What is the proper procedure for switching from Lexapro (escitalopram) to Cymbalta (duloxetine)?

Switching from Lexapro (Escitalopram) to Cymbalta (Duloxetine)

Use a cross-tapering approach: start duloxetine 30 mg once daily while simultaneously reducing escitalopram from your current dose to 20 mg daily, then continue the gradual transition over 1-2 weeks to minimize withdrawal symptoms and maintain therapeutic coverage. 1

Cross-Tapering Schedule

Week 1:

• Start duloxetine 30 mg once daily while reducing escitalopram to 20 mg daily (if currently on higher doses) 1
• The 30 mg starting dose of duloxetine reduces the risk of nausea, which is the most common side effect when initiating this medication 1

Week 2:

• Increase duloxetine to 60 mg once daily (the standard therapeutic dose for depression) 1
• Reduce escitalopram to 10 mg daily 1

Week 3:

• Continue duloxetine 60 mg once daily 1
• Discontinue escitalopram completely 1

This gradual cross-taper allows time to assess duloxetine tolerability before completely discontinuing escitalopram, which is critical for maintaining therapeutic efficacy throughout the transition. 1

Critical Safety Monitoring

Serotonin Syndrome Risk:

• Monitor closely for serotonin syndrome symptoms during the overlap period: mental status changes (confusion, agitation, anxiety), neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis, vomiting, diarrhea) 2, 3
• Symptoms typically arise within 24-48 hours after combining serotonergic medications 2
• While cross-tapering two non-MAOI serotonergic drugs requires caution, the conservative approach of starting duloxetine at low dose (30 mg) and increasing slowly mitigates this risk 2

Cardiovascular Monitoring:

• Monitor blood pressure and pulse regularly during the transition, as duloxetine has been associated with increases in these parameters 1, 3
• This is particularly important as escitalopram does not typically cause these effects 2

Common Side Effects to Anticipate:

• Duloxetine commonly causes nausea, dry mouth, diaphoresis, abdominal discomfort, dizziness, headache, tremor, insomnia, and somnolence 1
• Starting at 30 mg for one week before increasing to 60 mg significantly reduces nausea risk 1

Special Population Considerations

Elderly or Frail Patients:

• Use a slower cross-taper schedule with a lower initial duloxetine dose (20 mg instead of 30 mg) 1
• Extend each phase by an additional week to allow for better tolerance 1

Renal or Hepatic Impairment:

• Duloxetine dosage requires adjustment in renal insufficiency 1
• Both duloxetine and escitalopram require dose reduction in hepatic disease 2

Discontinuation Syndrome Prevention

Escitalopram has a relatively lower risk of discontinuation syndrome compared to shorter-acting SSRIs like paroxetine, but gradual tapering remains essential. 2

• The cross-tapering approach inherently prevents abrupt discontinuation of escitalopram 4
• Discontinuation syndrome symptoms include dizziness, fatigue, myalgias, headaches, nausea, insomnia, sensory disturbances, and anxiety 2
• The gradual reduction over 2-3 weeks while introducing duloxetine provides therapeutic coverage and minimizes withdrawal risk 4

Dose Escalation Beyond 60 mg (If Needed)

• If clinical response is inadequate at duloxetine 60 mg daily after 4-8 weeks, the dose can be increased to 120 mg daily (given as 60 mg twice daily) 1, 5
• Dose escalation from 60 mg to 90 mg to 120 mg has been shown to be safe and tolerable, with most adverse events occurring at initial dosing rather than during escalation 5

Key Clinical Pitfall to Avoid

Never abruptly stop escitalopram and immediately start duloxetine at full dose—this increases both withdrawal syndrome risk and duloxetine side effects, leading to poor tolerability and treatment discontinuation. 4, 6 The conservative cross-taper with low-dose duloxetine initiation is essential for successful switching 1.