This is a list of investigational antidepressants, or drugs that are currently under development for clinical use in the treatment of depression but are not yet approved. Specific indications include major depressive disorder, treatment-resistant depression, dysthymia, bipolar depression, and postpartum depression, among others.
Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses.
This list was last comprehensively updated in August 2024. It is likely to become outdated with time.
Under development Phase 3 Cycloserine/lurasidone (Cyclurad; NRX-101) – ionotropic glutamate NMDA receptor glycine site partial agonist and atypical antipsychotic (non-selective monoamine receptor modulator) combination Deupsilocin (HLP003; HLP-003; CYB003; CYB-003; deuterated psilocybin analogue; deuterated psilocin) – serotonin 5-HT2A receptor agonist and psychedelic hallucinogen Esmethadone (dextromethadone; REL-1017) – ionotropic glutamate NMDA receptor antagonist and other actions Ketamine (HTX-100; NRX-100) – ionotropic glutamate NMDA receptor antagonist Lysergic acid diethylamide (LSD; MM-120) – non-selective serotonin receptor agonist and psychedelic hallucinogen Navacaprant (BTRX-140; BTRX-335140; CYM-53093; NMRA-140; NMRA-335140) – κ-opioid receptor antagonist Osavampator (TAK-653; NBI-1065845; NBI-845) – ionotropic glutamate AMPA receptor positive allosteric modulator Pimavanserin (ACP-103; BVF-048; Nuplazid) – serotonin 5-HT2A and 5-HT2C receptor antagonist or inverse agonist Psilocybin (COMP-360) – non-selective serotonin receptor agonist and psychedelic hallucinogen Psilocybin (Usona Institute) – non-selective serotonin receptor agonist and psychedelic hallucinogen Seltorexant (JNJ-42847922; JNJ-7922; MIN-202) – orexin OX2 receptor antagonist SEP-4199 (non-racemic amisulpride; aramisulpride/esamisulpride [85:15 ratio]) – atypical antipsychotic (dopamine D2 and D3 receptor antagonist and serotonin 5-HT2B and 5-HT7 receptor antagonist) SNG-12 (Synapsinae) – glycine transporter 1 (GlyT1) inhibitor Solriamfetol (Sunosi; JZP-110; SKLN05; ARL-N05; YKP-10A; R-228060; ADX-N05) – norepinephrine and dopamine reuptake inhibitor and trace amine-associated receptor 1 (TAAR1) agonist Ulotaront (SEP-363856; SEP-856) – serotonin 5-HT1A receptor agonist and trace amine-associated receptor 1 (TAAR1) agonist
Phase 2/3 PRAX-114 – extrasynaptic GABAA receptor-preferring positive allosteric modulator and neurosteroid
Phase 2 4-Chlorokynurenine (4-CL-KYN; AV-101) – ionotropic glutamate NMDA receptor glycine site antagonist and kynurenine modulator Ademetionine (MSI-190; MSI-195; S-Adenosyl-L-Methionine; Sam-E; SAMe; Strada) – cofactor in monoamine neurotransmitter biosynthesis ALTO-203 – histamine H3 receptor inverse agonist Amdiglurax (ALTO-100, NSI-189) – unknown mechanism of action (hippocampal neurogenesis stimulant and indirect brain-derived neurotrophic factor (BDNF) modulator) Apimostinel (AGN-241660; GATE-202; NRX-1074) – ionotropic glutamate NMDA receptor glycine site partial agonist Arketamine ((R)-ketamine; PCN-101) – ionotropic glutamate NMDA receptor antagonist Azetukalner (1OP-2198; encukalner; VRX-621698; XEN-1101; XPF-008) – KCNQ potassium channel agonist BI-1358894 – transient receptor potential cation TRPC4 and TRPC5 channel inhibitor BI-1569912 – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator Blixeprodil (GM-1020; (R)-4-fluorodeschloroketamine ((R)-4-FDCK) – ionotropic glutamate NMDA receptor antagonist Bretisilocin (GM-2505; 5F-MET; 5-fluoro-N-methyl-N-ethyltryptamine) – serotonin 5-HT2A and 5-HT2C receptor agonist, serotonin 5-HT2B receptor antagonist, psychedelic hallucinogen, and serotonin releasing agent Brezivaptan (ANC-501; THY-1773; TS-1211; TS-121) – vasopressin V1b receptor antagonist CB-03 (CB-04; CB-003; CB03-154) – KCNQ2 and KCNQ3 potassium channel stimulant Centanafadine (CTN; EB-1020) – serotonin, norepinephrine, and dopamine reuptake inhibitor Deudextromethorphan/quinidine (AVP-786; CTP-786; d-DM/Q; d6-DM/Q; deuterated dextromethorphan/ultra-low-dose quinidine) – sigma σ1 receptor agonist, serotonin reuptake inhibitor, ionotropic glutamate NMDA receptor antagonist, other actions, and CYP2D6 inhibitor combination Dimethyltryptamine (N,N-Dimethyltryptamine; DMT; N,N-DMT; BMND-01; BMND-02; BMND-03) – non-selective serotonin receptor agonist and psychedelic hallucinogen Elunetirom (ABX-002; MA-JD21; LL-340001 prodrug) – thyroid hormone receptor β (TRβ) agonist Emestedastat (UE-2343; Xanamem) – 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor (glucocorticoid synthesis inhibitor) Esketamine (CLE-100) – ionotropic glutamate NMDA receptor antagonist FKB-01MD (FKB01MD; TGBA-01AD; TGBA01AD) – serotonin reuptake inhibitor, serotonin 5-HT1A receptor agonist, serotonin 5-HT1D receptor modulator, and serotonin 5-HT2 receptor agonist Forvisirvat (SP-624) – sirtuin 6 (SIRT6) stimulant Itruvone (PH-10; PH-10A; PH10-NS) – chemoreceptor cell stimulant, vomeropherine, and neurosteroid JNJ-54175446 (JNJ-5446) – purinergic P2X7 receptor antagonist JNJ-55308942 – purinergic P2X7 receptor antagonist Ketamine (extended-release; R-107; R107) – ionotropic glutamate NMDA receptor antagonist Ketamine (intranasal; Ereska; PMI-100; PMI-150; SLS-002; TUR-002) – ionotropic glutamate NMDA receptor antagonist Ketamine (prolonged-release oral; KET-01) – ionotropic glutamate NMDA receptor antagonist Liafensine (BMS-820836; DB-104) – serotonin, norepinephrine, and dopamine reuptake inhibitor Lisdexamfetamine (Vyvanse) – norepinephrine and dopamine releasing agent Lithium cocrystal (AL-001; LiProSal; lithium salicylate L-proline ionic cocrystal) – unknown mechanism of action and mood stabilizer (improved formulation of lithium) Luvesilocin (RE-104/RE104, FT-104/FT104; 4-HO-DiPT/iprocin prodrug) – serotonin 5-HT2A receptor agonist and psychedelic hallucinogen Lysergic acid diethylamide (LSD; MB-22001) – non-selective serotonin receptor agonist and psychedelic hallucinogen Mebufotenin (5-MeO-DMT; 5-Methoxy-N,N-Dimethyltryptamine; BPL-002; BPL-003) – non-selective serotonin receptor agonist and psychedelic hallucinogen Mefluleucine (NV-5138; SPN-820/SPN-821) – sestrin2 modulator and mammalian target of rapamycin complex 1 (mTORC1) stimulant Mifepristone (Mifeprex; RU-38486; RU-486) – progesterone receptor antagonist, glucocorticoid receptor antagonist, and androgen receptor antagonist NBI-1070770 – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator Nelivaptan (SR-149415; BH-200) – vasopressin V1B receptor antagonist NORA-520 (brexanolone prodrug) – GABAA receptor positive allosteric modulator and neurosteroid Onabotulinum toxin A (BoNTA; Botox; Botulinum toxin A injectable; GSK-1358820; OnabotA X; onabotulinumtoxinA X; Vistabel; Vistabex) – acetylcholine release inhibitor and neuromuscular blocking agent Onfasprodil (CAD-9271; MIJ-821; MIJ821) – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator ONO-1110 – endocannabinoid synthesis regulator and indirect cannabinoid receptor modulator Opakalim (BHV-7000; BPN-25203; KB-3061) – KCNQ potassium channel agonist OPC-64005 – serotonin, norepinephrine, and dopamine reuptake inhibitor OSU-6162 (PNU-9639; PNU-96391; PNU-96391A) – serotonin 5-HT2A receptor partial agonist (non-hallucinogenic), dopamine D2 receptor partial agonist, and sigma σ1 receptor ligand (so-called "monoaminergic stabilizer") PDC-1421 (ABV-1504; ABV-1505; ABV-1601; BLI-1005) – norepinephrine reuptake inhibitor Pegipanermin (DN-TNF; INB-03; LIVNate; Quellor; XENP-1595; XENP-345; XPro-1595; XPro595; XPro) – tumor necrosis factor α (TNFα) inhibitor PIPE-307 (JNJ-5120; JNJ-89495120) – muscarinic acetylcholine M1 receptor antagonist Pramipexole (CTC-413; CTC-501) – dopamine D2, D3, and D4 receptor agonist Pramipexole/ondansetron (ALTO-207, CTC-501) – combination of pramipexole (dopamine D2-like receptor agonist) and ondansetron (serotonin 5-HT3 receptor antagonist) Pregnenolone methyl ether (3β-methoxypregnenolone; MAP-4343) – microtubule-associated protein (MAP) stimulant and tubulin polymerization promoter Ralmitaront (RG-7906; RO-6889450) – trace amine-associated receptor 1 (TAAR1) agonist Rislenemdaz (AVTX-301; CERC-301; MK-0657) – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator Ropanicant (SUVN-911) – α4β2 nicotinic acetylcholine receptor antagonist Tebideutorexant (JNJ-61393215; JNJ-3215) – orexin OX1 receptor antagonist Tildacerfont (SPR-001; LY-2371712) – corticotropin releasing factor receptor 1 (CRF1) antagonist Tramadol (controlled-release; ETS-6103; ETX-6103; Viotra) – μ-opioid receptor agonist, serotonin and norepinephrine reuptake inhibitor, serotonin 5-HT2C receptor antagonist, and other actions TS-161 – metabotropic glutamate mGlu2 and mGlu3 receptor antagonist Zelquistinel (AGN-241751; GATE-251) – ionotropic glutamate NMDA receptor partial positive allosteric modulator
Phase 1/2 PT-00114 (PT100114) – corticotropin releasing hormone (CRH) inhibitor
Phase 1 ACD856 (ACD-856) – tropomyosin receptor kinase TrkA, TrkB, and TrkC positive allosteric modulator Agomelatine (ALTO-300; agomelatine 25mg formulation) – serotonin 5-HT2C receptor antagonist and melatonin MT1 and MT2 receptor agonist BMND07 (BMND-07; dimethyltryptamine or 5-MeO-DMT combination drug) – non-selective serotonin receptor agonist, serotonergic hallucinogen, and other actions combination BRII-296 (extended-release injectable aqueous suspension formulation of brexanolone) – GABAA receptor positive allosteric modulator and neurosteroid Brilaroxazine (RP-5000; RP-5063) – atypical antipsychotic (non-selective monoamine receptor modulator) Carbidopa/oxitriptan (EVX-101) – serotonin precursor (5-hydroxytryptophan; 5-HTP) and aromatic L-amino acid decarboxylase (AAAD) inhibitor combination Crisdesalazine (AAD-2004) – microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitor DGX-001 (ZZ-2103) – gastrointestinally selective vasopressin V1A receptor agonist, peptide, and gut–brain axis modulator Dimethyltryptamine (N,N-dimethyltryptamine; DMT; N,N-DMT; VLS-01) – non-selective serotonin receptor agonist and psychedelic hallucinogen DSP-3456 – metabotropic glutamate mGlu2 and mGlu3 receptor negative allosteric modulator Ebselen (DR-3305; Harmokisane; PZ-51; SPI-1005; SPI-3005) – multiple mechanisms of action ENX-205 – dopamine D2 and D3 receptor antagonist and serotonin 5-HT1A and 5-HT2A receptor agonist Icalcaprant (CVL-354) – κ-opioid receptor antagonist KAR-2618 (GFB-887) – transient receptor potential cation TRPC4 and TRPC5 channel inhibitor SAL-0114 – undefined mechanism of action Scopolamine (DPI-385-CVS; DPI-386; DPI-386 Nasal Gel; DPI-386-SG; DPI-386-SS; DPI-387; DPI-521-CG; DPI-550-TBI; INSCOP spray) – non-selective muscarinic acetylcholine receptor antagonist Traneurocin (NA-831; Cycloprolylglycine; CPG) – unknown or undefined / ionotropic glutamate AMPA receptor positive allosteric modulator, GABAA receptor positive allosteric modulator, and racetam-like drug XW-10508 (oral esketamine conjugate prodrug) – ionotropic glutamate NMDA receptor antagonist Zalsupindole (DLX-001; DLX-1; AAZ; AAZ-A-154) – non-hallucinogenic serotonin 5-HT2A receptor agonist
Preclinical 2-Bromo-LSD (bromolysergide; BETR-001, TD-0148A) – non-hallucinogenic serotonin 5-HT2A receptor agonist and other actions AKO-003 (ketamine-based psychedelic formulation; ketamine/specific plant bioactive) – ionotropic glutamate NMDA receptor antagonist, dissociative hallucinogen, and "specific plant bioactive" combination ALTO-202 – NR2B subunit-containing ionotropic glutamate NMDA receptor antagonist