What is the proper procedure for switching from Lexapro (escitalopram) 5 mg to Cymbalta (duloxetine)?

Switching from Lexapro 5 mg to Cymbalta

Use a cross-tapering approach: start duloxetine 30 mg once daily while maintaining escitalopram 5 mg for one week, then discontinue escitalopram and increase duloxetine to 60 mg once daily over the following 1-2 weeks. 1

Cross-Tapering Protocol

Week 1:

• Start duloxetine 30 mg once daily in the morning while continuing escitalopram 5 mg daily 1
• Take duloxetine with food to minimize nausea risk—this strategy significantly reduces gastrointestinal side effects, particularly at treatment initiation 2

Week 2:

• Discontinue escitalopram completely 1
• Continue duloxetine 30 mg once daily 1

Week 3 onward:

• Increase duloxetine to 60 mg once daily (the therapeutic target dose) 1, 2
• Starting at 30 mg for one week before increasing to 60 mg significantly reduces nausea risk compared to starting at 60 mg 1, 2

Critical Safety Monitoring During Transition

Serotonin Syndrome Surveillance:

• Monitor closely for mental status changes, neuromuscular hyperactivity (tremor, rigidity, myoclonus), and autonomic hyperactivity (diaphoresis, tachycardia, hyperthermia) during the overlap period 1
• Symptoms typically arise within 24-48 hours after combining serotonergic medications 1
• The conservative approach of starting duloxetine at 30 mg while tapering escitalopram mitigates this risk 1

Cardiovascular Monitoring:

• Check blood pressure and pulse at baseline and regularly during the transition 1
• Duloxetine increases mean systolic blood pressure by approximately 3.7 mmHg and pulse by approximately 3 bpm over 8 months of treatment 3
• Monitor for sustained hypertension, though incidence is low (approximately 1.5% of patients) 3

Discontinuation Syndrome Prevention

• Escitalopram has a relatively lower risk of discontinuation syndrome compared to shorter-acting SSRIs, but gradual tapering remains essential 1
• Watch for dizziness, fatigue, myalgias, headaches, nausea, insomnia, sensory disturbances, and anxiety during the escitalopram taper 1
• The one-week overlap period with continued escitalopram 5 mg provides therapeutic coverage while minimizing withdrawal symptoms 1

Common Side Effects to Anticipate

Early duloxetine side effects (first 1-2 weeks):

• Nausea (most common), dry mouth, diaphoresis, abdominal discomfort, dizziness, headache, tremor, insomnia, and somnolence 1
• These adverse events are typically mild, transient, and occur predominantly during the first week of duloxetine dosing at 60 mg 4
• Taking duloxetine with food substantially reduces nausea severity 2

Timing of adverse events:

• Duloxetine-associated adverse events (nausea, dry mouth) tend to emerge early in treatment, whereas escitalopram-associated events (diarrhea, weight increase) tend to emerge later 3
• Since you're discontinuing escitalopram early, expect primarily duloxetine-related side effects 3

Special Considerations for Low-Dose Escitalopram

• Since the patient is on only 5 mg escitalopram (a subtherapeutic dose), the risk of discontinuation syndrome is lower than with standard therapeutic doses (10-20 mg) 5
• However, maintain the gradual cross-taper to ensure therapeutic coverage and minimize any withdrawal symptoms 1

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 1
• Duloxetine 60 mg once daily is the therapeutic target for most patients with major depressive disorder 2, 3
• Rapid dose escalation (60 mg → 90 mg → 120 mg weekly) is safe and tolerable, with the majority of adverse events occurring at initial 60 mg dosing rather than during subsequent escalations 4

Modified Protocol for 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 1
• Duloxetine and escitalopram both require dose reduction in hepatic disease, and duloxetine requires adjustment in renal insufficiency 1

Common Pitfalls to Avoid

• Do not abruptly discontinue escitalopram—this significantly increases discontinuation syndrome risk even at low doses 6
• Do not start duloxetine at 60 mg without food—this maximizes nausea and early discontinuation risk 2
• Do not overlap both medications at full therapeutic doses—this increases serotonin syndrome risk 1
• Do not rush the cross-taper—allow at least one week at duloxetine 30 mg before escalating to 60 mg 1, 2