How do I switch from Lexapro (escitalopram) 5mg to Cymbalta (duloxetine)?

Switching from Lexapro 5mg to Cymbalta (Duloxetine)

Use a cross-taper approach: start duloxetine 30mg once daily while simultaneously reducing escitalopram from 5mg to 2.5mg daily for one week, then discontinue escitalopram and increase duloxetine to 60mg daily after the first week if tolerated. 1

Cross-Taper Protocol

Week 1:

• Start duloxetine 30mg once daily in the morning while reducing escitalopram from 5mg to 2.5mg daily 1
• The 30mg starting dose of duloxetine minimizes nausea, which is the most common side effect when initiating this medication 1
• This overlap period allows assessment of duloxetine tolerability before complete discontinuation of escitalopram 1

Week 2 and Beyond:

• Discontinue escitalopram completely 1
• Increase duloxetine to the target dose of 60mg once daily, which is the standard therapeutic dose for depression 2
• There is no evidence that doses higher than 60mg daily confer additional benefit, and higher doses are associated with more adverse effects 2

Critical Monitoring Requirements

Blood Pressure and Pulse:

• Monitor blood pressure and pulse regularly during the transition, as duloxetine has been associated with sustained increases in both parameters 3, 1
• SNRIs like duloxetine can cause sustained clinical hypertension 3

Common Side Effects to Anticipate:

• Nausea, vomiting, diarrhea, abdominal discomfort (most common reasons for discontinuation) 3
• Diaphoresis, dry mouth, dizziness, headache, tremor 3
• Insomnia or somnolence, decreased appetite, weight loss 3

Special Precautions

Discontinuation rates are higher with duloxetine compared to SSRIs as a class—67% increased risk of discontinuation due to adverse effects compared to SSRIs. 3

Hepatic Monitoring:

• Be alert for signs of hepatic failure: abdominal pain, hepatomegaly, elevated transaminases, or jaundice 3
• Discontinue duloxetine immediately and do not restart if jaundice or clinically significant liver dysfunction develops 3

Severe Skin Reactions:

• Discontinue duloxetine at the first appearance of blisters, peeling rash, mucosal erosions, or signs of hypersensitivity (erythema multiforme, Stevens-Johnson syndrome) 3

Contraindications and Drug Interactions

• Do not use duloxetine if the patient is taking MAOIs—at least 14 days must elapse after stopping an MAOI before starting duloxetine 2
• Avoid combining with other serotonergic medications due to risk of serotonin syndrome (tremor, diarrhea, delirium, neuromuscular rigidity, hyperthermia) 3
• Duloxetine may interact with drugs metabolized by CYP1A2 and CYP2D6 3

Adjustments for Special Populations

Elderly or Frail Patients:

• Consider a slower cross-taper with a lower initial duloxetine dose (20mg) 1

Renal Insufficiency:

• Avoid duloxetine in severe renal impairment (GFR <30 mL/min) 2
• Consider dosage adjustment for lesser degrees of renal insufficiency 1

Hepatic Impairment:

• Avoid duloxetine in patients with chronic liver disease or cirrhosis 2

Expected Outcomes

• Following an ineffective SSRI trial, switching to another antidepressant (including SNRIs like duloxetine) results in remission in approximately 21% of patients and response without remission in 9% 4
• About 58% will have no meaningful benefit from the switch 4
• Most responses and remissions occur after 6 weeks of treatment, with half of responses and two-thirds of remissions occurring after this timepoint 4
• A 12-week trial duration is necessary to capture as many responders as possible 4

Common Pitfalls to Avoid

• Do not abruptly discontinue escitalopram—even at the low 5mg dose, gradual tapering minimizes withdrawal symptoms (dizziness, headache, nausea, paresthesia, irritability) 2, 5
• Do not start duloxetine at 60mg—the 30mg starting dose for one week significantly reduces nausea risk 1
• Do not combine with NSAIDs, aspirin, or warfarin without caution—duloxetine increases bleeding risk 2
• Do not use heavy alcohol—concomitant use with duloxetine may be associated with severe liver injury 2