How Soon to Increase Bupropion XL
For bupropion XL, increase the dose from 150 mg to 300 mg once daily after 4 days of initial dosing. 1
Standard Titration Protocol
The FDA-approved dosing schedule for bupropion XL is straightforward and evidence-based:
- Start with 150 mg once daily in the morning 1
- After exactly 4 days, increase to the target dose of 300 mg once daily if the medication is tolerated 1
- This rapid titration is safe because the extended-release formulation delivers medication gradually throughout the day, with peak plasma concentrations occurring around 5 hours post-dose 2
Why 4 Days Is the Correct Interval
The 4-day waiting period is based on pharmacokinetic principles:
- Bupropion has a half-life of approximately 21 hours, and its primary active metabolite hydroxybupropion has a half-life of approximately 20 hours 2
- Steady-state plasma concentrations are achieved within 5–7 days of consistent dosing 2
- The 4-day interval allows sufficient time to assess initial tolerability (insomnia, anxiety, tremor) before reaching the therapeutic dose 1
- At steady state, hydroxybupropion concentrations are 4- to 7-fold higher than the parent drug, making gradual dose escalation critical to minimize seizure risk 2
Maximum Dose and Safety Limits
- The maximum dose for bupropion XL is 450 mg per day 3
- For major depressive disorder, the standard therapeutic dose is 300 mg/day; doses above this should only be considered after 6–8 weeks if response is inadequate 3, 1
- Never exceed 450 mg/day because seizure risk increases markedly above this threshold 3
Special Populations Requiring Slower Titration
Older Adults
- Start with 37.5 mg every morning, then increase by 37.5 mg every 3 days as tolerated, with a maximum of 150 mg twice daily (300 mg total) 3
- This slower schedule (every 3 days instead of 4 days) reduces the risk of adverse reactions in elderly patients 3
Hepatic Impairment
- Moderate to severe impairment (Child-Pugh 7–15): maximum dose is 150 mg every other day 1
- Mild impairment (Child-Pugh 5–6): reduce dose and/or frequency 1
Renal Impairment
- GFR <90 mL/min: reduce total daily dose by 50% (e.g., 150 mg instead of 300 mg) 3, 1
- End-stage renal disease: avoid bupropion entirely because metabolites accumulate and dialysis does not clear hydroxybupropion 3
Critical Safety Screening Before Any Dose Increase
Before increasing from 150 mg to 300 mg, confirm the patient does not have:
- Seizure history or any condition predisposing to seizures (head trauma, brain tumor, stroke, eating disorders) 1
- Current or recent MAOI use (within 14 days) 1
- Uncontrolled hypertension (bupropion can elevate blood pressure) 3
- Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs (increases seizure risk) 3
Monitoring During Dose Escalation
- Assess for neuropsychiatric symptoms within 1–2 weeks of starting or increasing the dose, especially in patients younger than 24 years (highest risk for suicidal ideation) 3
- Monitor blood pressure and heart rate, particularly in the first 12 weeks 3
- Watch for insomnia: administer bupropion XL in the morning to minimize sleep disturbance 3
When to Wait Longer Than 4 Days
Do not increase the dose on day 5 if the patient experiences:
- Significant anxiety, agitation, or tremor 3
- Insomnia severe enough to impair function 3
- Any new-onset neurologic symptoms (e.g., myoclonus, confusion) that could signal metabolite accumulation 2
In these cases, maintain 150 mg for an additional 1–2 weeks to allow tolerance to develop before attempting dose escalation 3.