What is the recommended cross‑taper schedule from Lexapro (escitalopram) to Cymbalta (duloxetine)?

Cross-Taper from Lexapro to Cymbalta

Start duloxetine 30 mg once daily while simultaneously reducing escitalopram from your current dose to 20 mg daily, then after one week increase duloxetine to 60 mg daily while further tapering escitalopram to 10 mg daily for one week, and finally discontinue escitalopram while maintaining duloxetine 60 mg daily. 1, 2

Recommended Cross-Taper Schedule

Week 1:

• Start duloxetine 30 mg once daily
• Reduce escitalopram to 20 mg daily (if currently on higher dose)
• This overlap minimizes withdrawal symptoms while establishing therapeutic coverage 1, 2

Week 2:

• Increase duloxetine to 60 mg once daily
• Reduce escitalopram to 10 mg daily
• Starting duloxetine at 30 mg for one week significantly reduces treatment-emergent nausea compared to starting directly at 60 mg 1, 2

Week 3:

• Continue duloxetine 60 mg once daily
• Discontinue escitalopram completely
• The target therapeutic dose for most indications is 60 mg once daily 1

Evidence Supporting This Approach

The cross-tapering method is superior to abrupt switching because it maintains therapeutic coverage while minimizing discontinuation syndrome from escitalopram. 1, 2 Research demonstrates that immediate switching from SSRIs to duloxetine 60 mg daily without tapering is well-tolerated, with actually lower discontinuation rates due to adverse events (6.3%) compared to patients initiating duloxetine without prior antidepressant exposure (16.1%). 3 However, the gradual cross-taper remains the preferred guideline-recommended approach because it allows time to assess duloxetine tolerability before complete escitalopram discontinuation. 1

Critical Safety Monitoring During Transition

Serotonin syndrome surveillance:

• Monitor closely during the overlap period (weeks 1-2) for mental status changes, neuromuscular hyperactivity (tremor, rigidity), and autonomic hyperactivity (tachycardia, diaphoresis, hyperthermia) 2
• Symptoms typically arise within 24-48 hours after combining serotonergic medications 2
• The conservative low-dose duloxetine start (30 mg) mitigates this risk 2

Cardiovascular monitoring:

• Check blood pressure and pulse at baseline, week 1, week 2, and week 4 2
• Duloxetine can cause sustained elevations in both blood pressure and heart rate 2
• This is particularly important because escitalopram does not typically raise blood pressure, so patients may develop new hypertension during the switch 2

Common Side Effects to Anticipate

Most frequent with duloxetine initiation:

• Nausea (most common—occurs in >10% of patients) 1, 2
• Dry mouth, diaphoresis, headache 2
• Dizziness, insomnia or somnolence 2
• Constipation, diarrhea, abdominal discomfort 2

Key tolerability advantage of this schedule: Starting at 30 mg for one week before increasing to 60 mg significantly reduces nausea risk compared to starting directly at 60 mg. 1, 2 In the first week, patients switched from SSRIs to duloxetine report significantly lower rates of headache and fatigue compared to patients initiating duloxetine without prior antidepressant treatment. 3

Escitalopram discontinuation symptoms to watch for:

• Dizziness, fatigue, myalgias, headaches 2
• Nausea, insomnia, sensory disturbances ("brain zaps"), anxiety 2
• Escitalopram has relatively lower risk of discontinuation syndrome compared to shorter-acting SSRIs like paroxetine, but gradual tapering remains essential 2

Special Population Modifications

Elderly or frail patients:

• Use a slower schedule: start duloxetine 20 mg daily (instead of 30 mg) 1, 2
• Extend each phase by an additional week 2
• Monitor more closely for cognitive impairment, falls, and orthostatic hypotension 4

Renal insufficiency:

• Duloxetine dosage requires adjustment in renal impairment 1, 2
• Use caution and consider slower titration 1

Hepatic disease:

• Both duloxetine and escitalopram require dose reduction in hepatic impairment 2
• Duloxetine is contraindicated in severe hepatic disease 2

When to Escalate Duloxetine Beyond 60 mg

If clinical response is inadequate at duloxetine 60 mg daily after 4-8 weeks, the dose can be increased to 90 mg daily or 120 mg daily (given as 60 mg twice daily). 2 Research shows that approximately one-third of patients stabilize at each of the three studied doses (60,90, and 120 mg daily), with no difference in dose distribution between patients switching from SSRIs versus those initiating duloxetine. 3

Critical Pitfalls to Avoid

Do not abruptly stop escitalopram: Even though immediate switching to duloxetine 60 mg is tolerated in research settings, 3 the gradual cross-taper is preferred in clinical practice to minimize discontinuation syndrome risk. 1, 2

Do not start duloxetine at 60 mg in most patients: Starting at 30 mg for one week reduces nausea and improves tolerability. 1, 2 The exception is research protocols that demonstrate immediate switching is feasible, 3 but this is not the guideline-recommended approach. 1, 2

Do not combine with other serotonergic medications: Avoid tramadol, triptans, linezolid, or other serotonergic agents during the overlap period due to serotonin syndrome risk. 2

Do not ignore cardiovascular parameters: Duloxetine can cause clinically significant hypertension and tachycardia that escitalopram does not typically cause. 2 Failure to monitor may allow unrecognized cardiovascular changes. 2

Monitor for hepatotoxicity: Discontinue duloxetine immediately if jaundice, abdominal pain, hepatomegaly, or elevated transaminases develop. 2 This is a rare but serious adverse effect. 4

Comparative Efficacy Context

Head-to-head trials show mixed results. One study found escitalopram resulted in significantly greater improvement on depression rating scales with better tolerability (87% completion rate versus 69% for duloxetine, with 2% versus 13% discontinuation due to adverse events). 5 However, another non-inferiority study demonstrated duloxetine is at least as fast as escitalopram in onset of antidepressant action, with both drugs showing significant improvement over placebo. 6 A Japanese acceptability trial found escitalopram superior to duloxetine as a second-line treatment (4.9% versus 19.2% discontinuation rate). 7 Despite these findings, both medications are effective antidepressants, and the choice often depends on comorbid conditions—duloxetine offers advantages for patients with concurrent chronic pain conditions. 4