What is the recommended titration schedule for Wellbutrin (bupropion)?

Wellbutrin (Bupropion) Titration Schedule

Standard Titration for Major Depressive Disorder

For bupropion SR (sustained-release), start with 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily dose) if tolerated. 1

• The initial 3-day period at 150 mg once daily allows assessment of tolerability before advancing to the therapeutic dose 1
• Maximum dose for SR formulation is 400 mg per day, though 300 mg daily is the standard therapeutic target for most patients 1
• For bupropion XL (extended-release), start with 150 mg once daily, then increase to 300 mg once daily as the maintenance dose 1
• Maximum dose for XL formulation is 450 mg per day 1, 2

Critical Timing Considerations

Administer the first dose in the morning and any second dose (for SR formulation) before 3 PM to minimize insomnia risk. 1

• Bupropion has activating properties that can disrupt sleep if taken late in the day 1
• The twice-daily SR dosing schedule should maintain at least 8 hours between doses 1

Special Population Titration

For older adults, use a more conservative approach: start with 37.5 mg every morning, then gradually increase by 37.5 mg every 3 days as tolerated, targeting a maximum of 150 mg twice daily (300 mg total). 1

• This slower titration minimizes adverse reactions in elderly patients who have increased sensitivity 1
• The second dose must still be administered before 3 PM to prevent sleep disturbances 1

Smoking Cessation Titration

Begin with 150 mg once daily for days 1-3, then increase to 150 mg twice daily (300 mg total) if tolerated, starting 1-2 weeks before the target quit date. 1

• The 1-2 week lead time is essential to establish therapeutic drug levels before attempting cessation 1
• Maximum dose for smoking cessation is 300 mg per day (lower than for depression) to maintain seizure risk at 0.1% 1
• Continue treatment for 7-12 weeks after the quit date, with formal efficacy assessment after this period 1

Dose Adjustments for Hepatic Impairment

For moderate to severe hepatic impairment, do not exceed 150 mg daily total dose. 3, 1

• In severe hepatic impairment, consider 150 mg every other day 1
• For mild hepatic impairment, reduce dose and/or frequency 1

Dose Adjustments for Renal Impairment

For moderate to severe renal impairment (GFR <90 mL/min), reduce the total daily dose by 50%. 1

• Bupropion and its metabolites are cleared renally and may accumulate 1
• Avoid in end-stage renal disease 1

Monitoring During Titration

Monitor blood pressure and heart rate periodically, especially during the first 12 weeks, as bupropion can elevate both parameters. 1

• Assess for suicidal ideation within 1-2 weeks of initiation, particularly in patients under 24 years old 1
• The risk for suicide attempts is greatest during the first 1-2 months of treatment 1
• Allow 6-8 weeks at an adequate dose before determining treatment response 1

Critical Safety Considerations During Titration

Never exceed 450 mg per day total dose to minimize seizure risk, which is approximately 0.1% at recommended doses. 1, 4

• Screen for seizure risk factors before initiating: history of seizures, eating disorders (bulimia/anorexia), abrupt discontinuation of alcohol/benzodiazepines/antiepileptics, brain tumor, head trauma, or stroke 1, 4
• Avoid use within 14 days of MAOI discontinuation 3, 1
• Contraindicated in patients with uncontrolled hypertension 1

Common Pitfalls to Avoid

• Do not titrate too rapidly in older adults or patients on multiple medications - use the conservative 37.5 mg increments every 3 days 1
• Do not start smoking cessation treatment without the 1-2 week lead time - therapeutic levels must be established before the quit attempt 1
• Do not administer the second daily dose after 3 PM - this significantly increases insomnia risk 1
• Do not exceed 300 mg daily for smoking cessation - higher doses increase seizure risk without improving efficacy 1