Starting Wellbutrin SR: Dosing and Titration
Start Wellbutrin SR at 150 mg once daily in the morning for 3 days, then increase to 150 mg twice daily (300 mg/day total) with at least 8 hours between doses. 1
Initial Dosing Protocol
The FDA-approved titration schedule is straightforward and designed to minimize seizure risk:
- Days 1-3: 150 mg once daily in the morning
- Day 4 onward: 150 mg twice daily (total 300 mg/day)
- Maintenance target: 300 mg/day is the usual adult target dose
This gradual dose escalation is critical for safety, particularly to reduce seizure risk 1.
Key Administration Details
Swallow tablets whole—do not crush, divide, or chew the sustained-release formulation. The medication may be taken with or without food. Ensure at least 8 hours between the morning and afternoon/evening doses 1.
Dose Escalation for Non-Responders
If no clinical improvement occurs after several weeks at 300 mg/day, you may increase to a maximum of 400 mg/day (200 mg twice daily). However, never exceed 200 mg in any single dose to avoid high peak concentrations that increase seizure risk 1.
For smoking cessation specifically, guidelines recommend initiating 1-2 weeks prior to the quit date: 150 mg once daily for days 1-3, then 150 mg twice daily from day 4 through 7-12 weeks, with a maximum of 300 mg/day 2. The ACC/AHA cardiovascular prevention guidelines similarly recommend 150 mg once daily for 3 days, then 150 mg twice daily, and note it may be combined with nicotine replacement therapy 3.
Critical Contraindications and Precautions
Absolute contraindications include:
- Seizure disorder (current or prior)
- Anorexia nervosa or bulimia (current or prior diagnosis)
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
- Concurrent MAOI use (requires 14-day washout period) 1
Bupropion lowers the seizure threshold—the incidence is approximately 0.1% (1/1,000) at 300 mg/day and increases to 0.4% (4/1,000) at the maximum 400 mg/day dose 1. Additional seizure risk factors include severe head injury, CNS tumors, stroke, metabolic disorders, illicit drug use (especially cocaine), diabetes treated with insulin or oral agents, and concomitant medications that lower seizure threshold 1.
Special Population Adjustments
Hepatic impairment:
- Moderate to severe (Child-Pugh 7-15): Maximum 100 mg/day or 150 mg every other day
- Mild (Child-Pugh 5-6): Consider dose/frequency reduction 1
Renal impairment (GFR <90 mL/min): Consider reducing dose and/or frequency 1
Monitoring Requirements
Monitor blood pressure before starting and periodically during treatment, as bupropion can cause hypertension 1. When combined with nicotine replacement therapy, hypertension risk increases (6.1% vs 2.5% with bupropion alone in one trial) 1.
Watch for neuropsychiatric adverse events including agitation, depressed mood, behavioral changes, suicidal ideation, or suicidal behavior. Instruct patients to stop the medication immediately and contact you if these occur 1. While the FDA removed the black box warning about neuropsychiatric events, monitoring remains important 3.
Common Pitfalls to Avoid
- Don't skip the 3-day titration period—jumping directly to 300 mg/day increases seizure risk
- Don't give the second dose late in the day—this increases insomnia risk 4
- Don't combine with MAOIs—requires 14-day washout in either direction 1
- Don't use in patients requiring opioid therapy—if combined with naltrexone, it will precipitate withdrawal or reduce analgesic efficacy 4
Duration of Treatment
For depression, continue treatment for several months or longer beyond acute response. Periodically reassess the need for maintenance treatment 1. For smoking cessation, the standard duration is 7-12 weeks, though therapy may be extended to 6-12 months to promote continued cessation 2.