How to taper off sertraline (selective serotonin reuptake inhibitor) 100 mg daily and initiate bupropion (dopamine and norepinephrine reuptake inhibitor) therapy?

Tapering Sertraline and Initiating Bupropion Therapy

When switching from sertraline 100 mg to bupropion, implement a gradual sertraline taper over 4-8 weeks while cross-titrating with bupropion starting at 150 mg daily for 1 week, then increasing to 300 mg daily if tolerated.

Sertraline Tapering Protocol

Sertraline should be tapered slowly to minimize withdrawal symptoms, which can include dizziness, fatigue, headaches, nausea, sensory disturbances, anxiety, irritability, and insomnia 1:

• Week 1-2: Reduce sertraline from 100 mg to 75 mg daily
• Week 3-4: Reduce to 50 mg daily
• Week 5-6: Reduce to 25 mg daily
• Week 7-8: Reduce to 12.5 mg daily (half of the lowest available tablet)
• Then discontinue

Key considerations for sertraline tapering:

• Slower tapering is preferred over the traditional 2-4 week tapers recommended in older guidelines 1
• Hyperbolic tapering (progressively smaller dose reductions) minimizes withdrawal symptoms 1
• If withdrawal symptoms occur at any step, slow the taper by maintaining the current dose longer before proceeding

Bupropion Initiation Protocol

Begin bupropion while tapering sertraline:

• Start with bupropion 150 mg once daily for 1 week
• If tolerated, increase to 300 mg daily (either as 150 mg twice daily or 300 mg XL once daily) 2
• The optimal timing for initiating bupropion is when sertraline has been reduced to 50 mg daily

Key considerations for bupropion initiation:

• Morning dosing is preferred to minimize insomnia 3
• If using twice-daily dosing, administer the second dose before 3 PM to reduce insomnia risk 3
• Target dose is typically 300 mg daily for depression treatment 2

Monitoring During Transition

Monitor closely for:

1. Serotonin syndrome: Although rare with this combination, symptoms include mental status changes, autonomic instability, neuromuscular symptoms, and gastrointestinal symptoms 4, 5

2. Withdrawal symptoms: Dizziness, sensory disturbances, anxiety, irritability, and insomnia 1

3. Efficacy: Assess for improvement in depressive symptoms during and after the transition 6

4. Side effects of bupropion: Headache, dry mouth, insomnia, nausea, and agitation 2, 7

Special Considerations

• Seizure risk: Bupropion carries a 0.1% seizure risk. Discontinue immediately if seizures occur 3

• Anxiety: If the patient has significant anxiety, the transition may temporarily worsen anxiety symptoms as sertraline (which often helps anxiety) is reduced 4

• Sexual function: One benefit of this transition is that bupropion is less likely to cause sexual dysfunction compared to sertraline 6, 7

• Drug interactions: Avoid using this combination with MAOIs due to risk of serotonin syndrome 4

• Suicidality: Monitor closely for suicidal thoughts, especially in patients under 24 years of age 4

This approach balances the need to minimize withdrawal symptoms from sertraline while allowing adequate time for bupropion to reach therapeutic levels. Studies have shown that cross-titration is generally well-tolerated and can maintain antidepressant efficacy during the transition 6.