Bupropion XL Titration Schedule for Starting Treatment
For patients starting bupropion HCl ER (XL) 150 mg with a target dose of 300 mg once daily, begin with 150 mg once daily in the morning for 4-7 days, then increase to 300 mg once daily if tolerated. 1
Standard Titration Protocol
Initial Dosing Phase
- Start with 150 mg once daily in the morning as the initial dose 2, 1
- The FDA label specifies that after 4 days at 150 mg, the dose may be increased to 300 mg once daily for major depressive disorder 1
- For seasonal affective disorder, the FDA recommends waiting one week before increasing to 300 mg once daily 1
- All doses should be administered in the morning to minimize insomnia risk 2, 3
Target Maintenance Dose
- The usual target dose is 300 mg once daily for both major depressive disorder and seasonal affective disorder 2, 1
- The maximum recommended dose for bupropion XL is 450 mg per day, though 300 mg is the standard therapeutic target 2
Critical Safety Considerations During Titration
Seizure Risk Minimization
- Gradual dose escalation is essential to reduce seizure risk, which is dose-related 1, 4
- The seizure risk at doses ≤450 mg/day is approximately 0.1% (1 in 1,000), comparable to other antidepressants when properly dosed 2, 4
- Never split, crush, or divide the XL formulation, as this destroys the extended-release properties and increases seizure risk 3
Monitoring Requirements
- Begin monitoring for therapeutic response and adverse effects within 1-2 weeks of initiation 2
- Close monitoring for suicidal ideation is critical, particularly in patients under 24 years old, during the first 1-2 months when suicide risk is greatest 2, 1
- Monitor blood pressure before initiating treatment and periodically during treatment, as bupropion can cause elevations 2, 1
Special Population Adjustments
Older Adults
- For older adults, consider starting with 37.5 mg once daily in the morning, increasing by 37.5 mg every 3 days as tolerated, with a maximum of 150 mg twice daily (300 mg total daily) 2
- Lower starting doses minimize the risk of adverse reactions in this population 2
Hepatic Impairment
- For moderate to severe hepatic impairment, the maximum dose is 150 mg every other day 2, 1
- For mild hepatic impairment, consider reducing the dose and/or frequency of dosing 1
Renal Impairment
- For patients with renal impairment (GFR <90 mL/min), reduce the total daily dose by half and consider extending the duration at each dose level 2, 1
- Bupropion and its metabolites are cleared renally and may accumulate, requiring close monitoring 2
Timeline for Clinical Response
Expected Improvement Window
- Allow 6-8 weeks at an adequate dose before determining treatment response 2
- Energy levels may improve more rapidly, sometimes within the first few weeks, due to bupropion's activating properties 2
- If no adequate response occurs by 6-8 weeks at therapeutic doses, modify the treatment approach 2
Early Monitoring Strategy
- Assess patient status, therapeutic response, and adverse effects within 1-2 weeks of initiation 2
- Monitor for worsening depression, suicidal ideation, or behavioral changes, particularly in patients under 24 years 2, 1
Common Pitfalls to Avoid
Absolute Contraindications
- Seizure disorder is an absolute contraindication 1, 4
- Current or prior diagnosis of bulimia or anorexia nervosa due to increased seizure risk 2, 1
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs increases seizure risk 2, 1
- Do not use with MAOIs or within 14 days of stopping an MAOI 1
Relative Contraindications
- Uncontrolled hypertension should preclude bupropion use, as the medication can elevate blood pressure and heart rate 2
- Any condition that predisposes to seizures warrants extreme caution or avoidance 2
Clinical Advantages of This Formulation
- The XL formulation allows for once-daily dosing, improving adherence compared to SR (twice daily) or IR (three times daily) formulations 5, 6
- Bupropion XL has a favorable side effect profile with lower rates of sexual dysfunction compared to SSRIs 2
- The extended-release formulation provides steady drug levels throughout the day with peak concentration at approximately 5 hours 6