What is the recommended protocol for tapering off fluoxetine (Prozac) to initiate bupropion (Wellbutrin) therapy?

Tapering Fluoxetine (Prozac) to Begin Bupropion (Wellbutrin) Therapy

Fluoxetine can be discontinued without a taper before starting bupropion due to its very long half-life, which naturally creates a self-tapering effect. 1

Understanding Medication Properties

Fluoxetine (Prozac)

• Very long half-life (2-3 days for parent compound, 7-9 days for active metabolite)
• Self-tapering effect due to extended elimination time
• Activating SSRI that may take weeks for side effects to manifest or resolve 1

Bupropion (Wellbutrin)

• Activating antidepressant that can rapidly improve energy levels
• Should not be used in agitated patients or those with seizure disorders
• Initial dosage: 37.5 mg every morning, then increase by 37.5 mg every 3 days
• Maximum dosage: 150 mg twice daily 1
• Second dose should be given before 3 p.m. to minimize insomnia risk 1

Transition Protocol

Step 1: Discontinuation of Fluoxetine

• Unlike other antidepressants, fluoxetine generally doesn't require a gradual taper due to its long half-life
• The medication naturally tapers itself as it slowly leaves the body over weeks 2
• This creates a natural buffer against withdrawal symptoms

Step 2: Washout Period

• Allow 1-2 weeks after stopping fluoxetine before starting bupropion
• This helps minimize potential drug interactions while maintaining antidepressant coverage due to fluoxetine's extended half-life

Step 3: Initiation of Bupropion

• Start with 37.5 mg every morning
• Increase by 37.5 mg every 3 days as tolerated
• Target dose: 150 mg twice daily (morning and early afternoon) 1
• Second dose should be given before 3 p.m. to minimize insomnia

Special Considerations

Monitoring for Withdrawal Symptoms

• Despite fluoxetine's self-tapering effect, monitor for potential withdrawal symptoms:
  • Somatic: dizziness, nausea, fatigue, sensory disturbances
  • Psychological: anxiety, irritability, mood changes 2
• If significant withdrawal symptoms occur, consider reinstating a small dose of fluoxetine and attempting a slower transition

Potential Side Effects During Transition

• Increased activation/energy (both medications have activating properties)
• Sleep disturbances (particularly with bupropion's second daily dose)
• Anxiety or agitation
• Gastrointestinal effects

Contraindications for Bupropion

• Seizure disorders
• Agitated patients
• Eating disorders
• Current use of MAO inhibitors 1

Common Pitfalls to Avoid

1. Starting bupropion too soon: While fluoxetine has a long half-life, starting bupropion immediately after stopping fluoxetine may increase the risk of side effects.

2. Dosing bupropion too late in the day: Taking the second dose after 3 p.m. can significantly increase the risk of insomnia 1.

3. Misinterpreting withdrawal symptoms: Symptoms that emerge during transition may be mistaken for relapse of depression rather than withdrawal effects 2.

4. Overlooking activation potential: Both medications have activating properties, which may temporarily increase anxiety or agitation during transition.