What is the recommended dosing for bupropion (Wellbutrin) SR in a patient with potential seizure history, eating disorders, or impaired renal or hepatic function?

Bupropion SR Dosing

Standard Dosing for Major Depressive Disorder

For bupropion SR in major depressive disorder, start with 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily dose), with a maximum dose of 400 mg/day. 1

• The initial 3-day period at 150 mg once daily allows assessment of tolerability before dose escalation 1
• The target therapeutic dose is 300 mg/day (150 mg twice daily), which provides optimal efficacy for most patients 2
• If inadequate response after 6-8 weeks at 300 mg/day, the dose may be increased to a maximum of 400 mg/day for the SR formulation 1

Critical Timing Considerations

Administer the first dose in the morning and the second dose before 3 PM to minimize insomnia risk. 1

• Bupropion has activating properties that can disrupt sleep if taken late in the day 1
• This timing strategy is particularly important given that insomnia is one of the most common adverse effects 3

Absolute Contraindications

Bupropion SR is absolutely contraindicated in patients with seizure disorders, current or prior eating disorders (bulimia or anorexia nervosa), and those abruptly discontinuing alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. 4

• The seizure risk at 300 mg/day is approximately 0.1% (1 in 1,000), but increases substantially with higher doses or in the presence of risk factors 3
• Eating disorders significantly increase seizure risk due to electrolyte abnormalities and metabolic changes 4
• Abrupt discontinuation of CNS depressants lowers seizure threshold acutely 4
• Do not use within 14 days of MAOI discontinuation due to hypertensive crisis risk 4

Dose Adjustments for Hepatic Impairment

For moderate to severe hepatic impairment, reduce the dose to 150 mg every other day (not daily). 1, 4

• Bupropion undergoes extensive hepatic metabolism, and impaired clearance leads to drug accumulation 1
• For mild hepatic impairment, consider reducing the dose and/or frequency, though specific recommendations are less defined 4
• The maximum dose should not exceed 150 mg every other day in moderate to severe impairment 1

Dose Adjustments for Renal Impairment

For moderate to severe renal impairment (GFR <90 mL/min), reduce the total daily dose by 50%. 1

• Bupropion and its active metabolites are cleared renally and accumulate in renal dysfunction 1
• This means a patient on 300 mg/day should be reduced to 150 mg/day 1
• Close monitoring for adverse effects is essential as metabolites may still accumulate 1

Efficacy Assessment Timeline

Allow 6-8 weeks at an adequate therapeutic dose before determining treatment response, but begin monitoring for adverse effects and suicidal ideation within 1-2 weeks. 1

• Early monitoring (1-2 weeks) focuses on safety, particularly neuropsychiatric symptoms and suicidal thoughts in patients under 24 years 1
• The risk for suicide attempts is greatest during the first 1-2 months of treatment 1
• If no adequate response by 6-8 weeks at therapeutic doses, modify the treatment approach rather than waiting longer 1

Special Populations: Older Adults

For older adults, start with 37.5 mg every morning, then gradually increase by 37.5 mg every 3 days as tolerated, with a maximum dose of 300 mg/day (150 mg twice daily). 1

• Lower starting doses reduce the risk of adverse reactions in this population 1
• The slower titration schedule (every 3 days vs. immediate increase) allows better tolerability assessment 1
• Maintain the same timing rule: second dose before 3 PM 1

Monitoring Parameters

Monitor blood pressure and heart rate periodically, especially during the first 12 weeks, as bupropion can elevate both parameters. 1

• Uncontrolled hypertension is a contraindication to bupropion use 1
• Screen for and monitor neuropsychiatric adverse effects including agitation, anxiety, mood changes, and suicidal ideation 1
• Patients under 24 years require particularly close monitoring due to increased suicide risk with all antidepressants 4

Common Pitfalls to Avoid

• Never exceed 300 mg/day for smoking cessation to maintain seizure risk at 0.1% 1
• Do not use bupropion SR interchangeably with XL formulation without dose adjustment, as they have different pharmacokinetics and maximum doses (SR max: 400 mg/day; XL max: 450 mg/day) 1
• Screen carefully for eating disorders as patients may not volunteer this history, and it represents an absolute contraindication 4
• Verify no concurrent opioid use if considering naltrexone-bupropion combination products, as naltrexone will precipitate withdrawal 5

Clinical Advantages

Bupropion SR offers distinct advantages including significantly lower rates of sexual dysfunction compared to SSRIs, minimal weight gain or even weight loss, and lower rates of sedation, making it particularly suitable for patients with depression characterized by low energy, apathy, or hypersomnia. 1