Vortioxetine

Summary

Vortioxetine (CHEMBL2104993) is an approved small-molecule antidepressant (ATC N06AX26) targeting HTR5A, HTR6, and HTR7; indicated across 7 conditions including major depressive disorder and depressive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06AX26
• Targets: 7 (HTR5A, HTR6, HTR7…)
• Indications: 7 conditions
• Clinical trials: 88
• Chemistry: 298.4 Da · C18H22N2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2104993
Name	Vortioxetine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	9966051
ChEBI	CHEBI:76016
ATC	N06AX26
Molecular formula	C18H22N2S
Molecular weight	298.4
InChIKey	YQNWZWMKLDQSAC-UHFFFAOYSA-N

SMILES: CC1=CC(=C(C=C1)SC2=CC=CC=C2N3CCNCC3)C

IUPAC name: 1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine

ChEBI definition: An N-arylpiperazine in which the aryl group is specified as 2-[(2,4-dimethylphenyl)sulfanyl]phenyl. Used (as its hydrobromide salt) for treatment of major depressive disorder.

Pharmacological roles (ChEBI): antidepressant, anxiolytic drug, serotonergic agonist, serotonergic antagonist.

Also known as: Brintellix, LU AA21004, LU-AA21004, LUAA21004, Vortioxetina, Vortioxetine, VORTIOXETINE, Vortioxetine hydrobromideÊ, Vortioxetine hydrobromideÂ, Lu AA21004, VORTIOXETINE HYDROBROMIDE

Parent form; salt/anhydrous children: CHEMBL2107387, CHEMBL2204360, CHEMBL3260563, CHEMBL5314578

Patent coverage: 886 distinct patent families (2,164 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 2,125 (98%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
HTR5A	5-HT5A receptor	Antagonist	6.66	0%	P47898
HTR6	5-HT6 receptor	Antagonist	6.48	0.2%	P50406
HTR7	5-HT7 receptor	Antagonist	6.35	0.8%	P34969
HTR1A	5-HT1A receptor	Partial agonist	7.82	0%	P08908
HTR1B	5-HT1B receptor	Partial agonist	7.48	0.2%	P28222
	5-HT3AB	Partial agonist	8.43
HTR1D	5-HT1D receptor	Antagonist	5.4	0%	P28221
SLC6A4	SERT	Inhibition	8.8	0.7%	P31645

Broader ChEMBL bioactivity targets: 7 (assay-derived). Sample: 5-hydroxytryptamine receptor 3A, 5-hydroxytryptamine receptor 1A, Prostaglandin G/H synthase 1, Sodium-dependent serotonin transporter, Prostaglandin G/H synthase 2, Sodium-dependent serotonin transporter, 5-hydroxytryptamine receptor 7.

Bioactivity

ChEMBL activities: 19 potent at pChembl ≥ 5 of 19 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SLC6A4	8.8	Ki	1.6	nM	CHEMBL_ACT_24961687
P31652	8.54	IC50	2.9	nM	CHEMBL_ACT_18467404
P31652	8.54	IC50	2.9	nM	CHEMBL_ACT_18698907
P31652	8.54	IC50	2.9	nM	CHEMBL_ACT_19283887
P31652	8.54	IC50	2.9	nM	CHEMBL_ACT_19289430
PTGS2	8.51	IC50	3.11	nM	CHEMBL_ACT_24972132
HTR3A	8.43	Ki	3.7	nM	CHEMBL_ACT_24961686
PTGS1	8.29	IC50	5.19	nM	CHEMBL_ACT_24972128
SLC6A4	8.27	IC50	5.4	nM	CHEMBL_ACT_25447767
HTR1A	8.02	Ki	9.5	nM	CHEMBL_ACT_18467408
HTR1A	8.02	Ki	9.5	nM	CHEMBL_ACT_18698938
HTR1A	8.02	Ki	9.5	nM	CHEMBL_ACT_19283856
HTR1A	8.02	Ki	9.5	nM	CHEMBL_ACT_19289424
HTR1A	7.82	Ki	15	nM	CHEMBL_ACT_24961685
HTR7	7.72	Ki	19	nM	CHEMBL_ACT_24961691
HTR7	7.58	Ki	26	nM	CHEMBL_ACT_18467412
HTR7	7.58	Ki	26	nM	CHEMBL_ACT_18698969
HTR7	7.58	Ki	26	nM	CHEMBL_ACT_19283869
HTR7	7.58	Ki	26	nM	CHEMBL_ACT_19289427

Target pathways

Aggregated over 7 target gene(s): HTR5A, HTR6, HTR7, HTR1A, HTR1B, HTR1D, SLC6A4.

Top Reactome pathways

15 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	6	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
Signaling by GPCR	6	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
Class A/1 (Rhodopsin-like receptors)	6	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
Amine ligand-binding receptors	6	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
Serotonin receptors	6	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
GPCR ligand binding	6	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
GPCR downstream signalling	5	HTR1B, HTR1D, HTR5A, HTR6, HTR7
G alpha (i) signalling events	3	HTR1B, HTR1D, HTR5A
G alpha (s) signalling events	2	HTR6, HTR7
Neurotransmitter clearance	1	SLC6A4
Transmission across Chemical Synapses	1	SLC6A4
Neuronal System	1	SLC6A4
Serotonin clearance from the synaptic cleft	1	SLC6A4
SLC-mediated transport of neurotransmitters	1	SLC6A4
RHOBTB3 ATPase cycle	1	HTR7

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	6
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	6
chemical synaptic transmission	6
signal transduction	6
adenylate cyclase-inhibiting serotonin receptor signaling pathway	4
G protein-coupled serotonin receptor signaling pathway	4
vasoconstriction	4
adenylate cyclase-activating G protein-coupled receptor signaling pathway	3
regulation of behavior	3
response to estradiol	2
adenylate cyclase-activating serotonin receptor signaling pathway	2
smooth muscle contraction	2
circadian rhythm	2
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	2
hippocampus development	1

Indications & clinical

Indications

7 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
major depressive disorder	3	MONDO:0002009	MONDO:0002009
depressive disorder	3	MONDO:0002050	MONDO:0002050
generalized anxiety disorder	3	MONDO:0001942	EFO:1001892
attention deficit-hyperactivity disorder	2	MONDO:0007743	EFO:0003888
eating disorder	2	MONDO:0005451	EFO:0005203
bipolar disorder	2	MONDO:0004985	MONDO:0004985
liver disorder	1	MONDO:0005154	EFO:0001421

Clinical trials

Total trials: 88.

Phase distribution

Phase	Trials
PHASE3	31
PHASE4	27
PHASE2	10
Not specified	7
PHASE1	6
PHASE2/PHASE3	4
EARLY_PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06805266	PHASE4	NOT_YET_RECRUITING	Vortioxetine for Depressive Symptoms and Freezing of Gait in Parkinson Disease
NCT07266545	PHASE4	RECRUITING	RNA Editing as a Biomarker of Antidepressant Response in Unipolar and Bipolar Depression (EDIT-ANDRE)
NCT02234362	PHASE4	COMPLETED	Vortioxetine for Menopausal Depression
NCT02294305	PHASE4	UNKNOWN	Vortioxetine Versus Placebo in Major Depressive Disorder Comorbid With Social Anxiety Disorder
NCT02332954	PHASE4	COMPLETED	Assessment in Work Productivity and the Relationship With Cognitive Symptoms in Patients With MDD Taking Vortioxetine
NCT02357797	PHASE4	UNKNOWN	Adjunctive Vortioxetine in Schizophrenia
NCT02371980	PHASE4	COMPLETED	Vortioxetine, 5, 10, and 20 mg, Relapse Prevention Study in Adults With Major Depressive Disorder (MDD)
NCT02395510	PHASE4	COMPLETED	A 10-Week, Open-Label, Flexible Dose Adaptive Study Evaluating the Efficacy of Vortioxetine in Subjects With Panic Disorder
NCT02637466	PHASE4	WITHDRAWN	Vortioxetine for MDD, Cognition, and Systemic Inflammatory Biomarkers
NCT02637895	PHASE4	COMPLETED	Vortioxetine for Posttraumatic Stress Disorder
NCT02749721	PHASE4	COMPLETED	The Relationship Among Changes in Brain Network Activation in Adult Outpatients With Major Depressive Disorder
NCT02932904	PHASE4	COMPLETED	Effect of Vortioxetine, Paroxetine, and Placebo on Sexual Functioning in Healthy Volunteers
NCT02969876	PHASE4	TERMINATED	Pattern Separation, Brain Derived Neurotrophic Factors, and Mechanisms of Vortioxetine
NCT02972632	PHASE4	COMPLETED	Goal Achievement After a Change to Vortioxetine in Adults With Major Depressive Disorder
NCT03187093	PHASE4	UNKNOWN	Cognitive Dysfunction in MDD Patients
NCT03272711	PHASE4	COMPLETED	Remediation of Age-related Cognitive Decline: Vortioxetine and Cognitive Training
NCT03580967	PHASE4	WITHDRAWN	Vortioxetine Monotherapy for Major Depressive Disorder in Type 2 Diabetes
NCT03779789	PHASE4	COMPLETED	Vortioxetine in the Elderly vs. Selective Serotonin Reuptake Inhibitors (SSRIs): a Pragmatic Assessment
NCT03830827	PHASE4	UNKNOWN	MBRP + Vortioxetine VS MBRP on Preventing Relapse in Chronic MA Users
NCT03835715	PHASE4	COMPLETED	Study With Vortioxetine on Emotional Functioning in Patients With Depression
NCT03978286	PHASE4	COMPLETED	Vortioxetine vs Sertraline in Mexicans
NCT04220996	PHASE4	COMPLETED	Vortioxetine in Patients With Depression Coexisting With General Anxiety Disorder (GAD)
NCT04288895	PHASE4	COMPLETED	Open-label, Flexible-dose Study of Vortioxetine in Patients With Depression in India
NCT04294654	PHASE4	COMPLETED	Vortioxetine in Patients With Depression and Early Dementia
NCT04301492	PHASE4	UNKNOWN	Tolerability, Safety and Efficacy of Vortioxetine
NCT04448431	PHASE4	COMPLETED	Comparison of Vortioxetine and Desvenlafaxine in Adult Patients Suffering From Depression
NCT05481957	PHASE4	COMPLETED	Vortioxetine Adjunctive Treatment in Bipolar Depression
NCT07204314	PHASE3	RECRUITING	A Study of Vortioxetine in Japanese Pediatric Patients With Major Depressive Disorder
NCT00672620	PHASE3	COMPLETED	Efficacy and Safety of Vortioxetine (Lu AA21004) in the Treatment of Patients With Major Depressive Disorder
NCT00672958	PHASE3	COMPLETED	Efficacy and Safety of Vortioxetine (Lu AA21004) in Treating Adults With Major Depressive Disorder
NCT00707980	PHASE3	COMPLETED	Safety and Tolerability of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
NCT00730691	PHASE3	COMPLETED	Efficacy of Vortioxetine (Lu AA21004) in Treating Generalized Anxiety Disorder
NCT00731120	PHASE3	COMPLETED	Study of Efficacy and Safety of Vortioxetine (Lu AA21004) in Treating Generalized Anxiety Disorder
NCT00734071	PHASE3	COMPLETED	An Efficacy and Safety Study of Vortioxetine (Lu AA21004) in Treating Generalized Anxiety Disorder
NCT00735709	PHASE3	COMPLETED	Efficacy Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
NCT00744627	PHASE3	COMPLETED	Efficacy and Safety of Vortioxetine (Lu AA21004) for Treatment of Generalized Anxiety Disorder in Adults.
NCT00788034	PHASE3	COMPLETED	Relapse-prevention Study With Lu AA21004 (Vortioxetine) in Patients With Generalized Anxiety Disorder
NCT01152996	PHASE3	COMPLETED	Safety and Tolerability of Vortioxetine (LuAA21004) - Open Label Extension Study
NCT01153009	PHASE3	COMPLETED	Safety and Efficacy of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
NCT01163266	PHASE3	COMPLETED	Efficacy and Safety Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (3) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for vortioxetine and CYP2D6	CPIC	CYP2D6	yes	yes
Annotation of CPIC Guideline for desvenlafaxine, duloxetine, fluoxetin	CPIC	HTR2A
Annotation of CPIC Guideline for citalopram, desvenlafaxine, duloxetin	CPIC	SLC6A4

PharmGKB also curates 1 clinical and 3 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

675 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
BREXPIPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7, SLC6A4
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7, SLC6A4
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7, SLC6A4
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7, SLC6A4
CARIPRAZINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7, SLC6A4
KETANSERIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7, SLC6A4
NEFAZODONE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7, SLC6A4
RISPERIDONE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7, SLC6A4
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR5A, HTR6, HTR7, SLC6A4
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR5A, HTR6, HTR7, SLC6A4
TEGASEROD	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1D, HTR5A, HTR6, HTR7, SLC6A4
CINACALCET	ChEMBL	Phase 4 (approved)	HTR1A, HTR1D, HTR5A, HTR6, HTR7, SLC6A4
VILAZODONE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR6, HTR7, SLC6A4
SEROTONIN	ChEMBL	Phase 3	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
MEBUFOTENIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
NIGULDIPINE	ChEMBL	Phase 2	HTR1A, HTR1B, HTR5A, HTR6, HTR7, SLC6A4
PENFLURIDOL	ChEMBL	Phase 2	HTR1A, HTR1D, HTR5A, HTR6, HTR7, SLC6A4
PSILOCIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
RITANSERIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR5A, HTR6, HTR7, SLC6A4
AMOXAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7, SLC6A4
CHLORPROMAZINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7, SLC6A4
Cyproheptadine	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7, SLC6A4
DOXEPIN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7, SLC6A4
HALOPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7, SLC6A4
LOXAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7, SLC6A4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7, SLC6A4
AZELASTINE	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR6, HTR7, SLC6A4
ERGOTAMINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6
MIANSERIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1D, HTR6, HTR7, SLC6A4
PROMAZINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7, SLC6A4
SALMETEROL	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR7, SLC6A4
SUMATRIPTAN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR7
FANANSERIN	ChEMBL	Phase 2	HTR1A, HTR5A, HTR6, HTR7, SLC6A4
LYSERGIDE	ChEMBL	Phase 2	HTR1A, HTR1D, HTR5A, HTR6, HTR7
SPIPERONE	ChEMBL	Phase 2	HTR1A, HTR5A, HTR6, HTR7, SLC6A4
SPIRAMIDE	ChEMBL	Phase 2	HTR1A, HTR1D, HTR6, HTR7, SLC6A4
PAROXETINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, SLC6A4
Pramipexole	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR5A, HTR7
SORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7
CARVEDILOL	ChEMBL	Phase 4 (approved)	HTR1A, HTR6, HTR7, SLC6A4
DIBENZEPIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR6, HTR7, SLC6A4
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR6, HTR7, SLC6A4
FROVATRIPTAN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR7
OXYMETAZOLINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR6
SERTINDOLE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR6, SLC6A4
SILODOSIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR7
SUNITINIB	ChEMBL	Phase 4 (approved)	HTR1A, HTR5A, HTR6, SLC6A4
THIORIDAZINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR6, HTR7, SLC6A4
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	HTR1A, HTR6, HTR7, SLC6A4
LATREPIRDINE	ChEMBL	Phase 3	HTR1D, HTR5A, HTR6, HTR7
YOHIMBINE	ChEMBL	Phase 3	HTR1A, HTR1B, HTR1D, HTR6
CHLOROPHENYLPIPERAZINE	ChEMBL	Phase 2	HTR1A, HTR6, HTR7, SLC6A4
GSK163090	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR7
METERGOLINE	ChEMBL	Phase 2	HTR1A, HTR6, HTR7, SLC6A4
METITEPINE	ChEMBL	Phase 2	HTR1A, HTR5A, HTR6, HTR7
QUIPAZINE	ChEMBL	Phase 2	HTR1A, HTR6, HTR7, SLC6A4
Pyrazinamide	PubChem	Approved	HTR1A, HTR6, HTR7, SLC6A4
Tiotropium Bromide Monohydrate	PubChem	Approved	HTR5A, HTR6, HTR7, SLC6A4
DIPHENHYDRAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR5A, HTR6, SLC6A4
Fluoxetine	ChEMBL + PubChem	Phase 4 (approved)	HTR5A, HTR6, SLC6A4