Is it safe to discontinue fluoxetine (Selective Serotonin Reuptake Inhibitor) and start escitalopram (Lexapro) the next day?

Direct Switching from Fluoxetine to Escitalopram

No, you should not abruptly discontinue fluoxetine and start escitalopram the next day—fluoxetine's exceptionally long half-life (4-6 days for fluoxetine, 4-16 days for its active metabolite norfluoxetine) means it will remain in your system for weeks, making an immediate switch both unnecessary and potentially problematic due to overlapping serotonergic effects. 1

Why Fluoxetine is Unique Among SSRIs

Fluoxetine stands apart from other SSRIs due to its pharmacokinetic profile:

• Fluoxetine has the longest half-life of all SSRIs, with plasma concentrations decreasing gradually over weeks after discontinuation, which inherently minimizes discontinuation syndrome risk 1
• Abrupt discontinuation of fluoxetine is well-tolerated and safe, unlike shorter-acting SSRIs such as paroxetine, fluvoxamine, and sertraline that commonly cause withdrawal symptoms 2, 3
• Studies demonstrate that abrupt fluoxetine discontinuation produces no clinically significant discontinuation syndrome or symptom clusters, with only mild, self-limited dizziness occurring in a small percentage of patients 2

The Correct Approach to Switching

The safest strategy is to simply stop fluoxetine and wait 5-7 days before initiating escitalopram at 10 mg daily (the recommended starting dose per guidelines, not 5 mg). 4, 5

Rationale for the Waiting Period:

• The 5-7 day washout allows fluoxetine levels to decline substantially, reducing the risk of serotonin syndrome from overlapping serotonergic activity 5
• Serotonin syndrome is a potentially life-threatening condition characterized by mental status changes, autonomic instability, neuromuscular symptoms, and can occur when combining SSRIs 5
• The FDA explicitly contraindicates combining SSRIs with other serotonergic agents without careful monitoring due to serotonin syndrome risk 5

Escitalopram Dosing:

• Start escitalopram at 10 mg daily, not 5 mg—guidelines specify 10 mg as the appropriate starting dose for adolescents and adults 4
• After establishing tolerability, the dose can be increased by 5 mg increments to the effective dose of 10 mg (which is often the target dose) or up to a maximum of 20 mg 4
• Your proposed 5 mg starting dose for 3 days is unnecessarily cautious and not evidence-based

Important Safety Considerations

Monitoring Requirements:

• Close monitoring is essential during the initial weeks after any SSRI switch, particularly for clinical worsening, suicidality, and unusual behavioral changes 4
• The FDA black-box warning mandates observation for these symptoms, especially during the first few months and at dose changes 4
• Contact (in-person or telephone) should occur shortly after initiating escitalopram to assess adherence, adverse effects, and clinical status 4

Discontinuation Syndrome Awareness:

• While fluoxetine discontinuation is generally benign, escitalopram requires gradual tapering when eventually discontinued to avoid withdrawal symptoms including dysphoric mood, irritability, dizziness, sensory disturbances, anxiety, and headache 5
• A gradual dose reduction is recommended whenever possible rather than abrupt cessation of escitalopram 5

Common Pitfalls to Avoid

• Do not start escitalopram immediately after stopping fluoxetine—the washout period is critical for safety 5
• Do not start at 5 mg—this is below the evidence-based starting dose and delays achieving therapeutic levels 4
• Do not assume fluoxetine needs tapering—unlike other SSRIs, fluoxetine's long half-life provides a built-in taper, and abrupt discontinuation is safe 1, 2
• Do not combine with other serotonergic agents (triptans, tramadol, St. John's Wort, etc.) during the transition period without careful consideration of serotonin syndrome risk 5