What is the recommended dose of Bupropion (Wellbutrin) for a patient with a history of depression and/or smoking seeking to lose weight?

Bupropion for Weight Loss: Dosing Recommendations

For weight loss, bupropion should be prescribed as the FDA-approved combination product naltrexone/bupropion extended-release (Contrave), not as bupropion monotherapy, with a target maintenance dose of 32 mg naltrexone/360 mg bupropion daily (two tablets twice daily). 1

FDA-Approved Dosing for Weight Management

The only FDA-approved formulation of bupropion for weight loss is the naltrexone/bupropion ER combination product. 1 Bupropion monotherapy (Wellbutrin) is not FDA-approved for obesity treatment, though it has shown weight loss effects in clinical trials. 1

Titration Schedule for Naltrexone/Bupropion ER

The medication must be titrated gradually over 4 weeks to minimize side effects: 2

• Week 1: 8 mg naltrexone/90 mg bupropion once daily in the morning 2
• Week 2: 8 mg naltrexone/90 mg bupropion twice daily (morning and evening) 2
• Week 3: 16 mg naltrexone/180 mg bupropion in the morning + 8 mg naltrexone/90 mg bupropion in the evening 2
• Week 4 and beyond: 16 mg naltrexone/180 mg bupropion twice daily (maintenance dose) 2

The second dose should be taken before 3 PM to minimize insomnia risk. 2

Clinical Evidence for Weight Loss

In four major trials (COR-I, COR-II, COR-BMOD, COR-Diabetes) involving 4,536 patients with overweight or obesity, naltrexone/bupropion demonstrated significant weight loss compared to placebo: 1

• At 56 weeks: 6.1% weight loss with naltrexone/bupropion versus 1.3% with placebo 1
• Clinically significant weight loss (≥5%): 48% of treatment group versus 16% of placebo group 1
• In diabetic patients: 44.5% achieved ≥5% weight loss versus 18.9% with placebo, with 0.6% reduction in hemoglobin A1c 1

Bupropion monotherapy studies showed more modest weight loss of 2.77 kg at 6-12 months. 1

Ideal Candidates for Naltrexone/Bupropion

This combination is particularly beneficial for patients with: 1

• Comorbid depression (bupropion treats both conditions simultaneously) 1
• Active smoking or desire to quit (bupropion aids smoking cessation) 1
• Food cravings or addictive eating behaviors (naltrexone blocks reward pathways) 1
• Type 2 diabetes (demonstrated A1c reduction in clinical trials) 1

The combination is neither a controlled substance nor requires injection, unlike other obesity medications. 1

Absolute Contraindications

Do not prescribe naltrexone/bupropion in patients with: 1, 2, 3

• Uncontrolled hypertension (bupropion elevates blood pressure and heart rate) 1, 2
• Seizure history or any condition predisposing to seizures (bupropion lowers seizure threshold) 1, 2
• Eating disorders (anorexia or bulimia nervosa—electrolyte disturbances synergistically increase seizure risk) 1, 3
• Current opioid use (naltrexone precipitates severe withdrawal) 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs (increases seizure risk) 2
• Current or recent MAOI use (within 14 days) 1
• Pregnancy or inadequate contraception (contraindicated in women who may become pregnant) 2
• Moderate to severe hepatic impairment (maximum dose 150 mg daily) 2
• Moderate to severe renal impairment (reduce dose by 50%) 2

Critical Safety Monitoring

Before Initiating Treatment

Screen for: 2

• Opioid medication use (absolute contraindication with naltrexone) 2
• Baseline blood pressure and heart rate (monitor for elevations) 2
• Seizure risk factors (history, head trauma, brain lesions, metabolic disorders) 2
• Eating disorder history (detailed questioning about purging, restriction, compensatory behaviors) 3
• Suicidal ideation (especially in patients under 24 years old) 2

During Treatment

Monitor regularly for: 1, 2

• Blood pressure and heart rate (especially first 12 weeks—bupropion can cause elevations) 2
• Neuropsychiatric symptoms (mood changes, suicidal thoughts, agitation) 1, 2
• Weight loss progress (assess efficacy at 12 weeks; discontinue if <5% weight loss) 1

Common Side Effects

The most frequent adverse effects include: 1

• Nausea (most common—dose titration helps minimize) 1
• Constipation 1
• Headache 1
• Dizziness 1
• Insomnia (mitigated by avoiding late-day dosing) 1
• Dry mouth 1

Black Box Warning

Bupropion carries an FDA black box warning for increased suicidal thoughts in young adults (under 24 years) within the first few months of treatment. 1 Close monitoring is mandatory during treatment initiation, though no suicidality was reported in phase 3 obesity trials. 1

Dose Adjustments for Special Populations

Hepatic Impairment

• Moderate to severe impairment: Maximum 150 mg daily (one tablet) 2
• Mild impairment: Consider dose reduction and/or decreased frequency 2

Renal Impairment

• Moderate to severe (GFR <90 mL/min): Reduce total daily dose by 50% 2
• End-stage renal disease: Avoid use 2

Older Adults

Start with lower doses (approximately 50% of standard dose) and titrate more gradually due to increased risk of adverse reactions. 2

Clinical Pearls

• Bupropion monotherapy is NOT FDA-approved for weight loss and should not be prescribed off-label for this indication when the approved combination product exists. 1
• Weight loss effects are modest (mean 6.1% at 56 weeks) and require concurrent lifestyle modification. 1
• The naltrexone component is essential for weight loss efficacy—it blocks an inhibitory feedback loop that would otherwise limit bupropion's anorectic properties. 1
• Patients with depression benefit doubly from addressing both mood and weight concerns simultaneously. 1
• Smoking cessation patients may experience less weight gain when using bupropion, making this combination particularly valuable for smokers seeking weight management. 1, 4