What is the best method for switching from Lexapro (escitalopram) to another Selective Serotonin Reuptake Inhibitor (SSRI)?

Switching from Lexapro (Escitalopram) to Another SSRI

All SSRIs should be slowly tapered when discontinued to minimize withdrawal effects, and the switching method depends on the specific SSRI being introduced, with most switches requiring either a gradual cross-taper or a taper-washout-start approach. 1

General Principles for SSRI Switching

The fundamental rule is that conservative switching strategies involve gradually tapering the first antidepressant followed by an adequate washout period before starting the new antidepressant, though this approach takes longer and includes periods without treatment. 2

Key Safety Considerations

• Never combine two SSRIs simultaneously without proper cross-tapering, as this significantly increases the risk of serotonin syndrome, a potentially life-threatening condition that can develop within 24-48 hours. 3, 4
• Serotonin syndrome presents with mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic instability (hypertension, tachycardia, diaphoresis). 3
• Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness. 3

Specific Switching Methods

Method 1: Direct Cross-Taper (Most Common for SSRI-to-SSRI Switches)

This method involves gradually reducing escitalopram while simultaneously introducing the new SSRI at a low starting dose, with careful monitoring during the overlap period. 2

Steps:

1. Reduce escitalopram by 5 mg (from 10 mg to 5 mg, or from 20 mg to 15 mg) 1
2. Simultaneously start the new SSRI at its lowest starting dose:
   • Sertraline 25 mg daily 1
   • Fluoxetine 10 mg daily 1
   • Citalopram 10 mg daily 1
   • Paroxetine 10 mg daily (though not recommended as first-line) 1
3. After 3-7 days, discontinue escitalopram completely while maintaining the new SSRI at starting dose 2
4. After another 3-7 days, increase the new SSRI to therapeutic dose if tolerated 1
5. Monitor closely for the first 24-48 hours after any dose change for signs of serotonin syndrome 3

Method 2: Taper-Washout-Start (Conservative Approach)

This method is safer but involves a treatment gap and should be used when switching to SSRIs with higher drug interaction potential or when patient has risk factors for serotonin syndrome. 2

Steps:

1. Taper escitalopram by 5 mg every 5-7 days until discontinued 1
2. Allow a washout period of 1-2 weeks (approximately 5 half-lives of escitalopram, which has a 27-32 hour half-life) 4, 2
3. Start the new SSRI at standard starting dose 1
4. Titrate to therapeutic dose based on response 1

This approach is particularly important when the patient is on other serotonergic medications (tramadol, trazodone, certain opioids, stimulants, or over-the-counter medications like dextromethorphan or St. John's Wort). 3

Monitoring Requirements

Close monitoring is essential, especially during the initial weeks of switching, as deliberate self-harm and suicide risk is more likely when SSRIs are started at higher doses or during dose changes. 1

• Contact (in-person or telephone) should occur within the first week after initiating the switch 1
• Monitor for adverse events including behavioral activation, switch to mania, and suicide-related events 1
• Assess for early response by week 2: patients with at least 20% symptom reduction are 6 times more likely to ultimately respond or remit 5
• If no meaningful benefit after 4 weeks at therapeutic dose with good adherence, consider switching to an antidepressant with a different pharmacodynamic profile 1

Common Pitfalls to Avoid

• Abrupt discontinuation or rapid dose reduction of escitalopram precipitates SSRI withdrawal syndrome 1
• Failing to account for over-the-counter medications and supplements (St. John's Wort, dextromethorphan, L-tryptophan) that increase serotonin syndrome risk 3
• Starting the new SSRI at too high a dose during cross-taper increases toxicity risk 1
• Inadequate washout time when using the conservative approach, particularly with longer half-life SSRIs 4, 2
• Not considering that only about 20% of patients remit with a second-step SSRI switch after initial SSRI failure, so realistic expectations should be set 5

Special Populations

• In older adults, escitalopram, sertraline, and citalopram are preferred agents; avoid paroxetine and fluoxetine due to higher adverse effect rates 1
• In adolescents, effective dosages are generally lower than adult guidelines, and only fluoxetine and escitalopram (ages 12+) are FDA-approved for this population 1
• Avoid SSRIs in patients with bipolar depression due to risk of mania 1

Duration of Second SSRI Trial

A 12-week trial duration at therapeutic dose appears necessary to capture as many second-step switch responders as possible, as half of responses and two-thirds of remissions occur after 6 weeks of treatment. 5