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

Switching from Zoloft (Sertraline) to Lexapro (Escitalopram)

The recommended protocol for switching from Zoloft (sertraline) to Lexapro (escitalopram) is a gradual cross-tapering approach over 1-2 weeks, where Lexapro is initiated at 10 mg daily while gradually reducing Zoloft to minimize discontinuation symptoms and maintain therapeutic efficacy. 1, 2

Rationale for Switching

• Both medications are SSRIs with similar efficacy profiles but different side effect profiles
• Common reasons for switching include:
  • Inadequate response to Zoloft
  • Unacceptable side effects with Zoloft
  • Potential for fewer drug interactions with Lexapro (has less effect on CYP450 enzymes) 1

Cross-Tapering Protocol

Week 1:

• Start Lexapro at 10 mg daily (therapeutic starting dose)
• Reduce Zoloft to 50% of current dose
• Monitor for signs of serotonin syndrome or discontinuation symptoms

Week 2:

• Continue Lexapro at 10 mg daily
• Further reduce Zoloft to 25% of original dose for 3-4 days, then discontinue completely
• If patient was on high doses of Zoloft (>150 mg), consider extending the taper to 3 weeks

Week 3 and beyond:

• Continue Lexapro at 10 mg daily
• If needed and tolerated, Lexapro can be increased to 20 mg daily (maximum recommended dose) 3, 1

Monitoring During Switch

Watch for discontinuation symptoms:

• Dizziness (44% of patients)
• Muscle tension (44%)
• Chills (44%)
• Confusion or trouble concentrating (40%)
• Amnesia (28%)
• Emotional lability/crying (28%) 4

Watch for serotonin syndrome:

• Agitation
• Confusion
• Rapid heart rate
• Dilated pupils
• High blood pressure
• Hyperthermia
• Muscle rigidity
• Tremor 1

Special Considerations

1. Higher risk of discontinuation syndrome:

   • Patients on higher doses of Zoloft (>100 mg)
   • Patients who have been on Zoloft for longer periods (>6 months)
   • Consider slower tapering for these patients 1, 4

2. Hepatic impairment:

   • Both medications require dose adjustments
   • May need to reduce Lexapro starting dose to 5 mg daily 3, 1

3. Elderly patients:

   • Start with lower doses (5 mg Lexapro)
   • Extend cross-tapering period to 3-4 weeks 1

Evidence Supporting This Approach

Research shows that gradual discontinuation strategies result in better outcomes than abrupt switching. In one study, the relative risk of early discontinuation was 0.77 for the slowest dose reduction compared with more rapid strategies 5. Similarly, another study found that gradual antipsychotic discontinuation combined with immediate initiation of the new medication had the most favorable efficacy and tolerability profile 6.

Studies specifically examining escitalopram discontinuation syndrome found that higher doses and plasma concentrations of escitalopram were associated with increased risk of discontinuation symptoms, suggesting that very slow tapering is beneficial 4.

Advantages of This Approach

1. Minimizes risk of discontinuation syndrome
2. Maintains therapeutic coverage throughout the transition
3. Allows for early detection and management of potential adverse effects
4. Provides smooth transition between medications with similar mechanisms of action
5. Reduces risk of relapse during the switching period 2

This cross-tapering approach balances the need to minimize discontinuation symptoms while ensuring adequate therapeutic coverage during the transition between these two SSRIs.