Switching from Sertraline 100mg to Atomoxetine
Taper sertraline 100mg down over 10-14 days to minimize withdrawal symptoms, then start atomoxetine at a low dose after sertraline discontinuation, with close monitoring during the first few weeks of atomoxetine treatment.
Sertraline Discontinuation Strategy
Gradual tapering is essential because sertraline is associated with discontinuation syndrome, characterized by dizziness, fatigue, nausea, insomnia, sensory disturbances, anxiety, and irritability 1.
- Taper sertraline over 10-14 days to limit withdrawal symptoms 1
- Sertraline has been specifically identified as one of the SSRIs with higher risk of discontinuation syndrome (along with paroxetine and fluvoxamine) 1
- Withdrawal symptoms typically appear within 2 weeks of discontinuation and can occur after prolonged use 2
- Risk factors for more severe withdrawal include longer treatment duration, higher doses, and abrupt cessation 2
Suggested Sertraline Taper Schedule:
- Days 1-4: Reduce to 75mg daily
- Days 5-8: Reduce to 50mg daily
- Days 9-12: Reduce to 25mg daily
- Days 13-14: Discontinue completely
Atomoxetine Initiation
Start atomoxetine after completing the sertraline taper - there is no required washout period between these medications as they have different mechanisms of action and no significant drug interaction concerns.
Important Drug Interaction Consideration:
Sertraline can elevate atomoxetine levels because sertraline inhibits CYP2D6, the primary metabolic pathway for atomoxetine 1. This interaction is similar to what occurs with paroxetine and can result in:
- Greater atomoxetine exposure
- Slower elimination
- Increased risk of adverse effects 3
Therefore, starting atomoxetine after sertraline is fully discontinued avoids this interaction.
Atomoxetine Starting Protocol
Begin with low-dose atomoxetine using weight-based dosing 1:
- Initial dose: 40mg once daily (or approximately 0.5 mg/kg/day for patients <70kg)
- After 3-7 days: Increase to target dose of approximately 80mg daily (or 1.2 mg/kg/day)
- Maximum dose: 100mg/day or 1.4 mg/kg/day, whichever is lower 1
- Can be administered as single morning dose or divided into two doses 3, 4
Critical Monitoring Requirements
Close monitoring is mandatory during the first few weeks of atomoxetine treatment 1:
Monitor for:
- Suicidal ideation and behavior - atomoxetine carries a black-box warning for increased suicidal thinking, particularly in the first few months of treatment or with dose changes 1, 3
- Clinical worsening and unusual behavioral changes 1
- Cardiovascular effects - modest increases in heart rate and blood pressure 3, 4
- Hepatotoxicity - rare but serious liver injury has been reported 3
Common Adverse Effects to Anticipate:
- Nausea, decreased appetite, abdominal pain 1, 3
- Headache, somnolence, fatigue 3
- These are typically mild to moderate and may be reduced by slower titration 3
Timeline Summary
Total switching period: 2-3 weeks
- Week 1-2: Taper sertraline over 10-14 days
- Week 2-3: Start atomoxetine at 40mg daily after sertraline completion
- Week 3+: Increase atomoxetine to target dose of 80-100mg daily as tolerated
- Ongoing: Monitor closely for adverse effects, especially suicidality, during first 8-12 weeks 1
Key Clinical Pitfalls to Avoid
- Do not start atomoxetine while still on sertraline - the CYP2D6 inhibition by sertraline will significantly increase atomoxetine levels and adverse effects 1
- Do not abruptly stop sertraline - this increases risk of severe discontinuation syndrome 1, 2
- Do not start atomoxetine at high doses - begin low and titrate to minimize adverse effects 1
- Do not neglect suicide risk monitoring - this is a regulatory requirement with atomoxetine, especially during initiation and dose changes 1, 3