Is Wellbutrin (bupropion) effective for weight loss?

Bupropion for Weight Loss

Bupropion monotherapy produces modest weight loss (mean 2.77 kg at 6-12 months) but is not FDA-approved as a stand-alone weight loss medication; however, the combination naltrexone-bupropion ER is FDA-approved for chronic weight management in adults with obesity (BMI ≥30) or overweight with complications (BMI ≥27), making it the preferred formulation when weight loss is the primary goal. 1, 2

FDA-Approved Indications

• Bupropion alone is FDA-approved only for major depressive disorder and smoking cessation, not for weight loss 2, 3
• Naltrexone-bupropion ER (Contrave) is FDA-approved for chronic weight management as an adjunct to reduced-calorie diet and increased physical activity in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity 2

Weight Loss Efficacy

Bupropion Monotherapy

• Bupropion causes mean weight loss of 2.77 kg at 6-12 months 1
• In clinical trials for depression, 14-19% of patients lost >5 lbs on bupropion sustained-release (300-400 mg/day) compared to 6% on placebo 3
• In seasonal affective disorder trials, 23% of patients on bupropion extended-release lost >5 lbs compared to 11% on placebo over 6 months 3
• Weight loss increases with higher baseline BMI; patients with BMI ≥30 lost mean 2.4 kg after 52 weeks of treatment 4

Naltrexone-Bupropion ER Combination

• The AGA 2022 guidelines conditionally recommend naltrexone-bupropion ER for adults with obesity or overweight with weight-related complications 5
• The combination is reasonable to prioritize for patients with depressed mood, as bupropion at 300 mg daily (close to the dose in the combination) is effective for long-term treatment of recurrent major depression 5
• The combination may also benefit patients needing both weight loss and smoking cessation assistance 5

Clinical Considerations for Prescribing

When to Use Bupropion for Weight Loss

• Consider bupropion monotherapy primarily when treating depression or smoking cessation in patients who are also overweight, as it provides the dual benefit of modest weight loss 1, 3
• Prescribe naltrexone-bupropion ER when weight loss is the primary goal, particularly in patients with concurrent depression or those attempting smoking cessation 5, 1
• Bupropion consistently promotes weight loss through appetite suppression and reduced food cravings, making it the only antidepressant that actively supports weight reduction 1

Dosing and Response Assessment

• Naltrexone-bupropion ER requires weekly titration starting with 1 tablet daily (8 mg naltrexone/90 mg bupropion), escalating to maintenance dose of 2 tablets twice daily 5, 2
• Discontinue naltrexone-bupropion ER after 12 weeks if the patient has not lost 5% of total body weight, as they are likely a poor responder 5
• The second daily dose should not be taken late in the day to minimize insomnia risk 5

Dose Adjustments

• In moderate to severe renal impairment, reduce total daily dose by one-half (1 tablet twice daily) and avoid in end-stage renal disease 5, 2
• In moderate to severe hepatic impairment, do not exceed 1 tablet daily 5, 2

Critical Safety Considerations and Contraindications

Absolute Contraindications

• Avoid naltrexone-bupropion ER in patients requiring short-term or long-term opioid therapy, as naltrexone can reduce analgesic efficacy or precipitate withdrawal 5, 2
• Discontinue naltrexone-bupropion ER before procedures requiring opioid analgesia (e.g., endoscopies with fentanyl) 5, 2
• Avoid in patients with uncontrolled hypertension 5, 2
• Avoid in patients treated with or within 14 days of monoamine oxidase inhibitors 5
• Avoid in patients with current seizure disorders or any history of seizures, as bupropion lowers the seizure threshold 5, 2

Monitoring Requirements

• Monitor vital signs regularly in patients on naltrexone-bupropion ER 5
• Observe for neuropsychiatric adverse effects including suicidal thoughts and behaviors, especially in individuals younger than 24 years 5
• Counsel patients and families about the emergence of neuropsychiatric reactions 5

Cardiovascular Safety Concerns

• Long-term cardiovascular safety of naltrexone-bupropion ER remains unclear, as FDA-mandated cardiovascular outcome trials were terminated prematurely 5
• An interim analysis did not show significant increase in cardiovascular events, but definitive long-term data are lacking 5

Common Adverse Effects

• Insomnia occurs in 20% of patients on bupropion extended-release versus 13% on placebo 3
• Decreased appetite occurs in 4% versus 1% on placebo 3
• Other common effects include anxiety (7% vs 5%), nausea, dry mouth, and feeling jittery (3% vs 2%) 3
• Serious allergic reactions occur at approximately 3% rate 6

Important Clinical Pitfalls

• Do not prescribe bupropion monotherapy expecting substantial weight loss; the effect is modest (typically 2-3 kg) and should not be the sole indication 1, 7
• Bupropion alone did not improve binge eating or food craving in patients with binge-eating disorder, so it is not appropriate as stand-alone treatment for BED 8
• Remember that bupropion's weight loss effect is dose-related, with 400 mg/day producing greater weight loss (19% lost >5 lbs) than 300 mg/day (14% lost >5 lbs) 3
• Weight loss of ≥5% may improve mood in obese patients with depressive symptoms regardless of treatment, so monitor both outcomes 7