What dose of Bupropion should be started and what dose should Sertraline be decreased to when cross-titrating from 125 mg of Sertraline?

Cross-Titration from Sertraline to Bupropion

Start bupropion SR at 150 mg once daily in the morning for 3 days, then increase to 150 mg twice daily (with second dose before 3 PM), while simultaneously reducing sertraline from 125 mg to 100 mg initially, then tapering by 25-50 mg every 1-2 weeks as tolerated. 1

Initial Bupropion Dosing Strategy

• Begin with bupropion SR 150 mg once daily in the morning for the first 3 days, then advance to the standard therapeutic dose of 150 mg twice daily (300 mg total daily) if tolerated 1
• The morning timing leverages bupropion's activating properties, which can improve energy levels and reduce apathy 1
• Administer the second dose before 3 PM to minimize insomnia risk, a critical consideration when cross-titrating with another antidepressant 1
• This gradual titration minimizes seizure risk while achieving therapeutic levels 1

Alternative Conservative Approach for High-Risk Patients

• If the patient has multiple comorbidities, is elderly, or is on multiple psychotropic medications, consider starting at 37.5 mg every morning and increasing by 37.5 mg every 3 days as tolerated, with a target of 150 mg twice daily 1
• This more conservative approach allows better assessment of tolerability in complex patients 1

Sertraline Tapering Protocol

• Reduce sertraline from 125 mg to 100 mg when initiating bupropion, allowing both medications to be on board during the transition 2
• After 1-2 weeks at the therapeutic bupropion dose (300 mg/day), further reduce sertraline by 25-50 mg increments every 1-2 weeks 2
• The evidence suggests that sertraline does not demonstrate a clear dose-response curve in depression treatment, supporting that lower doses maintain efficacy during tapering 2
• Complete sertraline discontinuation typically occurs over 4-6 weeks total to minimize withdrawal symptoms

Rationale for Combination Therapy During Transition

• The combination of bupropion and sertraline addresses depression through complementary mechanisms: sertraline affects serotonin while bupropion works via noradrenergic/dopaminergic pathways 1
• Bupropion is the only antidepressant with no appreciable activity on serotonin, making it mechanistically distinct and suitable for combination 3
• Evidence supports that combinations of serotonergic agents and bupropion can convert partial response to full response in treatment-resistant depression 4

Monitoring and Safety Considerations

• Watch for increased agitation during the first 2-4 weeks, as bupropion is an activating medication 1
• Monitor for neuropsychiatric adverse effects, particularly if the patient is younger than 24 years 1
• The maximum bupropion SR dose should not exceed 400 mg per day to minimize seizure risk (0.1% at doses ≤300 mg/day, increasing at higher doses) 1, 3, 5
• Assess blood pressure regularly, as bupropion should be avoided in patients with uncontrolled hypertension 1

Expected Timeline for Clinical Response

• Bupropion's onset of action is typically 2 weeks with full efficacy attained at 4 weeks of treatment 3
• If no response is seen after 6-8 weeks at an adequate dose, consider alternative treatment strategies 1
• The therapeutic window allows for gradual sertraline discontinuation while bupropion reaches steady-state levels

Key Contraindications and Precautions

• Absolutely contraindicate bupropion in patients with seizure disorders, eating disorders (bulimia/anorexia), or those taking MAOIs (or within 14 days of discontinuing MAOIs) 1
• For patients with moderate to severe hepatic impairment, do not exceed 150 mg daily total 1
• For moderate to severe renal impairment (GFR <90 mL/min), reduce the total daily dose by half 1

Advantages of This Cross-Titration Approach

• Bupropion may be particularly beneficial if the patient has comorbid low energy, apathy, or sexual dysfunction from sertraline 1, 6
• Sexual dysfunction occurs in 63% of men and 41% of women on sertraline compared to only 15% of men and 7% of women on bupropion 6
• The overlapping period provides continuity of antidepressant coverage, reducing risk of depressive relapse during the transition 4