How to cross-taper from 20mg Lexapro (escitalopram) to sertraline?

Cross-Tapering from Escitalopram 20mg to Sertraline

Start sertraline at 25 mg daily while simultaneously beginning a slow taper of escitalopram 20mg, reducing by 5mg every 1-2 weeks, then titrate sertraline upward only after escitalopram is discontinued or at very low doses (≤5mg). 1, 2

Critical Safety Warning

• Serotonin syndrome risk is the primary concern when combining TCAs or SSRIs with other serotonergic agents, with symptoms typically arising within 24-48 hours of combining medications 2
• Symptoms include mental status changes, neuromuscular hyperactivity (tremors, muscle twitching), autonomic hyperactivity (fever, sweating, rapid heart rate, diarrhea), and can be fatal if untreated 2
• Immediate discontinuation of all serotonergic agents is required if serotonin syndrome develops 2

Recommended Cross-Taper Protocol

Phase 1: Initiate Sertraline at Low Dose

• Start sertraline at 25 mg daily while patient remains on escitalopram 20mg 1, 3
• Monitor intensively for serotonin syndrome symptoms in the first 24-48 hours 2
• Maintain this combination for 3-7 days to assess tolerability 1

Phase 2: Begin Escitalopram Taper

• Reduce escitalopram by 5mg (to 15mg) after confirming sertraline tolerability 1
• Continue this dose for 1-2 weeks before next reduction 1, 4
• Taper escitalopram slowly: 20mg → 15mg → 10mg → 5mg → discontinue, with each step taking 1-2 weeks 1, 4
• Never use alternate-day dosing as this causes severe receptor occupancy fluctuations and withdrawal symptoms 5

Phase 3: Titrate Sertraline

• Wait until escitalopram is at ≤5mg or fully discontinued before increasing sertraline 2
• Increase sertraline in 25-50mg increments at 1-2 week intervals 1, 3
• Target therapeutic dose is typically 50mg daily, which is optimal for most patients 3
• Maximum dose is 200mg daily if needed, with increases at weekly intervals minimum 1, 3

Why This Approach

Slow hyperbolic tapering minimizes withdrawal symptoms by reducing receptor occupancy linearly rather than abruptly 4. Standard guideline recommendations of 2-4 week tapers show minimal benefit over abrupt discontinuation and are poorly tolerated 4. Tapering over months to very low doses (far below minimum therapeutic doses) has demonstrated greater success 4.

Starting sertraline at low dose (25mg) before completing the escitalopram taper allows for overlap while minimizing serotonin syndrome risk, as recommended for switching between serotonergic agents 1, 2. The 25mg starting dose is specifically recommended to reduce serotonin syndrome risk 2.

Monitoring Requirements

• Weekly contact (phone or in-person) during the first month 1
• Monthly follow-up thereafter until stable on sertraline 1
• Instruct patient to immediately report: confusion, agitation, tremors, fever, sweating, rapid heart rate, diarrhea, or muscle twitching 2
• Use adverse effects checklist at each visit 1

Common Pitfalls to Avoid

• Do NOT use alternate-day dosing when tapering escitalopram—this causes pronounced receptor occupancy variation and severe withdrawal effects even at low doses 5
• Do NOT rapidly taper escitalopram over 10-14 days as older guidelines suggest—this timeframe is inadequate for patients on long-term therapy 1, 4
• Do NOT increase sertraline to full therapeutic doses while escitalopram remains at higher doses (>5mg) due to serotonin syndrome risk 2
• Do NOT abruptly discontinue escitalopram—all SSRIs require slow tapering to prevent withdrawal effects 1, 6

Timeline Summary

• Total transition period: 6-10 weeks minimum
• Week 1: Start sertraline 25mg + escitalopram 20mg
• Week 2-3: Sertraline 25mg + escitalopram 15mg
• Week 4-5: Sertraline 25mg + escitalopram 10mg
• Week 6-7: Sertraline 25mg + escitalopram 5mg
• Week 8: Sertraline 25mg + discontinue escitalopram
• Week 9+: Increase sertraline to 50mg, then titrate as needed 1, 4, 3