Tapering Duloxetine 90mg Before Starting Wellbutrin
Taper duloxetine gradually over at least 2 weeks by reducing the dose to 60mg daily for 1 week, then 30mg daily for 1 week before discontinuation, then wait at least 3-5 days before initiating bupropion at 150mg daily.
Rationale for Gradual Duloxetine Taper
Abrupt discontinuation of duloxetine causes significant withdrawal symptoms. Research demonstrates that 44.3% of duloxetine-treated patients experience discontinuation-emergent adverse events (DEAEs) when stopped abruptly, compared to only 22.9% with placebo 1. The most common withdrawal symptoms include:
- Dizziness (12.4%) - the most frequent symptom
- Nausea (5.9%)
- Headache (5.3%)
- Paresthesias (2.9%)
- Irritability (2.4%)
- Nightmares (2.0%)
Among patients experiencing withdrawal symptoms, the average number of symptoms is 2.4, with most rated as mild to moderate severity 1. Importantly, 65% of symptoms resolve within 7 days, but this requires proper tapering.
Specific Tapering Schedule from 90mg
Since 90mg exceeds the standard maximum dose of 60mg daily 2, and higher doses are associated with more withdrawal symptoms 1:
Week 1: Reduce to 60mg once daily
Week 2: Reduce to 30mg once daily
Week 3: Discontinue duloxetine
Days 1-5 after discontinuation: Washout period
Day 6 onwards: Initiate bupropion
Critical Warning About Alternate-Day Dosing
Never use alternate-day dosing when tapering duloxetine. Recent pharmacokinetic modeling demonstrates that dosing every other day causes pronounced fluctuations in receptor occupancy, significantly increasing withdrawal symptom risk 3. This applies even at minimum therapeutic doses and cannot be recommended as a safe tapering strategy 3.
Initiating Bupropion After Duloxetine
Once duloxetine is discontinued and the brief washout period completed, start bupropion using the FDA-approved schedule 4:
- Days 1-3: 150mg once daily
- Day 4 onwards: 150mg twice daily (if tolerated)
- Maximum dose: 300mg per day
The initial 150mg once-daily dosing for 3 days allows assessment of tolerability before increasing 4. There is no pharmacological interaction requiring extended washout between duloxetine and bupropion, but the 3-5 day gap allows duloxetine withdrawal symptoms to emerge and be managed before introducing a new medication.
Monitoring During Transition
Closely monitor during weeks 1-2 of bupropion initiation for:
- Worsening depression or suicidal ideation (FDA black box warning for all antidepressants) 4
- Seizure risk factors (bupropion is contraindicated with seizure history, brain metastases) 5
- Neuropsychiatric symptoms (agitation, irritability, unusual behavior changes)
Assessment should occur within 1-2 weeks of starting bupropion, then regularly thereafter 6.
Common Pitfall to Avoid
The most dangerous error is attempting to "cross-taper" by starting bupropion while still on duloxetine. While guidelines mention bupropion can be used alongside other antidepressants 7, this applies to established therapy, not during active discontinuation when withdrawal symptoms complicate the clinical picture. Complete the duloxetine taper first, allow a brief washout, then initiate bupropion as monotherapy.
Special Considerations
If the patient has renal impairment, use an even slower duloxetine taper with lower starting doses 2. For geriatric patients, consider extending each taper step to 2 weeks rather than 1 week, as they tolerate medication changes less well 8.
If severe withdrawal symptoms emerge during tapering, temporarily return to the previous dose for 3-5 days before attempting a slower reduction. The goal is minimizing morbidity during the transition, not adhering rigidly to a predetermined schedule.