Switching from Prozac Extended Release to Lexapro
Stop Prozac extended release abruptly without tapering and wait 5-7 days before starting Lexapro at standard dosing (10 mg daily). 1, 2
Rationale for Direct Switch Strategy
Fluoxetine's exceptionally long half-life (4-6 days for the parent compound, 4-16 days for its active metabolite norfluoxetine) provides a built-in taper effect that makes abrupt discontinuation safe and appropriate. 1 This pharmacokinetic property distinguishes fluoxetine from all other SSRIs and eliminates the need for gradual dose reduction. 3, 4
Step-by-Step Switching Protocol
Week 1: Discontinuation Phase
- Stop Prozac extended release immediately without any tapering schedule 1
- Wait 5-7 days minimum before initiating Lexapro to minimize drug interaction risk and serotonin syndrome 2
- Monitor the patient during this washout period for any emerging symptoms 2
Week 2: Initiation Phase
- Start escitalopram (Lexapro) at 10 mg daily after the washout period 1
- Do not cross-taper or overlap these medications due to increased serotonin syndrome risk 2
Weeks 2-6: Monitoring Phase
- Assess treatment response at 4-6 weeks after initiating Lexapro at therapeutic dose 2
- Monitor for improvement in depressive symptoms 2
- Evaluate tolerability and side effects 1
Critical Safety Considerations
Why Cross-Tapering is Contraindicated
Never overlap or cross-taper fluoxetine with escitalopram. 2 The combination increases serotonin syndrome risk and creates unpredictable escitalopram levels due to fluoxetine's potent CYP2D6 inhibition and prolonged presence in the system. 2
Managing Withdrawal Symptoms During Washout
While fluoxetine discontinuation syndrome is uncommon due to its extended half-life, if intolerable withdrawal symptoms emerge during the 5-7 day washout period: 1, 3
- Temporarily reinstate fluoxetine at a lower dose (e.g., 10-20 mg) 2
- Taper more gradually over 10-14 days before attempting the switch again 2
- Contact the patient within 1-2 weeks to assess for withdrawal symptoms 2
Serotonin Syndrome Monitoring
Watch for the triad of serotonin syndrome during and after the switch: 2
- Mental status changes (agitation, confusion)
- Neuromuscular hyperactivity (tremor, hyperreflexia, clonus)
- Autonomic instability (tachycardia, hyperthermia, diaphoresis)
Common Pitfalls to Avoid
Do not mistake withdrawal symptoms for depression relapse. 3 Discontinuation symptoms are typically somatic (dizziness, nausea, flu-like symptoms) rather than purely psychological, though anxiety and irritability can occur. 3
Do not start Lexapro too early. The 5-7 day washout is essential despite fluoxetine's self-tapering effect, as active metabolites remain in the system and can interact with the new SSRI. 2
Do not assume all SSRIs switch the same way. This direct-stop strategy is unique to fluoxetine; switching from shorter half-life SSRIs like paroxetine or sertraline to Lexapro would require gradual tapering. 3, 5
Dose Adjustments for Special Populations
For elderly patients or those with hepatic impairment, consider starting Lexapro at 5 mg daily (50% of standard adult dose) after the washout period, as older adults are at significantly greater risk of adverse drug reactions. 1