatment prematurely before 6–8 weeks unless significant adverse effects occur, as response rates may be delayed. 1
- Do not exceed 450 mg per day to maintain seizure risk at approximately 0.1%. 1, 2
- Do not skip the intensive monitoring window in weeks 1–2, as this period carries the highest risk for emergent suicidal ideation. 1
- Do not combine with MAOIs or initiate within 14 days of MAOI discontinuation due to the risk of hypertensive crisis. 1
Clinical Advantages of Bupropion XL
- Lower rates of sexual dysfunction compared to SSRIs (significantly reduced risk versus escitalopram and paroxetine). 1
- Minimal weight gain or modest weight loss, unlike many other antidepressants. 1
- Lower rates of sedation compared to SSRIs, making it suitable for patients with low energy or hypersomnia. 1
- Dual benefit for patients with depression and nicotine dependence, as bupropion is also FDA-approved for smoking cessation. 1, 2