What is the recommended protocol for switching from Lexapro (escitalopram) to Sertraline (sertraline)?

Switching from Lexapro (Escitalopram) to Sertraline

When switching from escitalopram to sertraline, perform a direct cross-taper over 1-2 weeks: gradually reduce escitalopram while simultaneously initiating sertraline at a low dose, then titrate sertraline upward as escitalopram is discontinued. This approach minimizes both withdrawal symptoms and periods without antidepressant coverage.

Switching Strategy

Direct Cross-Taper Approach (Recommended)

• Start sertraline at 25-50 mg/day while beginning to taper escitalopram 1
• Reduce escitalopram by 50% (e.g., from 10 mg to 5 mg) for 3-7 days while maintaining the initial sertraline dose 1
• Discontinue escitalopram completely after 3-7 days at the reduced dose 1
• Increase sertraline to target dose (50-200 mg/day) over the following week as tolerated 1

This cross-taper method is preferred because both medications are SSRIs with similar mechanisms, making concurrent use relatively safe while avoiding treatment gaps that could lead to depressive relapse 2.

Rationale for Cross-Tapering

• Escitalopram has a moderate half-life requiring gradual discontinuation to prevent withdrawal symptoms 3
• Abrupt discontinuation increases risk of antidepressant discontinuation syndrome (ADS), which occurs frequently and includes dizziness, muscle tension, chills, confusion, and emotional symptoms 3
• Higher doses of escitalopram carry greater risk of withdrawal symptoms, making tapering essential 3
• Gradual dose reduction over 10-14 days limits withdrawal symptoms 1

Monitoring During the Switch

Week 1-2 (Active Switching Period)

• Monitor closely for withdrawal symptoms: dizziness (44% incidence), muscle tension (44%), chills (44%), confusion (40%), and emotional lability 3
• Watch for adverse events from sertraline initiation: gastrointestinal symptoms, insomnia, nervousness, and tremors are common SSRI side effects 1
• Contact should occur within the first week (in-person or telephone) to assess tolerability and adherence 1

Weeks 3-8 (Stabilization Period)

• Assess response to sertraline at 4-6 weeks after reaching therapeutic dose 1
• Target dose range for sertraline is 50-200 mg/day, with most patients responding to 50-150 mg/day 1
• Monitor for treatment response and adverse events through regular follow-up 1

Critical Safety Considerations

Avoid These Pitfalls

• Never combine SSRIs with MAOIs - both escitalopram and sertraline are contraindicated with monoamine oxidase inhibitors 1
• Do not start sertraline at high doses - higher starting doses increase risk of behavioral activation and suicide-related events, particularly in adolescents and young adults 1
• Do not abruptly discontinue escitalopram - this significantly increases withdrawal symptom severity 3

Drug Interaction Awareness

• Sertraline has less effect on metabolism of other medications compared to other SSRIs, making it a favorable choice when drug interactions are a concern 1
• Both medications can cause drug interactions through cytochrome P450 inhibition, though sertraline is generally better tolerated in this regard 1

Expected Outcomes

Efficacy Considerations

• No significant efficacy differences exist between escitalopram and sertraline - both are effective first-line treatments for major depressive disorder 1, 4
• Response rates are comparable: approximately 70-75% of patients respond to either medication at therapeutic doses 4
• Switching between SSRIs shows similar outcomes to continuing the same medication when done appropriately 1

Tolerability Profile

• Both medications are generally well tolerated with low discontinuation rates due to adverse events (2-4%) 4
• Sertraline may have slightly better tolerability in some patients due to fewer drug interactions 1
• Individual patient factors should guide the choice if tolerability issues emerge during the switch 5

Timeline Summary

• Days 1-7: Reduce escitalopram to 50% of dose while starting sertraline 25-50 mg
• Days 8-14: Discontinue escitalopram, maintain or increase sertraline
• Weeks 3-4: Titrate sertraline to therapeutic dose (typically 50-150 mg)
• Weeks 4-8: Assess full therapeutic response

This conservative cross-taper approach balances the need to avoid withdrawal symptoms while minimizing the risk of depressive symptom exacerbation during the transition 2, 6.