How do I switch from escitalopram (Lexapro) to fluoxetine (Prozac)?

Switching from Escitalopram to Fluoxetine

Stop escitalopram abruptly and start fluoxetine 20 mg daily the next day—escitalopram's shorter half-life requires no washout period when switching to fluoxetine, which has a uniquely long elimination half-life that provides built-in protection against discontinuation syndrome. 1

Switching Strategy

The reverse switch (fluoxetine to escitalopram) is well-documented with direct cessation due to fluoxetine's prolonged half-life 1, but when switching FROM escitalopram TO fluoxetine, the approach differs because escitalopram has a much shorter half-life and can cause discontinuation syndrome if stopped abruptly 2. However, starting fluoxetine immediately provides overlapping serotonergic coverage that prevents withdrawal symptoms while the escitalopram clears 3, 4.

Practical Implementation

• Stop escitalopram completely on day 1 5
• Start fluoxetine 20 mg daily on day 2 (standard starting dose for adults) 3, 4
• No tapering of escitalopram is required because fluoxetine's long half-life (4-6 days for fluoxetine, 4-16 days for its active metabolite norfluoxetine) creates a natural taper effect that prevents discontinuation symptoms 3, 4
• This is a conservative direct switch strategy that avoids the risks of cross-tapering two SSRIs simultaneously 5

Dosing Considerations

• Fluoxetine 20 mg daily is the standard starting and therapeutic dose for most adults 3, 4
• Fluoxetine can be increased to 40-80 mg daily if needed for treatment response, but start at 20 mg to assess tolerability 4
• Escitalopram and fluoxetine have roughly equivalent efficacy at standard doses (escitalopram 10-20 mg ≈ fluoxetine 20-40 mg) 2

Critical Monitoring in First 24-48 Hours

Watch closely for serotonin syndrome symptoms during the first 24-48 hours after starting fluoxetine, though risk is relatively low with this single-agent switch 2, 1:

• Mental status changes: confusion, agitation, anxiety 2
• Neuromuscular hyperactivity: tremors, clonus, hyperreflexia, muscle rigidity 2
• Autonomic hyperactivity: hypertension, tachycardia, tachypnea, diaphoresis, fever 2

Ongoing Monitoring (Weeks 1-4)

• Assess for behavioral activation, increased anxiety, or agitation—common early SSRI side effects that may differ between escitalopram and fluoxetine 1
• Monitor for suicidal ideation and behavior, particularly in adolescents and young adults during the first few months 1
• Evaluate for treatment response using standardized symptom scales at 2-4 week intervals 1
• Watch for GI symptoms (nausea, diarrhea), headache, insomnia, or sexual dysfunction—fluoxetine's side effect profile may differ from escitalopram 2

Important Safety Considerations

Drug Interactions

• Fluoxetine has MORE CYP450 interactions than escitalopram, particularly affecting CYP2D6 and CYP2C19 substrates 2
• Escitalopram has minimal CYP450 enzyme effects, while fluoxetine significantly inhibits CYP2D6 (affecting drugs like tamoxifen, codeine, metoprolol) 2, 1
• Avoid combining with MAOIs—requires 5-week washout after stopping fluoxetine before starting an MAOI due to fluoxetine's long half-life 2
• Exercise caution with other serotonergic drugs including tramadol, triptans, other antidepressants, dextromethorphan, and St. John's wort 2, 1

Common Pitfalls to Avoid

• Do NOT cross-taper (overlapping both medications at full doses for extended periods)—this unnecessarily increases serotonin syndrome risk 5
• Do NOT use a washout period between stopping escitalopram and starting fluoxetine—this creates a treatment gap that risks symptom relapse 5
• Do NOT taper escitalopram slowly before the switch unless the patient has a history of severe discontinuation symptoms with prior SSRI changes—the immediate fluoxetine start provides adequate coverage 5, 4

Advantages of This Switch

Fluoxetine is uniquely suited as a "destination" SSRI when discontinuing other antidepressants because its long half-life minimizes discontinuation syndrome if future tapering is needed 3, 4. This makes it an excellent choice for patients who have experienced withdrawal symptoms with escitalopram dose reductions or who may need to discontinue antidepressants in the future 6, 4.