What is the recommended dosing for a typical adult patient starting bupropion (Wellbutrin) with no history of seizures or impaired renal function?

Starting Bupropion (Wellbutrin) Dosing

For a typical adult starting bupropion for major depressive disorder, begin with 150 mg once daily in the morning, then increase to 150 mg twice daily (300 mg total) after 3-4 days if tolerated. 1, 2

Initial Dosing Strategy

For Bupropion SR (Sustained Release):

• Start with 150 mg once daily in the morning 1
• After 3 days, increase to 150 mg twice daily (300 mg total daily dose) 1
• The second dose must be taken before 3 PM to minimize insomnia risk 1
• Maximum dose: 400 mg/day 1

For Bupropion XL (Extended Release):

• Start with 150 mg once daily in the morning 2
• After 4 days, may increase to 300 mg once daily 2
• Maximum dose: 450 mg/day 2
• Take the entire dose in the morning 1

Rationale for Gradual Titration

The gradual dose escalation is critical to minimize seizure risk, which is dose-dependent 2, 3. At doses ≤450 mg/day with proper titration, the seizure incidence is approximately 0.1% (1 in 1,000), comparable to other antidepressants 4, 5. However, seizure risk increases substantially with higher doses or rapid titration 6, 3.

Timeline for Clinical Response

• Early monitoring: Begin assessing within 1-2 weeks for adverse effects and worsening depression 1
• Energy improvement: May occur within the first few weeks due to bupropion's activating properties 1
• Full therapeutic assessment: Allow 6-8 weeks at an adequate dose before determining treatment response 1
• Critical monitoring period: Suicide risk is highest during the first 1-2 months, particularly in patients under 24 years old 1

Absolute Contraindications

Bupropion must not be used in patients with: 2

• Current or prior seizure disorder 2
• Current or prior diagnosis of bulimia or anorexia nervosa 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2
• Current MAOI use or within 14 days of MAOI discontinuation 2
• Known hypersensitivity to bupropion 2

Critical Safety Monitoring

Blood Pressure Monitoring:

• Check blood pressure before initiating treatment 1
• Monitor periodically during treatment, especially in the first 12 weeks 1
• Avoid in patients with uncontrolled hypertension 1

Mental Status Monitoring:

• Screen for suicidal ideation at baseline and throughout treatment 1
• Monitor closely for worsening depression, agitation, or behavioral changes 1
• Patients under 24 years require particularly close monitoring due to FDA black box warning for increased suicidal thoughts 1

Common Pitfalls to Avoid

Never split, crush, or divide XL formulation - this destroys the extended-release mechanism and increases seizure risk 7

Avoid late-day dosing - the second SR dose or single XL dose should be taken in the morning or early afternoon to prevent insomnia 1

Do not exceed maximum daily doses - 400 mg/day for SR, 450 mg/day for XL to maintain seizure risk at acceptable levels 1, 2

Do not discontinue abruptly in high-risk patients - while bupropion can be stopped without tapering in most cases, patients with severe depression should be monitored closely for mood destabilization 7

Advantages of Bupropion

Bupropion offers distinct benefits compared to SSRIs: 1

• Lower rates of sexual dysfunction 1
• No weight gain (may cause weight loss) 1
• Activating properties beneficial for patients with low energy, apathy, or hypersomnia 1
• Dual benefit for patients with comorbid depression and nicotine dependence 1