Bupropion (Wellbutrin) Dosing for Weight Loss
For weight loss purposes, bupropion should be started at 150 mg daily and gradually increased to 300-400 mg daily (divided into two doses) as the maximum effective dose. 1, 2, 3
Dosing Protocol
- Initial dose: 150 mg once daily for 1 week
- Titration: Increase to 150 mg twice daily (300 mg total) after 1-2 weeks
- Maximum dose: Can be further increased to 200 mg twice daily (400 mg total) if needed and tolerated
- Duration: Continue for at least 24 weeks to achieve and maintain weight loss
- Monitoring: Evaluate weight loss at 8-12 weeks; discontinue if <5% weight loss is not achieved
Evidence for Weight Loss Efficacy
Bupropion has demonstrated effectiveness for weight loss in clinical trials:
- In an 8-week randomized controlled trial, subjects taking bupropion achieved 4.9% weight loss compared to 1.3% with placebo 2
- A 48-week study showed weight loss of 7.2% with bupropion SR 300 mg/day and 10.1% with 400 mg/day, compared to 5.0% with placebo 3
- Weight loss with bupropion is dose-dependent, with higher doses (400 mg/day) producing greater weight loss than lower doses (300 mg/day) 3
Mechanism of Action for Weight Loss
Bupropion works as a dopamine/norepinephrine reuptake inhibitor that:
- Reduces appetite and food cravings
- Increases energy expenditure
- Activates POMC neurons in the hypothalamus, which helps control feeding and body weight 1
Patient Selection
Bupropion may be particularly beneficial for:
- Patients who describe food cravings or addictive behaviors related to food 1
- Patients with comorbid depression 1
- Patients attempting to quit smoking concurrently with weight loss efforts 1
Contraindications and Precautions
Bupropion should NOT be used in patients with:
- Seizure disorders or conditions that lower seizure threshold
- Current or prior diagnosis of anorexia nervosa or bulimia
- Uncontrolled hypertension (monitor blood pressure regularly)
- Recent use of MAO inhibitors (within 14 days)
- History of closed-angle glaucoma 1, 4, 5
Monitoring and Side Effects
Common side effects include:
- Insomnia (20% vs 13% placebo)
- Dry mouth
- Headache
- Anxiety (7% vs 5% placebo)
- Decreased appetite (4% vs 1% placebo)
- Nausea
- Constipation 5
Monitor for:
- Blood pressure and heart rate increases
- Neuropsychiatric symptoms (especially in patients younger than 24 years)
- Weight loss progress at 8-12 weeks
Important Considerations
- Bupropion is not FDA-approved specifically for weight loss but is used off-label for this purpose
- It is FDA-approved as part of a combination product (bupropion/naltrexone) for weight management 1
- When used alone for weight loss, bupropion produces modest but significant weight reduction
- For optimal results, combine with caloric restriction and increased physical activity
- Weight loss effects may plateau after 24-48 weeks
Practical Recommendation
For patients seeking weight loss with bupropion, use the sustained-release (SR) or extended-release (XL) formulation to improve adherence and minimize side effects. The SR formulation can be given twice daily (morning and evening), while the XL formulation can be given once daily in the morning to minimize sleep disturbances.