What is the optimal medication adjustment and fluoxetine (Prozac) taper for a 47‑year‑old woman with suicidal ideation, anxiety, and depression who is taking fluoxetine 30 mg at 5 pm and wants to switch to bupropion (Wellbutrin) 150 mg at bedtime but is experiencing insomnia and is also using eszopiclone (Lunesta) 1 mg at night?

Optimal Medication Adjustment Strategy

Switch Prozac (fluoxetine) 30 mg to morning dosing immediately, move Wellbutrin (bupropion) 150 mg to morning administration, and taper fluoxetine over 2–4 weeks while maintaining bupropion at therapeutic doses. 1

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Immediate Medication Timing Adjustments

Move Bupropion to Morning Dosing

• Administer bupropion 150 mg in the morning (not at bedtime) to eliminate insomnia, as the drug has activating properties that directly cause sleep disturbance when taken late in the day 1
• If using bupropion SR formulation and planning to increase to 300 mg daily, give the second 150 mg dose before 3 PM to minimize insomnia risk 1
• This single timing change will likely resolve the current insomnia problem without requiring Lunesta 1

Adjust Fluoxetine Timing

• Move fluoxetine 30 mg from 5 PM to morning administration to reduce evening activation and improve sleep 2
• Fluoxetine's long half-life (4–6 days) means timing changes take 1–2 weeks to show full effect 1

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Fluoxetine Taper Protocol

No Washout Required

• Begin bupropion immediately without waiting for fluoxetine washout, as neither drug is an MAOI and no dangerous interaction exists 1
• The combination of fluoxetine and bupropion is safe and well-established for treatment-resistant depression 1

Gradual Taper Schedule

• Week 1–2: Continue fluoxetine 30 mg daily (now in morning) + bupropion 150 mg morning
• Week 3–4: Reduce fluoxetine to 20 mg daily + bupropion 150 mg morning
• Week 5–6: Reduce fluoxetine to 10 mg daily + bupropion 150 mg morning
• Week 7: Discontinue fluoxetine; continue bupropion 150 mg morning 1

Rationale for Slow Taper

• Fluoxetine's extended half-life provides built-in protection against withdrawal, but gradual reduction minimizes risk of discontinuation syndrome 3
• If moderate-to-severe withdrawal symptoms emerge (anxiety, irritability, mood instability), pause the taper at the current dose for 1–2 weeks before resuming 1

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Bupropion Dose Optimization

Target Therapeutic Dose

• After fluoxetine is fully tapered, increase bupropion to 300 mg daily (150 mg twice daily for SR formulation, with second dose before 3 PM) 1
• The 300 mg dose provides superior antidepressant efficacy compared to 150 mg while maintaining seizure risk at 0.1% 1
• Wait 6–8 weeks at 300 mg daily before assessing treatment adequacy 1

Titration Schedule

• Start with 150 mg once daily in morning for 3 days
• Increase to 150 mg twice daily (morning and early afternoon) if tolerated 1
• Maximum dose is 450 mg/day, but 300 mg/day is standard for depression 1

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Eszopiclone (Lunesta) Management

Discontinue Lunesta After Timing Changes

• Once bupropion is moved to morning dosing, attempt to discontinue Lunesta 1 mg, as the insomnia is iatrogenic from nighttime bupropion administration 2
• If insomnia persists after medication timing adjustments, consider trazodone 25–100 mg at bedtime as a safer long-term alternative to eszopiclone 2
• Trazodone is safe when combined with bupropion and addresses insomnia without the dependence risk of eszopiclone 1

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Critical Safety Monitoring

Suicidal Ideation Surveillance

• Assess for suicidal ideation, agitation, irritability, and behavioral changes during weeks 1–2 of any medication adjustment, as suicide risk peaks in the first 1–2 months of antidepressant treatment 3, 4
• This 47-year-old patient with current suicidal ideation requires weekly monitoring for the first month 3
• Insomnia severity independently predicts suicidal ideation during depression treatment, making resolution of sleep disturbance a safety priority 5

Seizure Risk Screening

• Confirm absence of seizure history, eating disorders (bulimia/anorexia), head trauma, brain lesions, or alcohol/benzodiazepine withdrawal before continuing bupropion 1
• At 300 mg/day, seizure risk is approximately 0.1% (1 in 1,000) 1

Blood Pressure Monitoring

• Measure blood pressure at baseline and periodically during the first 12 weeks, as bupropion can elevate blood pressure 1
• Uncontrolled hypertension is a contraindication to bupropion 1

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Expected Timeline and Outcomes

Insomnia Resolution

• Insomnia should improve within 3–7 days after moving bupropion to morning dosing 1
• If sleep does not normalize, add trazodone 25–100 mg at bedtime rather than continuing eszopiclone 2

Antidepressant Response

• Full antidepressant effect requires 6–8 weeks at therapeutic bupropion doses (300 mg/day) 1
• Energy and motivation may improve within 2–4 weeks, but complete remission takes longer 1
• Approximately 42–49% of patients achieve remission with bupropion monotherapy 1

If Inadequate Response at 8 Weeks

• Add an SSRI (e.g., sertraline 50–200 mg daily or escitalopram 10–20 mg daily) rather than switching agents, as augmentation is equally effective as switching but avoids discontinuation symptoms 1
• Bupropion + SSRI combination has lower discontinuation rates (12.5%) than other augmentation strategies (20.6%) 1

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Common Pitfalls to Avoid

• Do not continue bedtime bupropion dosing—this is the direct cause of insomnia and must be corrected immediately 1
• Do not abruptly stop fluoxetine—taper over 2–4 weeks to minimize withdrawal symptoms 3
• Do not skip the intensive monitoring window in weeks 1–2—this period carries the highest suicide risk 3, 4
• Do not exceed 450 mg/day total bupropion dose—seizure risk increases markedly above this threshold 1
• Do not combine bupropion with MAOIs or initiate within 14 days of MAOI discontinuation 1