Switching from Fluoxetine 40 mg to Vortioxetine
Due to fluoxetine's exceptionally long half-life (4-6 days) and its active metabolite norfluoxetine (4-16 days), you should taper fluoxetine gradually over 1-2 weeks, then implement a mandatory 5-7 day washout period before initiating vortioxetine at 10 mg daily. 1, 2
Critical Pharmacokinetic Considerations
Fluoxetine's Unique Elimination Profile
- Fluoxetine and norfluoxetine require approximately 4 weeks to reach steady-state and have elimination half-lives that necessitate extended washout periods when switching to other antidepressants 3, 4
- The long half-life means fluoxetine continues exerting pharmacologic effects for weeks after discontinuation, creating risk for drug interactions during transitions 5, 1
- Fluoxetine inhibits CYP2D6 and other cytochrome P450 enzymes, which can affect metabolism of subsequently introduced medications 6
Vortioxetine Pharmacokinetics
- Vortioxetine has a terminal half-life of approximately 66 hours and reaches steady-state within 2 weeks of dosing 2
- Vortioxetine is metabolized by CYP450 enzymes, making it susceptible to interactions with fluoxetine's persistent enzyme inhibition 2
Recommended Switching Protocol
Week 1-2: Fluoxetine Taper
- Reduce fluoxetine 40 mg to 20 mg daily for 7 days 1
- Then reduce to 20 mg every other day for 7 days 1
- Gradual tapering reduces risk and severity of discontinuation syndrome, which includes dizziness, fatigue, headaches, and sensory disturbances 7, 1
Week 3: Washout Period
- Implement a 5-7 day medication-free washout period 1, 8
- This washout is essential despite fluoxetine's long half-life to minimize risk of serotonergic drug interactions 1
- Monitor closely for withdrawal symptoms during this period 7
Week 4: Vortioxetine Initiation
- Start vortioxetine at 10 mg once daily 2
- After 1 week, may increase to 20 mg daily if tolerated and clinically indicated 2
- Vortioxetine dosing range is 5-20 mg daily, with dose adjustments made based on tolerability and response 2
Critical Safety Monitoring
Serotonin Syndrome Risk
- Monitor intensively for serotonin syndrome in the first 24-48 hours after initiating vortioxetine 7
- Watch for mental status changes, neuromuscular hyperactivity (tremor, rigidity, myoclonus), and autonomic hyperactivity (hyperthermia, tachycardia, diaphoresis) 7
- Risk is elevated due to residual fluoxetine and norfluoxetine in the system despite washout 1
Discontinuation Syndrome
- Fluoxetine has lower risk of discontinuation syndrome compared to other SSRIs due to its long half-life, but symptoms can still occur 7, 1
- If withdrawal symptoms emerge during taper, slow the tapering schedule further 7
Special Population Considerations
- CYP2D6 poor metabolizers require vortioxetine dose adjustment - consider reducing vortioxetine dose or extending washout period in known poor metabolizers 2
- Patients under age 24 require monitoring for suicidal thinking and behavior during the transition 6
Common Pitfalls to Avoid
- Never initiate vortioxetine immediately after stopping fluoxetine without a washout period - the residual fluoxetine and norfluoxetine create significant drug interaction risk 1, 8
- Do not abruptly discontinue fluoxetine 40 mg - this increases risk of withdrawal syndrome and potential relapse 1
- Avoid combining any serotonergic medications during the transition period 7
- Do not assume the washout period can be shortened - even after 2 weeks, significant fluoxetine levels remain due to the 4-16 day half-life of norfluoxetine 3, 4