When should Wellbutrin (bupropion) be prescribed to patients?

When to Prescribe Wellbutrin (Bupropion)

Wellbutrin should be prescribed as a first-line antidepressant for major depressive disorder, with particular priority for patients who have low energy, apathy, concerns about sexual dysfunction, or who need concurrent smoking cessation. 1, 2

Primary Indications

Major Depressive Disorder

• Bupropion is FDA-approved and equally effective as other second-generation antidepressants for treating acute major depression, with the American College of Physicians recommending selection based on side effect profile rather than efficacy differences. 1
• Prioritize bupropion for patients with depression characterized by low energy, apathy, or hypersomnia due to its activating dopaminergic and noradrenergic properties. 2
• Bupropion demonstrates significantly lower rates of sexual dysfunction compared to SSRIs like fluoxetine, sertraline, and especially paroxetine, making it the preferred choice for patients concerned about sexual side effects. 1

Seasonal Affective Disorder (SAD)

• Bupropion XL 300 mg daily is FDA-approved for preventing seasonal major depressive episodes, with treatment initiated in autumn before symptom onset and continued through winter. 3
• Clinical trials demonstrate a 44% relative risk reduction in depression recurrence when bupropion is started preventively while patients are still well. 4

Smoking Cessation

• Bupropion SR 150 mg twice daily (300 mg total) is FDA-approved for smoking cessation, with treatment beginning 1-2 weeks before the target quit date and continuing for 7-12 weeks. 2, 5
• Consider bupropion particularly for patients who need both depression treatment and smoking cessation, as it addresses both conditions simultaneously. 1, 2

Weight Management (Naltrexone-Bupropion Combination)

• The naltrexone-bupropion ER combination should be prioritized for appropriate patients with obesity who also have depressed mood or need smoking cessation assistance. 1

Absolute Contraindications (Do Not Prescribe)

• Seizure disorder or history of epilepsy - bupropion significantly lowers seizure threshold with dose-dependent risk (0.1% at ≤300 mg/day). 6, 3
• Current or prior bulimia or anorexia nervosa - higher seizure incidence observed in these populations. 6, 3
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs - dramatically increases seizure risk. 2, 3
• Concurrent MAOI use or within 14 days of MAOI discontinuation - risk of hypertensive crisis. 6, 3
• Uncontrolled hypertension - bupropion can elevate blood pressure. 1, 6

Critical Pre-Treatment Screening

Required Assessments Before Prescribing

• Screen for seizure risk factors: personal or family history of seizures, head trauma, brain metastases, CNS tumors, or conditions lowering seizure threshold. 6
• Verify no current eating disorder diagnosis (bulimia or anorexia nervosa). 6
• Confirm patient is not taking opioids if considering naltrexone-bupropion combination. 2
• Measure baseline blood pressure and heart rate - monitor periodically during treatment, especially first 12 weeks. 2
• Assess for suicidal ideation, particularly in patients under 24 years who require close monitoring for increased suicidal thoughts. 2, 3

Medication Reconciliation

• Confirm no concurrent MAOI therapy or use within past 14 days. 3
• Review all medications metabolized by CYP2D6, as bupropion inhibits this enzyme. 7
• Ensure patient is not taking other bupropion-containing products (ZYBAN, other Wellbutrin formulations). 3

Dosing Strategy

Standard Initiation for Depression

• Start bupropion SR 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total). 2
• For bupropion XL, start 150 mg once daily in the morning, may increase to 300 mg once daily after 7 days. 3
• Maximum dose: 400 mg/day for SR formulation, 450 mg/day for XL formulation. 2

Special Population Adjustments

• Older adults: Start 37.5 mg every morning, increase by 37.5 mg every 3 days as tolerated, maximum 150 mg twice daily (300 mg total). 2
• Moderate to severe hepatic impairment (Child-Pugh 7-15): Maximum 150 mg every other day. 3
• Renal impairment (GFR <90 mL/min): Reduce total daily dose by half. 2, 3

Timing Considerations

• Administer first dose in the morning to leverage activating properties. 2
• Give second dose (SR formulation) before 3 PM to minimize insomnia risk. 2

Monitoring Requirements

Initial Phase (First 1-2 Weeks)

• Assess patient status within 1-2 weeks of initiation for therapeutic response and adverse effects. 1
• Monitor closely for emergence of agitation, irritability, unusual behavior changes, or suicidal thoughts - particularly in patients under 24 years. 1, 3

Ongoing Monitoring

• Allow 6-8 weeks at adequate dose before determining treatment response. 1, 2
• If no adequate response after 6-8 weeks, modify treatment approach. 1
• Monitor blood pressure and heart rate periodically, especially during first 12 weeks. 2

Clinical Advantages Over Other Antidepressants

• Lowest sexual dysfunction rate among antidepressants - significantly lower than SSRIs. 1
• No weight gain - unlike many TCAs and some SSRIs. 8
• Minimal anticholinergic effects - less dry mouth, constipation than TCAs. 9
• Less somnolence - compared to TCAs and some SSRIs. 8
• May be less likely to provoke mania than serotonergic antidepressants. 7
• Dual benefit for depression and smoking cessation when both are needed. 1, 5

Common Pitfalls to Avoid

• Never exceed 300 mg per single dose - increases seizure risk substantially. 2
• Do not crush, divide, or chew extended-release formulations - alters release rate and increases seizure risk. 3
• Avoid late-day dosing - causes insomnia due to activating properties. 2
• Do not combine with other bupropion-containing products - risk of overdose and seizures. 3
• Monitor for decreased alcohol tolerance during treatment. 3