How do I switch from Prozac (fluoxetine) to Trintellix (vortioxetine)?

Switching from Prozac (Fluoxetine) to Trintellix (Vortioxetine)

Due to fluoxetine's exceptionally long half-life (4-6 days for the parent compound, 4-16 days for its active metabolite), you should discontinue fluoxetine and wait at least 5-7 days before initiating vortioxetine to minimize risk of serotonin syndrome and drug interactions. 1, 2

Switching Strategy

Step 1: Discontinue Fluoxetine

• Abruptly stop fluoxetine without tapering, as its long half-life provides a built-in taper effect 1, 3
• Fluoxetine's extended half-life (very long compared to other SSRIs) means withdrawal symptoms are less likely to manifest 1
• The active metabolite norfluoxetine remains in the system for weeks, providing gradual dose reduction naturally 1

Step 2: Washout Period

• Wait 5-7 days minimum before starting vortioxetine 1, 2, 3
• This washout period is critical because:
  • Prevents serotonin syndrome from combining serotonergic agents 1, 2
  • Allows clearance of fluoxetine and its metabolites to reduce drug-drug interactions 1
  • Fluoxetine inhibits CYP2D6, which can affect vortioxetine metabolism 1, 2

Step 3: Initiate Vortioxetine

• Start vortioxetine at 10 mg once daily 2
• May increase to 20 mg/day as tolerated after one week if needed for efficacy 2
• May decrease to 5 mg/day if 10 mg is not tolerated 2
• The majority of patients in clinical trials received 10-20 mg doses 2

Monitoring During the Switch

Watch for Withdrawal Symptoms (Days 1-14)

• Monitor for SSRI discontinuation syndrome, though less common with fluoxetine than shorter-acting SSRIs like paroxetine 1, 4, 5
• Key symptoms to assess: dizziness, headache, nausea, flu-like symptoms, anxiety, irritability, insomnia 4, 5
• Contact patients within 1-2 weeks of discontinuation to assess for withdrawal symptoms 1

Monitor for Serotonin Syndrome (First 24-48 hours after starting vortioxetine)

• Critical symptoms: mental status changes (confusion, agitation), neuromuscular hyperactivity (tremor, rigidity, hyperreflexia), autonomic instability (tachycardia, hypertension, diaphoresis) 1
• Risk is elevated when combining serotonergic agents, though the washout period minimizes this 1, 2

Assess Treatment Response

• Evaluate response at 4-6 weeks after initiating vortioxetine at therapeutic dose 1
• Monitor for improvement in depressive symptoms and cognitive function (vortioxetine has unique procognitive properties) 2, 6
• If inadequate response after 6-8 weeks at maximum tolerated dose, consider alternative strategies 1

Important Caveats

Why Not Cross-Taper?

• Cross-tapering fluoxetine with vortioxetine is NOT recommended due to:
  • Increased risk of serotonin syndrome from combining serotonergic agents 1, 2
  • Fluoxetine's CYP2D6 inhibition can increase vortioxetine levels unpredictably 1, 2
  • The long half-life makes cross-tapering unnecessary and potentially dangerous 3

Alternative for Severe Withdrawal

• If withdrawal symptoms are intolerable during the washout period (rare with fluoxetine), temporarily reinstate fluoxetine at a lower dose then taper more gradually over 10-14 days before attempting the switch again 1, 4, 5
• Consider switching to fluoxetine from other antidepressants to facilitate discontinuation, but this is not needed when switching FROM fluoxetine 7

Contraindications

• Do not use vortioxetine with MAOIs or within 14 days of stopping an MAOI 2
• Allow 21 days after stopping vortioxetine before starting an MAOI 2
• Avoid combining with other serotonergic drugs (triptans, tramadol, St. John's wort) without careful monitoring 1, 2

Expected Adverse Effects with Vortioxetine

• Most common: nausea (typically mild-moderate and transient), headache 2, 6
• Vortioxetine has lower rates of sexual dysfunction compared to SSRIs like fluoxetine, which may be an advantage for patients experiencing this side effect 2, 6
• Generally well-tolerated with favorable adverse effect profile 6