Switching from Lexapro (Escitalopram) to Zoloft (Sertraline)
Use a gradual cross-taper over 1-2 weeks: reduce escitalopram by 50% while simultaneously starting sertraline at 25-50 mg daily, then discontinue escitalopram after one week while continuing sertraline. 1
Cross-Taper Protocol
The recommended approach involves overlapping the medications rather than abrupt discontinuation:
- Week 1: Reduce escitalopram to 50% of current dose AND start sertraline 25-50 mg daily 1
- Week 2: Discontinue escitalopram completely while continuing sertraline 1
- Subsequent weeks: Titrate sertraline upward as needed (typical range 50-200 mg daily) 2
This gradual cross-titration strategy is informed by the half-life and receptor profiles of each medication 2. Both escitalopram and sertraline are SSRIs with similar mechanisms, making direct switching relatively straightforward compared to switches between different antidepressant classes 3.
Critical Safety Monitoring
Monitor intensively for serotonin syndrome during the overlap period, especially in the first 24-48 hours after initiating the cross-taper. 2, 1 Watch for:
- Tremor, diarrhea, and sweating 2
- Neuromuscular rigidity and hyperthermia 1
- Agitation, confusion, and delirium 2
While both medications are SSRIs and the risk is lower than switching between different drug classes, vigilance remains essential during any period of overlapping serotonergic medications 2.
Discontinuation Syndrome Prevention
Escitalopram carries risk for discontinuation syndrome, particularly at higher doses 4. Common withdrawal symptoms include:
- Dizziness (44% of patients), muscle tension, and chills 4
- Confusion, trouble concentrating, and amnesia 4
- Emotional lability and crying 4
The cross-taper approach significantly reduces discontinuation syndrome risk compared to abrupt cessation. 2, 3 Patients on higher escitalopram doses or with lower drug clearance face increased discontinuation risk and may benefit from an even more gradual taper extending to 2-3 weeks 4.
Follow-Up Schedule
- Week 1-2: Contact patient (telephone or in-person) to assess tolerability and adherence during cross-taper 2, 1
- Week 2-3: Schedule follow-up visit after completing the switch to evaluate therapeutic response and adverse effects 1
- Ongoing: Continue monitoring at regular intervals, as sertraline may require dose adjustments up to 200 mg daily for optimal response 2
Comparative Efficacy Considerations
Both medications demonstrate similar efficacy for major depressive disorder 5. In head-to-head trials, escitalopram 10 mg daily showed equivalent efficacy to sertraline flexibly dosed 50-200 mg daily (mean 144 mg), with 75% vs 70% response rates respectively 5.
Sertraline offers advantages in drug interaction profile compared to escitalopram, with less effect on cytochrome P450 metabolism 2, 6. This makes sertraline preferable when patients take multiple medications metabolized through hepatic pathways 2.
Special Population Adjustments
For elderly patients or those with hepatic impairment: Extend the cross-taper to 2-3 weeks, use lower starting doses, and monitor more frequently 1. Consider starting sertraline at 25 mg daily rather than 50 mg 2.
For patients on higher escitalopram doses (>10 mg): Consider a more gradual taper with smaller dose reductions (e.g., 25% decrements over 2-3 weeks) to minimize discontinuation symptoms 4.
Common Pitfalls to Avoid
- Never abruptly discontinue escitalopram without tapering, as this significantly increases discontinuation syndrome risk 2, 3, 4
- Avoid combining with MAOIs or other serotonergic agents during the transition period beyond the planned cross-taper 2
- Do not assume all SSRIs are interchangeable - while both are SSRIs, individual patient response and tolerability can vary 6
- Monitor adherence closely - patients may discontinue one medication without starting the other, leading to symptom recurrence 2