Trintellix Tapering Guide
vortioxetine
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
Overview
Vortioxetine is a multimodal serotonergic antidepressant approved for major depressive disorder. Beyond SERT inhibition, it has direct activity at multiple serotonin receptors, which may contribute to pro-cognitive effects.
5mg, 10mg, 20mg
Tablets: 5mg, 10mg, 20mg
No assigned category; see FDA labeling (approved post-2015 PLLR rule)
Mechanism of Action
Multimodal serotonergic agent: inhibits the serotonin transporter (SERT) and also acts as a 5-HT3, 5-HT7, and 5-HT1D receptor antagonist, 5-HT1B partial agonist, and 5-HT1A agonist.
Taper Notes
Half-life of ~66 hours provides significant kinetic buffering. Limited published deprescribing data; extrapolate from general multimodal serotonergic principles. Tablets can be split for stepwise reductions.
Maudsley Deprescribing Guidance
Newer agent with limited published taper data. Apply general SSRI/multimodal hyperbolic principles: stepwise reductions of 5 mg, with extended hold periods if symptoms emerge. Tablet splitting is feasible.
Common Withdrawal Symptoms
Interactions & Safety
Drug Interactions
- MAOIs — contraindicated (serotonin syndrome risk)
- Strong CYP2D6 inhibitors (e.g., bupropion, fluoxetine, paroxetine) increase vortioxetine levels — reduce dose by 50%
- Strong CYP inducers (e.g., rifampin, carbamazepine) decrease vortioxetine levels — consider dose increase
Food Interactions
- No significant food effect on pharmacokinetics
- Avoid alcohol during treatment
Contraindications
- MAOIs within 21 days
- Known hypersensitivity to vortioxetine
Toxicity
Serotonin syndrome with serotonergic combinations. Generally well tolerated; nausea is the most common adverse effect.
Pharmacokinetics
ADME Profile
Well absorbed orally. Absolute bioavailability ~75%. Tmax 7–11 hours. Food does not affect pharmacokinetics.
~2600 L (~33 L/kg)
Extensively metabolized hepatically via CYP2D6 (primary), CYP3A4/5, CYP2C9, CYP2C19, CYP2A6, and CYP2C8. Major metabolite is pharmacologically inactive.
Renal (~59%) and fecal (~26%). Negligible unchanged drug in urine.
~98%
~33 L/hr (oral clearance)
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