Biomarker & Intervention Discovery

Major Depressive Disorder

This page lists 14 druggable gene targets, 39 approved or trial-tested drug candidates and 15 recent clinical trials for Major Depressive Disorder, with each agent ranked by the strength of its evidence (clinical, mechanistic or correlative). Candidates include existing drugs that could be repurposed. Sources are linked so you can check every claim.

Plain-language summary → New Treatments for Major Depressive Disorder (2026)

US DALYs3.50MWHO GHE 2021 · all ages
Global DALYs56.53MWHO GHE 2021 · worldwide
NIH funding$694MFY2025 · RCDC estimate
Funding levelUnderfunded
Spontaneous remissionRelapse in 19-45% within 1 year of antidepressant discontinuation after remission; relapse risk ratio (off-medication…
Best-intervention remission55-80% remain relapse-free at 1 year after well-managed discontinuation; psychotherapy (CBT) achieves comparable…
Gap sizeModerate; narrows substantially over time for maintenance medication question
Primary barrierpractice
Full remission profile →
Research Tracker Chronic Disease Interventions Major Depressive Disorder Biomarker Atlas →

Remission & chronicity

Spontaneous remission
Relapse in 19-45% within 1 year of antidepressant discontinuation after remission; relapse risk ratio (off-medication vs on) falls from 3.69x at 2 months to 1.34x at 5 years
Best-intervention remission
55-80% remain relapse-free at 1 year after well-managed discontinuation; psychotherapy (CBT) achieves comparable remission with better durability; psilocybin-assisted therapy showing 29-71% response at 3 months in treatment-resistant cases
Gap size
Moderate; narrows substantially over time for maintenance medication question
Primary barrier
practice
Guidelines push long maintenance durations partly because short-term relapse risk is high, but long-term maintenance evidence is weaker than commonly assumed; psychotherapy significantly underutilized relative to medication

Biomarker Targets & Therapeutic Agents

Gene targets queried against DGIdb, Open Targets, ChEMBL, PubMed, and Europe PMC. Agents ranked: Clinical > Mechanistic > Correlative.

BDNF 123CRH 9DRD2 427FKBP5 194GRIN2B 238HTR1A 82HTR2A 122IL6 173MAOA 39MAOB 218NTRK2 206SLC6A2 269SLC6A3 176SLC6A4 104

BDNF

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
TRAMADOL ? unclear Mechanistic DGIdb
FLUTICASONE ↑ activates Mechanistic DGIdb
IONOMYCIN ? unclear Mechanistic DGIdb
MONOAMINE OXIDASE INHIBITOR ? unclear Mechanistic DGIdb
FREUND'S ADJUVANT ? unclear Mechanistic DGIdb
LITHIUM ? unclear Mechanistic DGIdb
ZINC SULFATE ANHYDROUS ? unclear Mechanistic DGIdb
CAPSAICIN ? unclear Mechanistic DGIdb
PROPRANOLOL HYDROCHLORIDE ? unclear Mechanistic DGIdb
MARIJUANA ? unclear Mechanistic DGIdb
NORTRIPTYLINE ? unclear Mechanistic DGIdb
BORTEZOMIB ? unclear Mechanistic DGIdb
GLUCAGON (RDNA) ? unclear Mechanistic DGIdb
COLCHICINE ? unclear Mechanistic DGIdb
DOXEPIN HYDROCHLORIDE ? unclear Mechanistic DGIdb
DRONABINOL ? unclear Mechanistic DGIdb
TANAPROGET ↑ activates Mechanistic DGIdb
CYCLOOXYGENASE INHIBITOR ? unclear Mechanistic DGIdb
VERTEPORFIN ? unclear Mechanistic DGIdb
ANTIOXIDANT ? unclear Mechanistic DGIdb
DITIOCARB ? unclear Mechanistic DGIdb
APR19 ↓ inhibits Mechanistic DGIdb
DOXORUBICIN HYDROCHLORIDE ? unclear Mechanistic DGIdb
OPIATE ? unclear Mechanistic DGIdb
OXIDOPAMINE ? unclear Mechanistic DGIdb
TETRADECANOYLPHORBOL ACETATE ? unclear Mechanistic DGIdb
INSULIN, REGULAR, HUMAN ? unclear Mechanistic DGIdb
PROPYLTHIOURACIL ? unclear Mechanistic DGIdb
TROGLITAZONE ? unclear Mechanistic DGIdb
TYROSINE HYDROXYLASE INHIBITOR ? unclear Mechanistic DGIdb
ALTEPLASE ? unclear Mechanistic DGIdb
MEDICATION ? unclear Mechanistic DGIdb
HALOPERIDOL DECANOATE ? unclear Mechanistic DGIdb
ASOPRISNIL ↓ inhibits Mechanistic DGIdb
ANALGESIC AGENT ? unclear Mechanistic DGIdb
TCDD ? unclear Mechanistic DGIdb
THERAPEUTIC GONADOTROPIN ? unclear Mechanistic DGIdb
METHADONE HYDROCHLORIDE ? unclear Mechanistic DGIdb
RECOMBINANT TRANSFORMING GROWTH FACTOR ? unclear Mechanistic DGIdb
ONAPRISTONE ↓ inhibits Mechanistic DGIdb

Showing top 40 of 123 agents ranked by evidence tier.

CRH

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
ROSIGLITAZONE ? unclear Mechanistic DGIdb
ACIVICIN ↓ inhibits Mechanistic DGIdb
MEDICATION ? unclear Mechanistic DGIdb
GGSTOP ↓ inhibits Mechanistic DGIdb
ANTIDEPRESSANT AGENT ? unclear Mechanistic DGIdb
IRX-2 ? unclear Mechanistic DGIdb
ANTISERUM ? unclear Mechanistic DGIdb
NALOXONE HYDROCHLORIDE ? unclear Mechanistic DGIdb
CHEMBL5286255 ↓ inhibits Mechanistic 0.7 nM (Ki) ChEMBL

DRD2

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
ASENAPINE ? unclear Mechanistic DGIdb
MEPHENTERMINE ? unclear Mechanistic DGIdb
HALOPERIDOL LACTATE ↓ inhibits Mechanistic DGIdb
BREXPIPRAZOLE ↑ activates Mechanistic DGIdb
ANALGESIC AGENT ? unclear Mechanistic DGIdb
AXITINIB ↓ inhibits Mechanistic DGIdb
RG-1530 ↓ inhibits Mechanistic DGIdb
LOXAPINE SUCCINATE ↓ inhibits Mechanistic DGIdb
QUETIAPINE FUMARATE ↓ inhibits Mechanistic DGIdb
PROCHLORPERAZINE ↓ inhibits Mechanistic DGIdb
APOMORPHINE ↑ activates Mechanistic DGIdb
PRAMIPEXOLE ? unclear Mechanistic DGIdb
THIETHYLPERAZINE MALEATE ↓ inhibits Mechanistic DGIdb
IBCASERTIB ↓ inhibits Mechanistic DGIdb
FAMITINIB ↓ inhibits Mechanistic DGIdb
SOXATALTINIB ↓ inhibits Mechanistic DGIdb
SUMANIROLE ↑ activates Mechanistic 9.0 nM (Ki) DGIdb
DOCARPAMINE ? unclear Mechanistic DGIdb
PALIPERIDONE ↓ inhibits Mechanistic DGIdb
PRIDOPIDINE ~ modulates Mechanistic DGIdb
OLANZAPINE ↓ inhibits Mechanistic 20.0 nM (Ki) DGIdb
PEGDINETANIB ↓ inhibits Mechanistic DGIdb
RISPERIDONE ↓ inhibits Mechanistic DGIdb
PERGOLIDE MESYLATE ↑ activates Mechanistic DGIdb
LISURIDE ? unclear Mechanistic 0.5 nM (Ki) DGIdb
ZICRONAPINE ? unclear Mechanistic DGIdb
CLEBOPRIDE ↓ inhibits Mechanistic DGIdb
LAZERTINIB ↓ inhibits Mechanistic DGIdb
REMOXIPRIDE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
CABERGOLINE ↑ activates Mechanistic DGIdb
JNJ-37822681 ↓ inhibits Mechanistic DGIdb
ERGOT ALKALOIDS ? unclear Mechanistic DGIdb
(-)-STEPHOLIDINE ? unclear Mechanistic DGIdb
SARIZOTAN HYDROCHLORIDE ↑ activates Mechanistic DGIdb
5-OH-DPAT ? unclear Mechanistic DGIdb
LITHIUM ? unclear Mechanistic DGIdb
DIHYDROERGOTOXINE ? unclear Mechanistic DGIdb
REMOXIPRIDE ↓ inhibits Mechanistic DGIdb
BROMPERIDOL ↓ inhibits Mechanistic DGIdb
PHENTOLAMINE ? unclear Mechanistic DGIdb

Showing top 40 of 427 agents ranked by evidence tier.

FKBP5

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
CITALOPRAM ? unclear Mechanistic DGIdb
CLOMIPRAMINE ? unclear Mechanistic DGIdb
ZAK INHIBITOR 6P ↓ inhibits Mechanistic DGIdb
GEMCITABINE ? unclear Mechanistic DGIdb
KC-130 ↓ inhibits Mechanistic DGIdb
THERAPEUTIC CORTICOSTEROID ? unclear Mechanistic DGIdb
NEFAZODONE ? unclear Mechanistic DGIdb
COMPOUND 15B [PMID: 16539403] ↓ inhibits Mechanistic DGIdb
LIOTHYRONINE ? unclear Mechanistic DGIdb
LITHIUM ? unclear Mechanistic DGIdb
BUPROPION HYDROCHLORIDE ? unclear Mechanistic DGIdb
CLOZAPINE ? unclear Mechanistic DGIdb
CHEMBL321022 ↓ inhibits Mechanistic 6300.0 nM (IC50) ChEMBL
CHEMBL2058222 ↓ inhibits Mechanistic 62800.0 nM (IC50) ChEMBL
CHEMBL2058223 ↓ inhibits Mechanistic 30700.0 nM (IC50) ChEMBL
CHEMBL2058224 ↓ inhibits Mechanistic 11600.0 nM (IC50) ChEMBL
CHEMBL2058226 ↓ inhibits Mechanistic 67100.0 nM (IC50) ChEMBL
CHEMBL2058227 ↓ inhibits Mechanistic 28500.0 nM (IC50) ChEMBL
CHEMBL2058228 ↓ inhibits Mechanistic 47200.0 nM (IC50) ChEMBL
CHEMBL2058229 ↓ inhibits Mechanistic 45400.0 nM (IC50) ChEMBL
CHEMBL2058232 ↓ inhibits Mechanistic 54050.0 nM (IC50) ChEMBL
CHEMBL2058233 ↓ inhibits Mechanistic 15780.0 nM (IC50) ChEMBL
CHEMBL2058234 ↓ inhibits Mechanistic 22600.0 nM (IC50) ChEMBL
CHEMBL2058237 ↓ inhibits Mechanistic 29600.0 nM (IC50) ChEMBL
CHEMBL2058238 ↓ inhibits Mechanistic 88200.0 nM (IC50) ChEMBL
CHEMBL2058494 ↓ inhibits Mechanistic 6200.0 nM (IC50) ChEMBL
CHEMBL2058495 ↓ inhibits Mechanistic 16400.0 nM (IC50) ChEMBL
CHEMBL2058496 ↓ inhibits Mechanistic 16100.0 nM (IC50) ChEMBL
CHEMBL2058498 ↓ inhibits Mechanistic 27200.0 nM (IC50) ChEMBL
CHEMBL2058500 ↓ inhibits Mechanistic 18400.0 nM (IC50) ChEMBL
CHEMBL2058787 ↓ inhibits Mechanistic 14700.0 nM (IC50) ChEMBL
CHEMBL2058791 ↓ inhibits Mechanistic 66270.0 nM (IC50) ChEMBL
CHEMBL2058794 ↓ inhibits Mechanistic 456.0 nM (IC50) ChEMBL
CHEMBL2058796 ↓ inhibits Mechanistic 2030.0 nM (IC50) ChEMBL
CHEMBL2058797 ↓ inhibits Mechanistic 12300.0 nM (IC50) ChEMBL
CHEMBL2058800 ↓ inhibits Mechanistic 9690.0 nM (IC50) ChEMBL
CHEMBL2058801 ↓ inhibits Mechanistic 51500.0 nM (IC50) ChEMBL
CHEMBL2058802 ↓ inhibits Mechanistic 32730.0 nM (IC50) ChEMBL
CHEMBL2059024 ↓ inhibits Mechanistic 4150.0 nM (IC50) ChEMBL
CHEMBL2059025 ↓ inhibits Mechanistic 15340.0 nM (IC50) ChEMBL

Showing top 40 of 194 agents ranked by evidence tier.

GRIN2B

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
DIMIRACETAM ? unclear Mechanistic DGIdb
KETAMINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
PERZINFOTEL ↓ inhibits Mechanistic DGIdb
[3H]CGP39653 ↓ inhibits Mechanistic DGIdb
PHENCYCLIDINE ↓ inhibits Mechanistic DGIdb
DEXANABINOL ? unclear Mechanistic DGIdb
RAPASTINEL ↑ activates Mechanistic DGIdb
DELUCEMINE ↓ inhibits Mechanistic DGIdb
AMANTADINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
RISLENEMDAZ ↓ inhibits Mechanistic DGIdb
ORPHENADRINE CITRATE ↓ inhibits Mechanistic DGIdb
ELIPRODIL ? unclear Mechanistic 13.0 nM (Ki) DGIdb
INDANTADOL ? unclear Mechanistic DGIdb
SEVOFLURANE ? unclear Mechanistic DGIdb
SAGE-718 ~ modulates Mechanistic DGIdb
L689560 ↓ inhibits Mechanistic DGIdb
ONFASPRODIL ~ modulates Mechanistic DGIdb
HOMOQUINOLINIC ACID ↑ activates Mechanistic DGIdb
NEBOGLAMINE ~ modulates Mechanistic DGIdb
DIZOCILPINE ↓ inhibits Mechanistic DGIdb
LY233053 ↓ inhibits Mechanistic DGIdb
GLYCINE ↑ activates Mechanistic DGIdb
ESKETAMINE ~ modulates Mechanistic DGIdb
[3H]CGP61594 ↓ inhibits Mechanistic DGIdb
ORPHENADRINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
[3H]MDL105519 ↓ inhibits Mechanistic DGIdb
RADIPRODIL ? unclear Mechanistic DGIdb
NBQX ? unclear Mechanistic DGIdb
SEMAPIMOD ↓ inhibits Mechanistic DGIdb
SELFOTEL ↓ inhibits Mechanistic DGIdb
SERINE, D- ↑ activates Mechanistic DGIdb
COMPOUND 18C [PMID: 25901531] ↓ inhibits Mechanistic DGIdb
AZD8108 ↓ inhibits Mechanistic DGIdb
[3H]L689560 ↓ inhibits Mechanistic DGIdb
TRAXOPRODIL ↓ inhibits Mechanistic 74.0 nM (IC50) DGIdb
HALOPERIDOL DECANOATE ? unclear Mechanistic DGIdb
N1-DANSYL-SPERMINE ↓ inhibits Mechanistic DGIdb
[3H]D-ASPARTIC ACID ↑ activates Mechanistic DGIdb
NERAMEXANE ? unclear Mechanistic DGIdb
NVP-AAM077 ↓ inhibits Mechanistic DGIdb

Showing top 40 of 238 agents ranked by evidence tier.

HTR1A

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
SERTRALINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
QUETIAPINE FUMARATE ? unclear Mechanistic DGIdb
FLIBANSERIN ? unclear Mechanistic DGIdb
SARIZOTAN HYDROCHLORIDE ↑ activates Mechanistic DGIdb
LISURIDE ? unclear Mechanistic DGIdb
CLOZAPINE ? unclear Mechanistic DGIdb
BIFEPRUNOX ↑ activates Mechanistic DGIdb
DU 125530 ↓ inhibits Mechanistic DGIdb
ILOPERIDONE ? unclear Mechanistic DGIdb
XALIPRODEN ↑ activates Mechanistic DGIdb
BUSPIRONE HYDROCHLORIDE ↑ activates Mechanistic DGIdb
ENSACULIN HYDROCHLORIDE ? unclear Mechanistic DGIdb
VORTIOXETINE HYDROBROMIDE ↑ activates Mechanistic DGIdb
NORTRIPTYLINE ? unclear Mechanistic DGIdb
ELTOPRAZINE ? unclear Mechanistic DGIdb
ARIPIPRAZOLE LAUROXIL ↑ activates Mechanistic DGIdb
METHYSERGIDE ? unclear Mechanistic DGIdb
TRAZODONE ? unclear Mechanistic DGIdb
PIROMELATINE ? unclear Mechanistic DGIdb
ULOTARONT ↑ activates Mechanistic DGIdb
MN-305 ? unclear Mechanistic DGIdb
CLOMIPRAMINE ? unclear Mechanistic DGIdb
OXYMETAZOLINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
BUSPIRONE ? unclear Mechanistic DGIdb
MILNACIPRAN ? unclear Mechanistic DGIdb
MONOAMINE OXIDASE INHIBITOR ? unclear Mechanistic DGIdb
TRIMIPRAMINE ? unclear Mechanistic DGIdb
MIRTAZAPINE ? unclear Mechanistic DGIdb
GEPIRONE ↑ activates Mechanistic DGIdb
OPC-14523 ? unclear Mechanistic DGIdb
BREXPIPRAZOLE ↑ activates Mechanistic DGIdb
ALVERINE ↓ inhibits Mechanistic DGIdb
NALUZOTAN ↑ activates Mechanistic DGIdb
PARDOPRUNOX ↑ activates Mechanistic DGIdb
MAZAPERTINE SUCCINATE ? unclear Mechanistic DGIdb
METHAMPHETAMINE ? unclear Mechanistic DGIdb
DOXEPIN HYDROCHLORIDE ? unclear Mechanistic DGIdb
AMISULPRIDE ↓ inhibits Mechanistic DGIdb
DEXFENFLURAMINE HYDROCHLORIDE ↑ activates Mechanistic DGIdb
NARATRIPTAN ? unclear Mechanistic DGIdb

Showing top 40 of 82 agents ranked by evidence tier.

HTR2A

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
RISPERIDONE ↓ inhibits Mechanistic DGIdb
THIORIDAZINE ↓ inhibits Mechanistic DGIdb
BREXPIPRAZOLE ↓ inhibits Mechanistic DGIdb
CHLORPROMAZINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
PRUVANSERIN ↓ inhibits Mechanistic DGIdb
OCAPERIDONE ? unclear Mechanistic DGIdb
IFERANSERIN ↓ inhibits Mechanistic DGIdb
SARPOGRELATE ↓ inhibits Mechanistic DGIdb
KETANSERIN ? unclear Mechanistic DGIdb
LOXAPINE ↓ inhibits Mechanistic DGIdb
CHLORPROTHIXENE ↓ inhibits Mechanistic DGIdb
CHLORPROMAZINE ↓ inhibits Mechanistic DGIdb
VABICASERIN HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
ARIPIPRAZOLE LAUROXIL ↓ inhibits Mechanistic DGIdb
HALOPERIDOL DECANOATE ↓ inhibits Mechanistic DGIdb
METHYSERGIDE ? unclear Mechanistic DGIdb
TRELANSERIN ↓ inhibits Mechanistic DGIdb
MINAPRINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
ZIPRASIDONE ↓ inhibits Mechanistic DGIdb
QUETIAPINE FUMARATE ↓ inhibits Mechanistic DGIdb
MIANSERIN ? unclear Mechanistic DGIdb
DOXEPIN HYDROCHLORIDE ? unclear Mechanistic DGIdb
LOXAPINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
VOLINANSERIN ↓ inhibits Mechanistic DGIdb
ANIRACETAM ? unclear Mechanistic DGIdb
LUMATEPERONE ↓ inhibits Mechanistic DGIdb
TEDATIOXETINE ↓ inhibits Mechanistic DGIdb
ONDANSETRON HYDROCHLORIDE ? unclear Mechanistic DGIdb
DROPERIDOL ↓ inhibits Mechanistic DGIdb
TERGURIDE ? unclear Mechanistic DGIdb
PALIPERIDONE ↓ inhibits Mechanistic DGIdb
NELOTANSERIN ↓ inhibits Mechanistic DGIdb
CLOTHIAPINE ↓ inhibits Mechanistic DGIdb
THIOTHIXENE ↓ inhibits Mechanistic DGIdb
ZOTEPINE ? unclear Mechanistic DGIdb
LOXAPINE SUCCINATE ↓ inhibits Mechanistic DGIdb
MINAPRINE ↓ inhibits Mechanistic DGIdb
USTEKINUMAB ? unclear Mechanistic DGIdb
HALOPERIDOL LACTATE ↓ inhibits Mechanistic DGIdb
ERGOT ALKALOIDS ? unclear Mechanistic DGIdb

Showing top 40 of 122 agents ranked by evidence tier.

IL6

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
CISPLATIN ? unclear Mechanistic DGIdb
ZILTIVEKIMAB ~ modulates Mechanistic DGIdb
CHINESE HERBS ? unclear Mechanistic DGIdb
PF-04236921 ↓ inhibits Mechanistic DGIdb
MRA 003 US ↓ inhibits Mechanistic DGIdb
SIGNAL TRANSDUCTION INHIBITOR ? unclear Mechanistic DGIdb
BINETRAKIN ? unclear Mechanistic DGIdb
IBUDILAST ? unclear Mechanistic DGIdb
INSULIN, REGULAR, HUMAN ? unclear Mechanistic DGIdb
SILTUXIMAB ↓ inhibits Mechanistic DGIdb
METRONIDAZOLE ? unclear Mechanistic DGIdb
CLAZAKIZUMAB ↓ inhibits Mechanistic DGIdb
GALLIUM NITRATE ? unclear Mechanistic DGIdb
INTERFERON ALFA-2B ? unclear Mechanistic DGIdb
DULOXETINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
MEDI-5117 ↓ inhibits Mechanistic DGIdb
GEMFIBROZIL ? unclear Mechanistic DGIdb
BIAFINE CREAM ? unclear Mechanistic DGIdb
ETANERCEPT ? unclear Mechanistic DGIdb
ELSILIMOMAB ↓ inhibits Mechanistic DGIdb
SAQUINAVIR ? unclear Mechanistic DGIdb
INFLIXIMAB ? unclear Mechanistic DGIdb
LINEZOLID ? unclear Mechanistic DGIdb
IFOSFAMIDE ? unclear Mechanistic DGIdb
OLOKIZUMAB ↓ inhibits Mechanistic DGIdb
HMG-COA REDUCTASE INHIBITOR ? unclear Mechanistic DGIdb
MIDOSTAURIN ? unclear Mechanistic DGIdb
SELENIUM ? unclear Mechanistic DGIdb
SIRUKUMAB ↓ inhibits Mechanistic DGIdb
PEGINTERFERON ALFA-2B ? unclear Mechanistic DGIdb
ECHINACEA PREPARATION ? unclear Mechanistic DGIdb
ENZYME INHIBITOR ? unclear Mechanistic DGIdb
FENOFIBRATE MICRONIZED ? unclear Mechanistic DGIdb
VITAMIN K ? unclear Mechanistic DGIdb
PEGINTERFERON ALFA-2A ? unclear Mechanistic DGIdb
RIBAVIRIN ? unclear Mechanistic DGIdb
VITAMIN A PALMITATE ? unclear Mechanistic DGIdb
ARSENIC TRIOXIDE ? unclear Mechanistic DGIdb
DIHYDROSPHINGOSINE ? unclear Mechanistic DGIdb
LEVOFLOXACIN ANHYDROUS ? unclear Mechanistic DGIdb

Showing top 40 of 173 agents ranked by evidence tier.

MAOA

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
CLORGILINE ? unclear Mechanistic DGIdb
METHAMPHETAMINE ? unclear Mechanistic DGIdb
ISOCARBOXAZID ↓ inhibits Mechanistic DGIdb
CHEMBL:CHEMBL1927670 ? unclear Mechanistic DGIdb
MEBANAZINE ↓ inhibits Mechanistic DGIdb
NIALAMIDE ↓ inhibits Mechanistic DGIdb
HARMINE ? unclear Mechanistic DGIdb
MINAPRINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
NAPHTHOQUINONE ? unclear Mechanistic DGIdb
MOCLOBEMIDE ↓ inhibits Mechanistic DGIdb
CHEMBL:CHEMBL1927684 ? unclear Mechanistic DGIdb
NICOTINE POLACRILEX ? unclear Mechanistic DGIdb
TRANYLCYPROMINE ↓ inhibits Mechanistic DGIdb
INDANTADOL ? unclear Mechanistic DGIdb
CHEMBL:CHEMBL1813518 ? unclear Mechanistic DGIdb
CHEMBL:CHEMBL602466 ? unclear Mechanistic DGIdb
ANTIDEPRESSANT AGENT ? unclear Mechanistic DGIdb
PHENELZINE ? unclear Mechanistic DGIdb
PIPERINE ? unclear Mechanistic DGIdb
PARGYLINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
CX157 ? unclear Mechanistic DGIdb
IPRONIAZID ↓ inhibits Mechanistic DGIdb
PHENOXYPROPAZINE ↓ inhibits Mechanistic DGIdb
SELEGILINE ? unclear Mechanistic DGIdb
PSORALEN ? unclear Mechanistic DGIdb
TRYPTAMINE ? unclear Mechanistic DGIdb
CHEMBL:CHEMBL1642672 ? unclear Mechanistic DGIdb
PHENELZINE SULFATE ↓ inhibits Mechanistic DGIdb
1-PHENETHYLPIPERIDINE ? unclear Mechanistic DGIdb
TOLOXATONE ↓ inhibits Mechanistic DGIdb
CHEMBL:CHEMBL602260 ? unclear Mechanistic DGIdb
MINAPRINE ↓ inhibits Mechanistic DGIdb
CHEMBL:CHEMBL2088301 ? unclear Mechanistic DGIdb
PROXIBARBAL ↑ activates Mechanistic DGIdb
LADOSTIGIL ? unclear Mechanistic DGIdb
VITAMIN K3 ? unclear Mechanistic DGIdb
CHEMBL:CHEMBL2088303 ? unclear Mechanistic DGIdb
PARGYLINE ? unclear Mechanistic Open Targets
TRANYLCYPROMINE SULFATE ? unclear Mechanistic Open Targets

MAOB

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
SAFINAMIDE ↓ inhibits Mechanistic 450.0 nM (Ki) DGIdb
LEVODOPA ? unclear Mechanistic DGIdb
CHEMBL:CHEMBL1927670 ? unclear Mechanistic DGIdb
MOCLOBEMIDE ↓ inhibits Mechanistic 100000.0 nM (Ki) DGIdb
CHEMBL:CHEMBL1927684 ? unclear Mechanistic DGIdb
SELEGILINE ↓ inhibits Mechanistic 970.0 nM (Ki) DGIdb
BIFEMELANE ↓ inhibits Mechanistic DGIdb
MEBANAZINE ↓ inhibits Mechanistic DGIdb
MELATONIN ? unclear Mechanistic DGIdb
PARGYLINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
CHEMBL:CHEMBL602260 ? unclear Mechanistic DGIdb
ISOCARBOXAZID ↓ inhibits Mechanistic DGIdb
SEROTONIN ? unclear Mechanistic DGIdb
[18F]FLUORORASAGILINE ? unclear Mechanistic DGIdb
RASAGILINE ↓ inhibits Mechanistic 700.0 nM (Ki) DGIdb
CHEMBL:CHEMBL1642672 ? unclear Mechanistic DGIdb
PHENOXYPROPAZINE ↓ inhibits Mechanistic DGIdb
LAZABEMIDE ↓ inhibits Mechanistic 84.0 nM (Ki) DGIdb
NIALAMIDE ↓ inhibits Mechanistic DGIdb
CHEMBL:CHEMBL1813518 ? unclear Mechanistic DGIdb
SAFINAMIDE MESYLATE ↓ inhibits Mechanistic DGIdb
COBALAMIN ? unclear Mechanistic DGIdb
PHENELZINE ↓ inhibits Mechanistic DGIdb
RASAGILINE TARTRATE ↓ inhibits Mechanistic DGIdb
RALFINAMIDE ↓ inhibits Mechanistic DGIdb
SELEGILINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
VITAMIN K3 ? unclear Mechanistic DGIdb
CHEMBL:CHEMBL2088303 ? unclear Mechanistic DGIdb
TRANYLCYPROMINE ↓ inhibits Mechanistic DGIdb
PARGYLINE ? unclear Mechanistic 1800.0 nM (Ki) DGIdb
ANTIDEPRESSANT AGENT ? unclear Mechanistic DGIdb
MOFEGILINE ? unclear Mechanistic DGIdb
INDANTADOL ? unclear Mechanistic DGIdb
NAPHTHOQUINONE ? unclear Mechanistic DGIdb
METHAMPHETAMINE ? unclear Mechanistic DGIdb
HALOPERIDOL DECANOATE ? unclear Mechanistic DGIdb
PHENELZINE SULFATE ↓ inhibits Mechanistic DGIdb
IPRONIAZID ↓ inhibits Mechanistic 7540.0 nM (IC50) DGIdb
LINEZOLID ↓ inhibits Mechanistic DGIdb
CHEMBL:CHEMBL602466 ? unclear Mechanistic DGIdb

Showing top 40 of 218 agents ranked by evidence tier.

NTRK2

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
CYCLOSPORINE ? unclear Mechanistic DGIdb
CLOZAPINE ? unclear Mechanistic DGIdb
DIETHYLDITHIOCARBAMATE ? unclear Mechanistic DGIdb
CENEGERMIN ↑ activates Mechanistic DGIdb
LINIFANIB ? unclear Mechanistic 1100.0 nM (Kd) DGIdb
DORAMAPIMOD ? unclear Mechanistic 570.0 nM (Kd) DGIdb
AZD-6918 ↓ inhibits Mechanistic DGIdb
ENTRECTINIB ↓ inhibits Mechanistic 2.512 nM (Ki) DGIdb
TAMATINIB ? unclear Mechanistic DGIdb
PD-0166285 ? unclear Mechanistic 1584.89 nM (Ki) DGIdb
SORAFENIB ? unclear Mechanistic 2100.0 nM (Kd) DGIdb
LITHIUM ? unclear Mechanistic DGIdb
REPOTRECTINIB ↓ inhibits Mechanistic DGIdb
CRIZOTINIB ? unclear Mechanistic 399.0 nM (IC50) DGIdb
DOXORUBICIN HYDROCHLORIDE ? unclear Mechanistic DGIdb
UTATRECTINIB ↓ inhibits Mechanistic DGIdb
GW-2580 ? unclear Mechanistic DGIdb
CHEMBL:CHEMBL546797 ? unclear Mechanistic DGIdb
CORTICOTROPIN ? unclear Mechanistic DGIdb
CISPLATIN ? unclear Mechanistic DGIdb
ZM447439 ? unclear Mechanistic DGIdb
PLX-7486 ↓ inhibits Mechanistic DGIdb
METHADONE HYDROCHLORIDE ? unclear Mechanistic DGIdb
AST-487 ? unclear Mechanistic 190.0 nM (Kd) DGIdb
SB202190 ? unclear Mechanistic DGIdb
BMS-754807 ? unclear Mechanistic DGIdb
PILOCARPINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
HESPERADIN ↓ inhibits Mechanistic DGIdb
LESTAURTINIB ↓ inhibits Mechanistic 14.0 nM (Kd) DGIdb
TALETRECTINIB ↓ inhibits Mechanistic DGIdb
CEP-2563 DIHYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
GAMBOGIC AMIDE ? unclear Mechanistic DGIdb
LAUROGUADINE ? unclear Mechanistic DGIdb
PF-562271 ? unclear Mechanistic DGIdb
CENISERTIB ? unclear Mechanistic DGIdb
JNJ-7706621 ? unclear Mechanistic DGIdb
ALTIRATINIB ↓ inhibits Mechanistic DGIdb
ALISERTIB ? unclear Mechanistic DGIdb
TOZASERTIB ? unclear Mechanistic 240.0 nM (Kd) DGIdb
DOVITINIB ? unclear Mechanistic 720.0 nM (Kd) DGIdb

Showing top 40 of 206 agents ranked by evidence tier.

SLC6A2

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
TESOFENSINE ↓ inhibits Mechanistic DGIdb
PHENMETRAZINE ? unclear Mechanistic DGIdb
VENLAFAXINE ? unclear Mechanistic 1060.0 nM (Kd) DGIdb
SIBUTRAMINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
DEXMETHYLPHENIDATE ↓ inhibits Mechanistic DGIdb
TRIMIPRAMINE ? unclear Mechanistic DGIdb
CLOMIPRAMINE ? unclear Mechanistic DGIdb
GUANADREL SULFATE ? unclear Mechanistic DGIdb
TAPENTADOL HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
LISDEXAMFETAMINE DIMESYLATE ? unclear Mechanistic DGIdb
PROTRIPTYLINE ? unclear Mechanistic DGIdb
DESVENLAFAXINE SUCCINATE ↓ inhibits Mechanistic DGIdb
ATOMOXETINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
IOBENGUANE I-123 ? unclear Mechanistic DGIdb
SURONACRINE MALEATE ? unclear Mechanistic DGIdb
REBOXETINE ↓ inhibits Mechanistic 1.1 nM (Ki) DGIdb
BICIFADINE ↓ inhibits Mechanistic DGIdb
DOXEPIN HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
LIAFENSINE ↓ inhibits Mechanistic DGIdb
ORPHENADRINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
DULOXETINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
DASOTRALINE ↓ inhibits Mechanistic DGIdb
DESIPRAMINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
METHYLPHENIDATE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
AMITIFADINE ↓ inhibits Mechanistic DGIdb
NEFAZODONE ? unclear Mechanistic 360.0 nM (Kd) DGIdb
AMITIFADINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
DEXTROAMPHETAMINE SULFATE ? unclear Mechanistic DGIdb
TYROSINE HYDROXYLASE INHIBITOR ? unclear Mechanistic DGIdb
NORTRIPTYLINE ? unclear Mechanistic 6.3 nM (Ki) DGIdb
MAPROTILINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
ST. JOHN'S WORT ? unclear Mechanistic DGIdb
DEXTROAMPHETAMINE SACCHARATE ? unclear Mechanistic DGIdb
AMOXAPINE ↓ inhibits Mechanistic DGIdb
PHENDIMETRAZINE ↓ inhibits Mechanistic DGIdb
PHENYLPROPANOLAMINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
BUPROPION HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
BETHANIDINE ? unclear Mechanistic DGIdb
TRAMADOL ? unclear Mechanistic DGIdb
MILNACIPRAN ? unclear Mechanistic DGIdb

Showing top 40 of 269 agents ranked by evidence tier.

SLC6A3

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
ALTROPANE I-123 ? unclear Mechanistic DGIdb
BUPROPION HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
DEXMETHYLPHENIDATE ↓ inhibits Mechanistic DGIdb
AMPHETAMINE ADIPATE ? unclear Mechanistic DGIdb
DEXTROAMPHETAMINE SACCHARATE ? unclear Mechanistic DGIdb
LIAFENSINE ↓ inhibits Mechanistic DGIdb
LISDEXAMFETAMINE DIMESYLATE ? unclear Mechanistic DGIdb
METHAMPHETAMINE ↓ inhibits Mechanistic DGIdb
SIBUTRAMINE ? unclear Mechanistic DGIdb
METHYLPHENIDATE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
3,4-METHYLENEDIOXYMETHAMPHETAMINE ? unclear Mechanistic DGIdb
LEVODOPA ? unclear Mechanistic DGIdb
DEXTROAMPHETAMINE ADIPATE ? unclear Mechanistic DGIdb
METYROSINE ? unclear Mechanistic DGIdb
ANESTHETIC AGENT ? unclear Mechanistic DGIdb
SERTRALINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
BENZTROPINE ? unclear Mechanistic 312.0 nM (IC50) DGIdb
BICIFADINE ↓ inhibits Mechanistic DGIdb
ALTROPANE ? unclear Mechanistic DGIdb
DASOTRALINE ↓ inhibits Mechanistic DGIdb
DISULFIRAM ? unclear Mechanistic DGIdb
AMITIFADINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
AMPHETAMINE ASPARTATE ? unclear Mechanistic DGIdb
NICOTINE POLACRILEX ? unclear Mechanistic DGIdb
SPIROGLUMIDE ? unclear Mechanistic DGIdb
HINOKININ ? unclear Mechanistic DGIdb
DIETHYLPROPION HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
SERDEXMETHYLPHENIDATE CHLORIDE ↓ inhibits Mechanistic DGIdb
PHENTERMINE RESIN ? unclear Mechanistic DGIdb
PSEUDOEPHEDRINE ? unclear Mechanistic DGIdb
PHENMETRAZINE ? unclear Mechanistic DGIdb
CENTANAFADINE ↓ inhibits Mechanistic DGIdb
BUPRENORPHINE ? unclear Mechanistic DGIdb
PYROVALERONE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
SERDEXMETHYLPHENIDATE ↓ inhibits Mechanistic DGIdb
PHENMETRAZINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
FENCAMFAMIN ? unclear Mechanistic DGIdb
IOFLUPANE I-123 ? unclear Mechanistic DGIdb
PHENDIMETRAZINE ↓ inhibits Mechanistic DGIdb
MAZINDOL ↓ inhibits Mechanistic 42.6 nM (IC50) DGIdb

Showing top 40 of 176 agents ranked by evidence tier.

SLC6A4

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
CENTANAFADINE ↓ inhibits Mechanistic DGIdb
METHAMPHETAMINE ↓ inhibits Mechanistic DGIdb
VENLAFAXINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
LUMATEPERONE ↓ inhibits Mechanistic DGIdb
TIANEPTINE ? unclear Mechanistic DGIdb
IMIPRAMINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
ONDANSETRON HYDROCHLORIDE ? unclear Mechanistic DGIdb
PEGINTERFERON ALFA-2B ? unclear Mechanistic DGIdb
DEXFENFLURAMINE ? unclear Mechanistic DGIdb
BUPROPION HYDROCHLORIDE ? unclear Mechanistic DGIdb
CITALOPRAM ↓ inhibits Mechanistic DGIdb
TRIMIPRAMINE ? unclear Mechanistic DGIdb
VENLAFAXINE ? unclear Mechanistic DGIdb
DISULFIRAM ? unclear Mechanistic DGIdb
CHLORPHENTERMINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
PROTRIPTYLINE ? unclear Mechanistic DGIdb
MILNACIPRAN HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
CLOMIPRAMINE ? unclear Mechanistic DGIdb
NORTRIPTYLINE ? unclear Mechanistic DGIdb
DAPOXETINE ↓ inhibits Mechanistic DGIdb
AMITRIPTYLINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
TEDATIOXETINE ↓ inhibits Mechanistic DGIdb
TRAZODONE ↓ inhibits Mechanistic DGIdb
SERTRALINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
EVODIAMINE ? unclear Mechanistic DGIdb
PSEUDOEPHEDRINE ? unclear Mechanistic DGIdb
FLUOXETINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
SIBUTRAMINE ? unclear Mechanistic DGIdb
TRAMADOL ? unclear Mechanistic DGIdb
VORTIOXETINE HYDROBROMIDE ↓ inhibits Mechanistic DGIdb
BL-1021 ? unclear Mechanistic DGIdb
DOXEPIN HYDROCHLORIDE ? unclear Mechanistic DGIdb
DOTHIEPIN ↓ inhibits Mechanistic DGIdb
DEXTROMETHORPHAN POLISTIREX ? unclear Mechanistic DGIdb
DESIPRAMINE ? unclear Mechanistic DGIdb
PHENTERMINE RESIN ? unclear Mechanistic DGIdb
NORTRIPTYLINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
MONOAMINE OXIDASE INHIBITOR ? unclear Mechanistic DGIdb
MILNACIPRAN ? unclear Mechanistic DGIdb
RIBAVIRIN ? unclear Mechanistic DGIdb

Showing top 40 of 104 agents ranked by evidence tier.

Clinical Trials

Drug, biologic and supplement trials (treatment or prevention) from ClinicalTrials.gov whose main condition is Major Depressive Disorder: recruiting, active or completed, most recently updated first. Data retrieved 2026-10-28.

Double-blind, Placebo-controlled Study in Adults With Major Depressive Disorder Recruiting
NCT07226661 Phase: 2 Started: 2026-01-19

This study will evaluate the efficacy and safety of SPN-821 in adults with major depressive disorder

A Study to Evaluate the Safety and Efficacy of ALKS 7290 as an Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Recruiting
NCT07901179 Phase: 2 Started: 2026-10

The purpose of this study is to assess the efficacy, safety and tolerability of ALKS 7290 following oral administration in adult participants with Major Depressive Disorder.

Cognitive Dysfunction and Inflammation in Depression: Experimental Inhibition Via Infliximab Recruiting
NCT06136546 Phase: 2 Started: 2025-01-23

This study is a mechanistic randomized controlled trial that investigates whether inhibition of tumor necrosis factor signaling via intravenous infusion of infliximab improves psychomotor speed and executive functioning in depressed individuals who exhibit an inflammatory phenotype.

"A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder" Completed
NCT06564818 Phase: 3 Started: 2024-12-17

The purpose of this study is to examine the efficacy, safety, and tolerability of CYB003 compared to matching placebo as adjunctive treatment in participants with MDD.

A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder Recruiting
NCT06793397 Phase: 3 Started: 2025-12-10

The purpose of this study is to determine the efficacy, safety and tolerability of CYB003 compared to matching placebo as adjunctive treatment in patients with MDD. For more information about the EMBRACE study, including participating study locations, and to register your interest in learning more a...

Study of ALTO-300 in MDD Recruiting
NCT05922878 Phase: 2 Started: 2023-06-08

The purpose of this study is to determine efficacy differences between ALTO-300 and placebo, used adjunctively to an antidepressant, related to patient characteristics.

Psilocybin-assisted Therapy for Comorbid Major Depressive Disorder and Alcohol Use Disorder Recruiting
NCT07405606 Phase: 2 Started: 2026-03-23

The goal of this clinical trial is to determine the safety and efficacy of psilocybin assisted Therapy (PAT) in individuals with comorbid Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD). The main question it aims to answer is: \- What is the feasibility and safety of administering PAT...

Psychopharmacotherapy for Depressive Patients Recruiting
NCT06054321 Phase: N/A Started: 2022-08-03

The primary purpose of this study is to compare the short (12 week) and long-term (1-year) efficacy and the tolerability between stepwise psychopharmacotherapy and antidepressant monotherapy for 12 weeks in adult patients with major depressive disorders, stratified by the multimodal serum biomarker ...

NMDA Modulation in Major Depressive Disorder Recruiting
NCT04637620 Phase: 2 Started: 2017-06-01

Most of the current antidepressants for major depressive disorder (MDD) are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. NMDA hypofunction has been implicated in the pathophysiology of depression. Therefore, this study will examine the efficacy and safet...

Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression Recruiting
NCT07226232 Phase: 3 Started: 2026-08-03

The purpose of this multi-site randomized controlled trial is to evaluate the efficacy and risks of psilocybin for the treatment of depression in U.S. military Veterans with and without (±) concurrent posttraumatic stress disorder.

NMDA Modulation in Antidepressant Nonresponders With Major Depressive Disorder Recruiting
NCT05136755 Phase: 2 Started: 2022-01-25

Most of the current antidepressants for major depressive disorder (MDD) are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. NMDA hypofunction has been implicated in the pathophysiology of depression. This study aims to examine the efficacy and safety of an ...

A Phase 3 Trial of DT120 for Major Depressive Disorder (Ascend) Recruiting
NCT07592689 Phase: 3 Started: 2026-05-10

A Phase 3 Double-blind, Placebo-controlled Study (Part A) with an Open-label Extension (Part B) Evaluating DT120 Compared to Placebo in Major Depressive Disorder - Ascend

A Study to Evaluate the Maintenance Effect of Osavampator as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD) Recruiting
NCT07196501 Phase: 3 Started: 2025-08-18

The primary objective of this study is to evaluate the efficacy of osavampator (previously NBI-1065845) compared with placebo as an adjunctive treatment in delaying relapse of depressive symptoms (maintenance of effect) in participants with MDD.

Psilocybin for Major Depressive Disorder (MDD) Active Not Recruiting
NCT06308653 Phase: 3 Started: 2024-03-13

Approximately 240 eligible adult participants (≥18 years old) who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria for Major Depressive Disorder (MDD) will be enrolled. Participants will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin ...

Microdosing Psychedelics to Improve Mood Completed
NCT05259943 Phase: 2 Started: 2023-07-15

This trial aims to examine the safety and efficacy of small (2mg) sub-hallucinogenic doses of psilocybin in people with Major Depressive Disorder.

Agents Found By Disease-Level Search

Searched directly from “Major Depressive Disorder” via ClinicalTrials.gov interventions and Open Targets' disease→drug data — independent of the 14-gene target panel above. This surfaces agents whose mechanism doesn't route through a curated gene (combination therapies, standard-of-care drugs, targets outside the panel).

39 agents shown (approved or with trial evidence) — 31 not found by the gene-target search above.

escitalopram

Approved · 5 trials · source: ClinicalTrials.gov, Open Targets
NCT01034995 NCT00166114 NCT00464711

liafensine (BMS-820836)NOT in gene-target list

· 4 trials · source: ClinicalTrials.gov
NCT01369095 NCT01369095 NCT01369095

Duloxetine

Approved · 3 trials · source: ClinicalTrials.gov, Open Targets
NCT00331799 NCT01369095 NCT00062673

Fluoxetine

Approved · 2 trials · source: ClinicalTrials.gov, Open Targets
NCT00332787 NCT00018057

ELE-101NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT05434156

18FAV45NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01962753

DT-101NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07610473

Desvenlafaxine Succinate Sustained ReleaseNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00952653

MidazolamNOT in gene-target list

Phase 3 · 1 trial · source: ClinicalTrials.gov, Open Targets
NCT00952653

crinecerfont (SSR125543)NOT in gene-target list

Approved · 1 trial · source: ClinicalTrials.gov
NCT01034995

Re5 Pulsating ElectroMagnetic FieldsNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01353092

Re5 Pulsating ElectroMagnetic Fields (PEMF)NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01353092

Leveling UpNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT04324944

ZuranoloneNOT in gene-target list

Approved · 1 trial · source: ClinicalTrials.gov, Open Targets
NCT05655507

OPC-34712 + ADTNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01360632

DVS SRNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01371721

Paroxetine

Approved · 1 trial · source: ClinicalTrials.gov, Open Targets
NCT00457106

Risperidone

Phase 3 · 1 trial · source: ClinicalTrials.gov, Open Targets
NCT00457106

Apo-levocarbNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT06626152

Antidepressant medicationNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT05002309

Vortioxetine (Lu AA21004)NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01323478

Treatment as usualNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00356304

Transdiagnostic Internet-delivered REBTNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT04179526

Lumateperone

Phase 3 · 1 trial · source: ClinicalTrials.gov, Open Targets
NCT06372964

SCH 900636NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00844922

D-CycloserineNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT05591677

Desipramine

Approved · 1 trial · source: ClinicalTrials.gov, Open Targets
NCT00166114

Esketamine Treatment as Usual (ESK)NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07422519

Mindful Self CompassionNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT06646692

Treatment as Usual (TAU)NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT06646692

SeltorexantNOT in gene-target list

Phase 3 · 1 trial · source: ClinicalTrials.gov, Open Targets
NCT04513912

Quetiapine XRNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT04513912

Ketamine

Phase 3 · 1 trial · source: ClinicalTrials.gov, Open Targets
NCT06668571

Pregnenolone 500 mgNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT03645096

Pregnenolone 800 mgNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT03645096

Quetiapine Extended ReleaseNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00723970

Anyu PeiboNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT03183505

DVS-233 SRNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00075257

amibegron (SR58611A)NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00385307

Generated by the Open Source Medicine Foundation Biomarker Pipeline — 2026-10-08. Data sources: DGIdb, Open Targets, ChEMBL, PubMed, ClinicalTrials.gov. Not medical advice.