Vortioxetine

TRINTELLIX

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Pronunciation: vor-tye-OX-e-teen

Vortioxetine ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Vortioxetine ballicule

Vortioxetine TRINTELLIX mascot mnemonic cartoon — Visual mnemonic: Vortioxetine mascot
**“Trent’s Vortex”**
Trent Reznor (Nine Inch Nails)
“serotonergic vortex” of nausea
guitar pick-shaped tablets
“Fight the fog (machine) of depression” → cognitive benefits

What it isSerotonin reuptake inhibitor with additional receptor modulation; depression.

Why this oneEvidence for improving cognitive symptoms of depression, and less sexual dysfunction than an SSRI.

What limits itNausea is dose-related and the commonest reason for stopping. CYP2D6-dependent, and cost is a barrier.

Pearls

Less insomnia and weight gain than SSRIs.
Halve the dose with strong CYP2D6 inhibitors.
Cognitive advantage over other antidepressants remains unproven.

Vortioxetine molecular structure (skeletal formula) — Molecular structure: Vortioxetine

Vortioxetine prescription history

Animated chart of estimated U.S. prescriptions per year, Antidepressants (1957–2026). Vortioxetine enters in 2013 (estimated).

FDA-approved for

depression (2013)

Classes and tags

Clinical profile

Therapeutic safety burden1 / 4

Overdose danger1 / 4

Weight-gain liability1 / 4

Sedation liability1 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryC

Defining liabilityNausea, sexual effects and serotonin toxicity are the principal concerns.

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Suicidal thoughts and behaviors in pediatric and young adult patients; not approved for pediatric use

FDA dosing	Population	Start	Target	Max
Major depressive disorder (MDD)	adult	10 mg QD	20 mg QD	20 mg QD
MDD	CYP2D6 poor metabolizers	10 mg QD	10 mg QD	10 mg QD

Renal Undefined

Hepatic Undefined

5 mg/day may be considered for patients who do not tolerate higher doses

Instructions

Take with or without meals
Taper: reduce 15 or 20 mg/day to 10 mg/day for 1 week before full discontinuation
Allow 14 days after stopping an MAOI before starting; allow 21 days after stopping before starting an MAOI

Available strengths

tab 5, 10, 20 mg

Contraindications

MAOIs (concurrently or within 14 days) due to risk of serotonin syndrome

Cautions

Serotonin syndrome
Increased risk of bleeding (with NSAIDs, aspirin, warfarin, anticoagulants)
Activation of mania/hypomania — screen for bipolar disorder
Angle closure glaucoma
Hyponatremia/SIADH
Sexual dysfunction
Discontinuation syndrome

Adverse reactions

Nausea
Constipation
Vomiting

Pregnancy Limited data; third-trimester use may increase risk of PPHN and neonatal complications

Lactation No human milk data; weigh benefits against clinical need

Cost

Vortioxetine (TRINTELLIX)

What pharmacies pay · NADAC 9/30/26

Strength		#/mo	generic $/mo	brand $/mo	CostPlus
5 mg	tab	30 qd	—	$515.90	not offered
10 mg	tab	30 qd	—	$515.92	not offered
20 mg	tab	30 qd	—	$515.99	not offered

Generic entry2027 est.

Serotonin and MAOI

Provisional washout figures

SRI significance3 / 4

MAO-A inhibition0 / 4

Serotonin release0 / 4

Elevating mechanismSRI

Non-elevating action5-HT1A agonist; 5-HT1B partial agonist; 5-HT3/5-HT7 antagonist

Exposure dependenceTherapeutic exposure; severe toxicity requires meaningful MAO-A inhibition

Washout BEFORE an MAOI21 days

Evidence confidenceHigh

InterpretationClinically significant SRI despite multimodal receptor marketing. A second SRI generally represents therapeutic duplication/additive adverse effects, not the classic life-threatening interaction.

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Memory aids: interaction avatars

CYP2D6 substrate

CYP3A4 substrate

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Self-check

Which depression symptom domain has improvement evidence with vortioxetine?
Cognitive symptoms.
What is the commonest reason to stop vortioxetine?
Dose-related nausea.