Biomarker & Intervention Discovery

Major Depressive Disorder

Pharmacologically actionable gene targets, therapeutic agents ranked by evidence tier, and active clinical trials.

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 →

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

Showing top 40 of 123 agents ranked by evidence tier.

Therapeutic Agent Effect Direction Evidence Tier Potency Source
ROSIGLITAZONE ? unclear Mechanistic
ACIVICIN inhibits Mechanistic
MEDICATION ? unclear Mechanistic
GGSTOP inhibits Mechanistic
ANTIDEPRESSANT AGENT ? unclear Mechanistic
IRX-2 ? unclear Mechanistic
ANTISERUM ? unclear Mechanistic
NALOXONE HYDROCHLORIDE ? unclear Mechanistic
CHEMBL5286255 inhibits Mechanistic 0.7 nM (Ki)
Therapeutic Agent Effect Direction Evidence Tier Potency Source
ASENAPINE ? unclear Mechanistic
MEPHENTERMINE ? unclear Mechanistic
HALOPERIDOL LACTATE inhibits Mechanistic
BREXPIPRAZOLE activates Mechanistic
ANALGESIC AGENT ? unclear Mechanistic
AXITINIB inhibits Mechanistic
RG-1530 inhibits Mechanistic
LOXAPINE SUCCINATE inhibits Mechanistic
QUETIAPINE FUMARATE inhibits Mechanistic
PROCHLORPERAZINE inhibits Mechanistic
APOMORPHINE activates Mechanistic
PRAMIPEXOLE ? unclear Mechanistic
THIETHYLPERAZINE MALEATE inhibits Mechanistic
IBCASERTIB inhibits Mechanistic
FAMITINIB inhibits Mechanistic
SOXATALTINIB inhibits Mechanistic
SUMANIROLE activates Mechanistic 9.0 nM (Ki)
DOCARPAMINE ? unclear Mechanistic
PALIPERIDONE inhibits Mechanistic
PRIDOPIDINE ~ modulates Mechanistic
OLANZAPINE inhibits Mechanistic 20.0 nM (Ki)
PEGDINETANIB inhibits Mechanistic
RISPERIDONE inhibits Mechanistic
PERGOLIDE MESYLATE activates Mechanistic
LISURIDE ? unclear Mechanistic 0.5 nM (Ki)
ZICRONAPINE ? unclear Mechanistic
CLEBOPRIDE inhibits Mechanistic
LAZERTINIB inhibits Mechanistic
REMOXIPRIDE HYDROCHLORIDE inhibits Mechanistic
CABERGOLINE activates Mechanistic
JNJ-37822681 inhibits Mechanistic
ERGOT ALKALOIDS ? unclear Mechanistic
(-)-STEPHOLIDINE ? unclear Mechanistic
SARIZOTAN HYDROCHLORIDE activates Mechanistic
5-OH-DPAT ? unclear Mechanistic
LITHIUM ? unclear Mechanistic
DIHYDROERGOTOXINE ? unclear Mechanistic
REMOXIPRIDE inhibits Mechanistic
BROMPERIDOL inhibits Mechanistic
PHENTOLAMINE ? unclear Mechanistic

Showing top 40 of 427 agents ranked by evidence tier.

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

Showing top 40 of 194 agents ranked by evidence tier.

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

Showing top 40 of 238 agents ranked by evidence tier.

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

Showing top 40 of 82 agents ranked by evidence tier.

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

Showing top 40 of 122 agents ranked by evidence tier.

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

Showing top 40 of 173 agents ranked by evidence tier.

Therapeutic Agent Effect Direction Evidence Tier Potency Source
CLORGILINE ? unclear Mechanistic
METHAMPHETAMINE ? unclear Mechanistic
ISOCARBOXAZID inhibits Mechanistic
CHEMBL:CHEMBL1927670 ? unclear Mechanistic
MEBANAZINE inhibits Mechanistic
NIALAMIDE inhibits Mechanistic
HARMINE ? unclear Mechanistic
MINAPRINE HYDROCHLORIDE inhibits Mechanistic
NAPHTHOQUINONE ? unclear Mechanistic
MOCLOBEMIDE inhibits Mechanistic
CHEMBL:CHEMBL1927684 ? unclear Mechanistic
NICOTINE POLACRILEX ? unclear Mechanistic
TRANYLCYPROMINE inhibits Mechanistic
INDANTADOL ? unclear Mechanistic
CHEMBL:CHEMBL1813518 ? unclear Mechanistic
CHEMBL:CHEMBL602466 ? unclear Mechanistic
ANTIDEPRESSANT AGENT ? unclear Mechanistic
PHENELZINE ? unclear Mechanistic
PIPERINE ? unclear Mechanistic
PARGYLINE HYDROCHLORIDE inhibits Mechanistic
CX157 ? unclear Mechanistic
IPRONIAZID inhibits Mechanistic
PHENOXYPROPAZINE inhibits Mechanistic
SELEGILINE ? unclear Mechanistic
PSORALEN ? unclear Mechanistic
TRYPTAMINE ? unclear Mechanistic
CHEMBL:CHEMBL1642672 ? unclear Mechanistic
PHENELZINE SULFATE inhibits Mechanistic
1-PHENETHYLPIPERIDINE ? unclear Mechanistic
TOLOXATONE inhibits Mechanistic
CHEMBL:CHEMBL602260 ? unclear Mechanistic
MINAPRINE inhibits Mechanistic
CHEMBL:CHEMBL2088301 ? unclear Mechanistic
PROXIBARBAL activates Mechanistic
LADOSTIGIL ? unclear Mechanistic
VITAMIN K3 ? unclear Mechanistic
CHEMBL:CHEMBL2088303 ? unclear Mechanistic
PARGYLINE ? unclear Mechanistic
TRANYLCYPROMINE SULFATE ? unclear Mechanistic
Therapeutic Agent Effect Direction Evidence Tier Potency Source
SAFINAMIDE inhibits Mechanistic 450.0 nM (Ki)
LEVODOPA ? unclear Mechanistic
CHEMBL:CHEMBL1927670 ? unclear Mechanistic
MOCLOBEMIDE inhibits Mechanistic 100000.0 nM (Ki)
CHEMBL:CHEMBL1927684 ? unclear Mechanistic
SELEGILINE inhibits Mechanistic 970.0 nM (Ki)
BIFEMELANE inhibits Mechanistic
MEBANAZINE inhibits Mechanistic
MELATONIN ? unclear Mechanistic
PARGYLINE HYDROCHLORIDE inhibits Mechanistic
CHEMBL:CHEMBL602260 ? unclear Mechanistic
ISOCARBOXAZID inhibits Mechanistic
SEROTONIN ? unclear Mechanistic
[18F]FLUORORASAGILINE ? unclear Mechanistic
RASAGILINE inhibits Mechanistic 700.0 nM (Ki)
CHEMBL:CHEMBL1642672 ? unclear Mechanistic
PHENOXYPROPAZINE inhibits Mechanistic
LAZABEMIDE inhibits Mechanistic 84.0 nM (Ki)
NIALAMIDE inhibits Mechanistic
CHEMBL:CHEMBL1813518 ? unclear Mechanistic
SAFINAMIDE MESYLATE inhibits Mechanistic
COBALAMIN ? unclear Mechanistic
PHENELZINE inhibits Mechanistic
RASAGILINE TARTRATE inhibits Mechanistic
RALFINAMIDE inhibits Mechanistic
SELEGILINE HYDROCHLORIDE inhibits Mechanistic
VITAMIN K3 ? unclear Mechanistic
CHEMBL:CHEMBL2088303 ? unclear Mechanistic
TRANYLCYPROMINE inhibits Mechanistic
PARGYLINE ? unclear Mechanistic 1800.0 nM (Ki)
ANTIDEPRESSANT AGENT ? unclear Mechanistic
MOFEGILINE ? unclear Mechanistic
INDANTADOL ? unclear Mechanistic
NAPHTHOQUINONE ? unclear Mechanistic
METHAMPHETAMINE ? unclear Mechanistic
HALOPERIDOL DECANOATE ? unclear Mechanistic
PHENELZINE SULFATE inhibits Mechanistic
IPRONIAZID inhibits Mechanistic 7540.0 nM (IC50)
LINEZOLID inhibits Mechanistic
CHEMBL:CHEMBL602466 ? unclear Mechanistic

Showing top 40 of 218 agents ranked by evidence tier.

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

Showing top 40 of 206 agents ranked by evidence tier.

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

Showing top 40 of 269 agents ranked by evidence tier.

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

Showing top 40 of 176 agents ranked by evidence tier.

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

Showing top 40 of 104 agents ranked by evidence tier.


Clinical Trials

Recruiting and recently completed trials from ClinicalTrials.gov. Data retrieved 2026-07-06.

No recent clinical trials found on ClinicalTrials.gov for this condition.


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).

60 agents shown (approved or with trial evidence) — 51 not found by the gene-target search above.

escitalopram

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

BMS-820836NOT in gene-target list

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

Duloxetine

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

Placebo + ADTNOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT01360632 NCT01360632

Fluoxetine

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

Cognitive Behavioral TherapyNOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT00018057 NCT02883257

ELE-101NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT05434156

ELE-101 PlaceboNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT05434156

18FAV45NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01962753

Transcranial Magnetic StimulationNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT06719427

DT-101NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07610473

Exercise -RunningNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT05837351

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

SSR125543NOT in gene-target list

· 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

Collaborative Decision Skills TrainingNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT04324944

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

High frequency stimulationNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT02184221

Low frequency stimulationNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT02184221

OPC-34712 + ADTNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01360632

Accelerated HF-rTMS (Magstim Rapid 2 stimulator)NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT02125799

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

Repetitive Transcranial Magnetic StimulationNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00104611

Cognitive-Behavioural TherapyNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT05002309

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

Motivational interviewingNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00356304

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

Attention Bias Modification TrainingNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00018057

D-CycloserineNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT05591677

Intermittent Theta Burst StimulationNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT05591677

Desipramine

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

Expectation confirmationNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT03780881

Expectation disconfirmationNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT03780881

Virtual-Reality-based mindfulness interventionNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07422519

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

Matching placebo to SeltorexantNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT04513912

Quetiapine XRNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT04513912

Matching placebo to Quetiapine XRNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT04513912

Ketamine

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

Normal Saline

· 1 trial · source: ClinicalTrials.gov
NCT06668571

BMS-820836 PlaceboNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01369095

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

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