Initiating Wellbutrin (Bupropion) Therapy
Start with bupropion SR 150 mg once daily for 3-4 days, then increase to 150 mg twice daily (300 mg total daily dose) if tolerated. 1, 2
Standard Dosing Protocol for Major Depressive Disorder
Initial Titration Schedule
- Begin with 150 mg once daily for the first 3-4 days to minimize seizure risk 1, 2
- Increase to 150 mg twice daily (300 mg total) after the initial titration period if the patient tolerates the starting dose 1, 2
- The gradual dose escalation is critical to reduce seizure risk, which is dose-dependent 2
Target and Maximum Dosing
- Usual target dose is 300 mg daily (150 mg twice daily for SR formulation) 1, 2
- Maximum dose is 400 mg daily for SR formulation (not to exceed 450 mg for XL formulation) 1, 2
- If using the XL (extended-release) formulation instead, start with 150 mg once daily, then increase to 300 mg once daily after one week 1, 2
Special Population Considerations
Older Adults
- Start with 37.5 mg every morning, then gradually increase by 37.5 mg every 3 days as tolerated 1
- Maximum dose of 150 mg twice daily (300 mg total) for geriatric patients 1
- Administer the second dose before 3 p.m. to minimize insomnia risk 1
Hepatic Impairment
- Moderate to severe hepatic impairment: 150 mg every other day 1, 2
- Mild hepatic impairment: Consider reducing dose and/or frequency 2
Renal Impairment
- Reduce total daily dose by half for patients with moderate to severe renal impairment (GFR <90 mL/min) 1, 2
- Bupropion and its metabolites are cleared renally and may accumulate 1
Critical Safety Considerations
Absolute Contraindications
- Seizure disorders - bupropion lowers seizure threshold 1, 2
- Current or prior bulimia or anorexia nervosa - increased seizure risk 1, 2
- Concurrent MAOI use or within 14 days of discontinuing MAOIs 1, 2
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2
Monitoring Requirements
- Monitor for neuropsychiatric adverse effects, especially in patients younger than 24 years 1
- Monitor blood pressure before and periodically during treatment, as bupropion can cause hypertension 2
- Screen patients for bipolar disorder before initiating treatment to avoid precipitating mania 2
Timing of Efficacy Assessment
- Initial response may be seen within 1-2 weeks, but full therapeutic effect typically requires 4-6 weeks 3, 4
- If no response after 6-8 weeks at adequate dose, consider alternative treatment 1
Common Pitfalls to Avoid
- Never exceed 150 mg per single dose for SR formulation to minimize seizure risk 2
- Do not increase dose more frequently than every 3-4 days during initial titration 2
- Most common adverse effects (insomnia, dry mouth) are generally transient and resolve without intervention 5
- Insomnia can be minimized by avoiding late-day dosing 1