What is the recommended dosing schedule for bupropion (75 mg) when initiating treatment for depression and for smoking cessation?

Bupropion 75 mg Dosing Guidelines

Standard Dosing Protocols

Bupropion 75 mg is not a standard therapeutic dose for either depression or smoking cessation; the recommended starting dose is 150 mg once daily, which should be titrated to 150 mg twice daily (300 mg total) for therapeutic effect. 1

For Major Depressive Disorder

• Initial dosing: Start with bupropion SR 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily dose) if tolerated. 1
• Timing: Administer the first dose in the morning and the second dose before 3 PM to minimize insomnia risk. 1
• Maximum dose: Do not exceed 400 mg/day for SR formulation or 450 mg/day for XL formulation to maintain seizure risk at approximately 0.1%. 1
• Response assessment: Allow 6–8 weeks at therapeutic doses before determining treatment adequacy; early improvement in energy may occur within the first few weeks, but full antidepressant effects require the full duration. 1

For Smoking Cessation

• Standard regimen: Begin with 150 mg once daily for days 1–3, then increase to 150 mg twice daily (300 mg total) if tolerated. 1
• Timing of initiation: Start bupropion 1–2 weeks before the target quit date to establish therapeutic drug levels prior to cessation attempts. 1
• Maximum dose: The maximum dose for smoking cessation is 300 mg per day—do not exceed this to maintain seizure risk at 0.1%. 1
• Treatment duration: Continue for 7–12 weeks after the quit date, with formal efficacy assessment after this period. 1
• Combination therapy: Bupropion plus nicotine replacement therapy achieves the highest abstinence rates (35.5% at 12 months vs. 30.3% with bupropion alone), though the difference is not statistically significant. 1

Special Population Dosing Adjustments

Older Adults (≥55 years)

• Initial dose: Start with 37.5 mg once daily in the morning to minimize adverse reactions. 1, 2
• Titration: Increase by 37.5 mg every 3 days as tolerated. 1, 2
• Maximum dose: 150 mg twice daily (300 mg total daily dose). 1, 2
• Timing: Administer the second dose before 3 PM to prevent sleep disturbances. 1

Renal Impairment

• Moderate to severe impairment (GFR <90 mL/min): Reduce the total daily dose by 50%, as bupropion and its metabolites are cleared renally and may accumulate. 1, 2
• Monitoring: Close monitoring for adverse reactions is required due to drug accumulation. 1

Hepatic Impairment

• Moderate to severe impairment: The total daily dose should not exceed 150 mg daily (one tablet). 1
• Mild impairment: Consider dose reduction and/or frequency adjustment. 1

Absolute Contraindications

Screen for these conditions before prescribing—their presence prohibits bupropion use:

• Seizure disorders or conditions predisposing to seizures (history of seizures, brain tumor, stroke, head trauma, eating disorders such as bulimia or anorexia nervosa). 1, 2
• Current or recent MAOI use (within 14 days of discontinuation). 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs due to increased seizure risk. 1
• Uncontrolled hypertension requires blood pressure control before initiation. 1, 2
• Concurrent tamoxifen therapy (bupropion may reduce tamoxifen efficacy via CYP2D6 inhibition). 1, 2

Critical Monitoring Parameters

Early Treatment Phase (Weeks 1–2)

• Suicidal ideation: Monitor closely, especially in patients younger than 24 years, as the risk of suicide attempts is highest during the first 1–2 months of treatment. 1
• Neuropsychiatric symptoms: Assess for agitation, anxiety, irritability, or unusual behavioral changes. 1, 2
• Blood pressure and heart rate: Measure at baseline and periodically during the first 12 weeks, as bupropion can cause elevations in both parameters. 1, 2

Ongoing Monitoring

• Seizure risk factors: The seizure rate at 300 mg/day is approximately 0.1% (1 in 1,000 patients); risk increases with doses >450 mg/day or rapid dose escalation. 1, 3
• Weight and energy levels: Bupropion is associated with minimal weight gain or even weight loss and has activating properties that improve energy. 1
• Sexual function: Bupropion has significantly lower rates of sexual dysfunction compared to SSRIs. 1

Clinical Advantages and Special Considerations

• Dual benefit: Bupropion is particularly beneficial for patients with comorbid depression and smoking cessation needs, addressing both conditions simultaneously. 1
• Comorbid anxiety: Baseline anxiety does not diminish bupropion's comparative efficacy; comorbid anxiety does not modify treatment response. 1
• Depression with low energy: Bupropion may be especially useful for patients with depression characterized by low energy, apathy, or hypersomnia due to its activating properties. 1
• Weight management: Combining bupropion with naltrexone can help with smoking cessation while mitigating associated weight gain. 1

Common Pitfalls to Avoid

• Do not use 75 mg as a maintenance dose—this is subtherapeutic; titrate to at least 150 mg twice daily (300 mg total) for efficacy. 1
• Do not skip the 1–2 week lead time before the quit date for smoking cessation—therapeutic drug levels must be established first. 1
• Do not administer the second dose after 3 PM—this significantly increases insomnia risk. 1
• Do not exceed 300 mg/day for smoking cessation or 450 mg/day for depression—seizure risk rises markedly above these thresholds. 1
• Do not discontinue prematurely before 6–8 weeks unless significant adverse effects occur—full therapeutic effects require this duration. 1