How should I initiate and titrate bupropion dosing in an adult patient, including considerations for major depressive disorder, smoking cessation, age over 60, seizure risk, and hepatic impairment?

Bupropion Dosing Initiation

Start bupropion SR at 150 mg once daily in the morning for 3 days, then increase to 150 mg twice daily (300 mg total), with the second dose taken before 3 PM to minimize insomnia risk. 1

Standard Dosing Protocol for Major Depressive Disorder

• Initial dose: 150 mg once daily for the first 3 days 1
• Maintenance dose: 150 mg twice daily (300 mg total) starting on day 4 1
• Maximum dose: 400 mg/day for SR formulation or 450 mg/day for XL formulation 1
• Timing: First dose in the morning, second dose before 3 PM to prevent insomnia 1

The gradual titration from 150 mg once daily to twice daily is necessary to minimize seizure risk while achieving therapeutic levels. 1

Alternative Dosing for Older Adults (Age >60)

For patients over 60 years old, start with 37.5 mg once daily in the morning, then increase by 37.5 mg every 3 days as tolerated. 1

• Initial dose: 37.5 mg once daily in the morning 1
• Titration: Increase by 37.5 mg every 3 days 1
• Target dose: 150 mg twice daily (maximum 300 mg/day) 1
• Second dose timing: Before 3 PM to prevent sleep disturbances 1

This lower starting dose is appropriate for older adults due to increased risk of adverse reactions. 1 Elderly patients are more likely to have decreased renal function, which may lead to accumulation of bupropion and its metabolites. 2

Dosing for Smoking Cessation

Begin bupropion 1-2 weeks before the target quit date at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total). 1

• Start timing: 1-2 weeks before quit date to establish therapeutic drug levels 1
• Initial dose: 150 mg once daily for days 1-3 1
• Maintenance dose: 150 mg twice daily (300 mg total) 1
• Maximum dose: 300 mg/day for smoking cessation (do not exceed to maintain 0.1% seizure risk) 1
• Treatment duration: Continue for 7-12 weeks after quit date 1

The 1-2 week lead time before the quit date is critical and should not be skipped, as it allows therapeutic drug levels to build up before cessation attempts. 1

Critical Dose Adjustments for Special Populations

Hepatic Impairment

• Moderate to severe hepatic impairment (Child-Pugh 7-15): Maximum dose 150 mg every other day 1, 2
• Mild hepatic impairment (Child-Pugh 5-6): Reduce dose and/or frequency 1, 2

Renal Impairment

• Moderate to severe renal impairment (GFR <90 mL/min): Reduce total daily dose by 50% 1, 2
• End-stage renal disease: Avoid bupropion 1

Bupropion and its metabolites are cleared renally and may accumulate in patients with renal impairment to a greater extent than usual. 2 Monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures. 2

Absolute Contraindications (Do Not Prescribe)

Screen for these contraindications before initiating bupropion:

• Seizure disorders or any condition predisposing to seizures (brain tumor, head trauma, stroke) 1
• Current or recent MAOI use (within 14 days of discontinuing MAOIs) 1
• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs (precipitates seizures) 1
• Uncontrolled hypertension (bupropion elevates blood pressure and heart rate) 1

For naltrexone-bupropion combination products specifically, chronic opioid therapy is an absolute contraindication as naltrexone will precipitate severe withdrawal. 1

Monitoring Requirements

Initial Monitoring (First 1-2 Weeks)

• Neuropsychiatric symptoms: Monitor for agitation, restlessness, behavioral changes, and suicidal ideation, especially in patients <24 years old 1
• Blood pressure and heart rate: Check periodically, especially in first 12 weeks 1
• Seizure risk factors: Assess for any new conditions that lower seizure threshold 1

The risk for suicide attempts is greatest during the first 1-2 months of treatment. 1

Efficacy Assessment Timeline

• Early monitoring: Begin within 1-2 weeks of initiation 1
• Full response assessment: Allow 6-8 weeks at adequate dose before determining treatment response 1
• Energy improvement: May occur within first few weeks, faster than mood improvement 1

If no adequate response occurs by 6-8 weeks at therapeutic doses, modify the treatment approach by either increasing the dose (up to maximum) or adding augmentation therapy. 1

Common Pitfalls to Avoid

• Do not exceed maximum doses: 400 mg/day for SR or 450 mg/day for XL to maintain seizure risk at 0.1% 1
• Do not give second dose after 3 PM: This causes insomnia due to bupropion's activating properties 1
• Do not skip the 1-2 week lead time for smoking cessation: Therapeutic levels must be established before quit attempts 1
• Do not start at full dose in elderly patients: Use 37.5 mg starting dose and titrate slowly 1
• Do not combine with MAOIs or use within 14 days of MAOI discontinuation 1
• Do not switch between brand and generic formulations without close monitoring: Historical bioequivalence issues may lead to loss of antidepressant effect 1

Clinical Advantages of Bupropion

• Lower sexual dysfunction rates compared to SSRIs 1
• Minimal weight gain or weight loss unlike many other antidepressants 1
• Beneficial for patients with low energy, apathy, or hypersomnia due to activating properties 1
• Addresses both depression and smoking cessation simultaneously in patients with both conditions 1