Starting Wellbutrin While Tapering Off Prozac
Yes, you can start taking Wellbutrin (bupropion) while tapering off Prozac (fluoxetine), but a cautious approach with appropriate monitoring is necessary to minimize risks.
Rationale for Cross-Tapering
- Fluoxetine (Prozac) has a very long half-life (2-3 days for parent compound, 7-9 days for active metabolite), which creates a natural tapering effect 1
- This pharmacokinetic property allows for a smoother transition when adding bupropion while reducing fluoxetine
- Cross-tapering can help maintain antidepressant coverage during the transition period, reducing risk of withdrawal symptoms or depression recurrence
Recommended Approach
Begin Wellbutrin at a low dose while still on Prozac:
- Start with Wellbutrin SR 100-150 mg once daily or Wellbutrin XL 150 mg once daily 1
- Maintain this starting dose for at least 7-14 days before increasing
Gradually taper Prozac:
- Due to its long half-life, Prozac can often be tapered more quickly than other SSRIs
- A common approach is to reduce by 50% every 1-2 weeks
- For example: 20mg → 10mg → discontinue
Gradually increase Wellbutrin dose:
- After 7-14 days, if well-tolerated, increase to target dose
- SR formulation: 100-150 mg twice daily (maximum 400 mg/day)
- XL formulation: 150-300 mg once daily (maximum 450 mg/day) 1
Monitoring Considerations
- Seizure risk: Bupropion can lower seizure threshold, especially at higher doses 2, 3
- Activation symptoms: Both medications can cause activation (anxiety, insomnia, agitation) which may be additive 1
- Drug interactions: Fluoxetine is a strong inhibitor of CYP2D6, which metabolizes bupropion, potentially increasing bupropion levels during cross-tapering
Important Precautions
- Timing of doses: To minimize insomnia risk, take the second dose of Wellbutrin SR before 3 PM 1
- Avoid rapid increases: Increasing bupropion too quickly increases seizure risk 2
- Monitor for serotonin syndrome: Although rare with this combination, be aware of symptoms like agitation, tremor, hyperthermia, or muscle rigidity
- Avoid benzodiazepines: If possible, avoid concurrent benzodiazepine use during this transition as they can mask withdrawal symptoms and create dependence issues 4
When to Seek Medical Help
- Development of severe anxiety, agitation, or suicidal thoughts
- Seizure activity
- Symptoms of serotonin syndrome
- Intolerable side effects that don't resolve within a few days
Evidence of Effectiveness
Research shows approximately 60% of patients with fluoxetine-resistant depression experienced full or partial response when switched to bupropion SR 5, making this a potentially effective strategy for those who haven't responded adequately to Prozac.
Remember that while this cross-tapering approach is generally safe and effective, individual responses may vary, and close monitoring during the transition period is essential.