What is the dose equivalency when converting a patient from Zoloft (sertraline) to Lexapro (escitalopram)?

Dose Equivalency: Sertraline (Zoloft) to Escitalopram (Lexapro)

When converting from sertraline to escitalopram, use a ratio of approximately 50 mg sertraline to 10 mg escitalopram, though clinical trials suggest these may represent equipotent doses rather than a strict mathematical conversion. 1, 2

Conversion Ratios Based on Evidence

Standard Dose Equivalencies

• Sertraline 50 mg ≈ Escitalopram 10 mg 1, 2
• Sertraline 100 mg ≈ Escitalopram 10-20 mg 2, 3
• Sertraline 150 mg ≈ Escitalopram 20 mg 2, 3

The most robust evidence comes from a head-to-head randomized controlled trial where escitalopram 10 mg/day (fixed dose) was compared to sertraline flexibly dosed 50-200 mg/day (mean 144 mg, median 150 mg), showing equivalent efficacy with 75% vs 70% response rates respectively. 2 This suggests that escitalopram 10 mg is roughly equivalent to sertraline 100-150 mg in clinical effectiveness.

Pharmacokinetic Considerations

• Therapeutic plasma concentrations differ substantially: sertraline achieves 10-50 ng/mL while escitalopram reaches 27-28 ng/mL at standard doses 4, 1
• Escitalopram has a longer half-life (27-33 hours) compared to sertraline's shorter half-life, which impacts switching strategies 5, 1
• Both medications exhibit linear, dose-proportional pharmacokinetics within their therapeutic ranges 5

Switching Strategy

Direct Switch Method (Preferred)

Perform a direct switch without tapering since both are SSRIs with similar mechanisms. 1 This approach minimizes the risk of symptom recurrence and is generally well-tolerated.

• Stop sertraline and start escitalopram the next day at the equivalent dose
• Use the 5:1 ratio as a starting point (e.g., sertraline 100 mg → escitalopram 10-20 mg)
• Monitor closely for the first 1-2 weeks for efficacy and tolerability

Cross-Taper Method (Alternative)

If the patient has a history of discontinuation symptoms or anxiety about medication changes:

• Begin escitalopram at target dose while maintaining current sertraline dose for 3-7 days
• Then discontinue sertraline abruptly (given escitalopram's coverage)
• This approach is particularly important given sertraline's shorter half-life and association with discontinuation syndrome 4, 1

Monitoring and Dose Adjustment

Initial Monitoring Period

• Week 1-2: Assess for discontinuation symptoms (dizziness, fatigue, paresthesias, anxiety, irritability) despite the direct switch 4, 1
• Week 2-4: Evaluate therapeutic response and tolerability at new dose
• Week 4-8: Optimize dosing if needed based on clinical response

Dose Titration Guidelines

• Escitalopram can be increased in 10 mg increments at 1-2 week intervals if response is inadequate 4
• Maximum dose: escitalopram 20 mg/day (equivalent to sertraline 150-200 mg/day based on trial data) 2, 3
• Important caveat: Escitalopram doses >40 mg/day are contraindicated due to QT prolongation risk 4

Clinical Considerations and Pitfalls

Drug Interaction Profile

Escitalopram has a more favorable drug interaction profile than sertraline. 4, 5

• Escitalopram has minimal CYP450 inhibition, particularly less effect on CYP2D6 compared to sertraline 4, 5
• Sertraline can interact with drugs metabolized by CYP2D6, while escitalopram is less likely to cause such interactions 4
• Both require caution with other serotonergic agents to avoid serotonin syndrome 4

Common Pitfalls to Avoid

• Do not use a 1:1 mg conversion (e.g., sertraline 100 mg to escitalopram 100 mg) - this would represent massive overdosing
• Watch for discontinuation syndrome even with direct switching, as sertraline has been specifically associated with this phenomenon 4, 1
• Monitor for initial anxiety/agitation in the first days after switching, as this can occur with SSRI initiation 4
• Avoid exceeding escitalopram 40 mg/day due to cardiac safety concerns with QT prolongation 4

Tolerability Expectations

Both medications are generally well-tolerated with low discontinuation rates (2% for escitalopram, 4% for sertraline in comparative trials). 2 Common side effects include nausea, dry mouth, drowsiness, and sexual dysfunction at equivalent doses. 1 Some evidence suggests escitalopram may have slightly fewer adverse effects (45% vs 56% reporting adverse experiences). 3