# List of investigational antidepressants

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 It is likely to become outdated with time.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
### Preregistration

* Buprenorphine/samidorphan (ALKS-5461) – μ-opioid receptor partial agonist, κ-opioid receptor antagonist, δ-opioid receptor antagonist, and μ-opioid receptor antagonist combination – New Drug Application (NDA) rejected in 2019, no updates since 2021

### Phase 3

* Aticaprant (AVTX-501; CERC-501; JNJ-3964; JNJ-67953964; LY-2456302) – κ-opioid receptor antagonist
* CYB003 (CYB-003; deuterated psilocybin analogue) – serotonin 5-HT$_{2A}$ receptor agonist and psychedelic hallucinogen
* Cycloserine/lurasidone (Cyclurad; NRX-101) – ionotropic glutamate NMDA receptor glycine site partial agonist and atypical antipsychotic (non-selective monoamine receptor modulator) combination
* Esmethadone (dextromethadone; REL-1017) – ionotropic glutamate NMDA receptor antagonist and other actions
* Ketamine (HTX-100; NRX-100) – ionotropic glutamate NMDA receptor antagonist
* Navacaprant (BTRX-140; BTRX-335140; CYM-53093; NMRA-140; NMRA-335140) – κ-opioid receptor antagonist
* Pimavanserin (ACP-103; BVF-048; Nuplazid) – serotonin 5-HT$_{2A}$ receptor antagonist or inverse agonist
* Psilocybin (COMP-360) – non-selective serotonin receptor agonist and psychedelic hallucinogen
* Seltorexant (JNJ-42847922; JNJ-7922; MIN-202) – orexin OX$_2$ receptor antagonist
* SEP-4199 (non-racemic amisulpride; aramisulpride/esamisulpride [85:15 ratio]) – atypical antipsychotic (dopamine D$_2$ and D$_3$ receptor antagonist and serotonin 5-HT$_{2B}$ and 5-HT$_7$ 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-HT$_{1A}$ receptor agonist and trace amine-associated receptor 1 (TAAR1) agonist

### Phase 2/3

* PRAX-114 – extrasynaptic GABA$_A$ 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-100 (NSI-189) – unknown mechanism of action (hippocampal neurogenesis stimulant and indirect brain-derived neurotrophic factor (BDNF) modulator)
* ALTO-203 – histamine H$_3$ receptor agonist
* 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
* BHV-7000 (BPN-25203; KB-3061) – KCNQ2 potassium channel stimulant
* BI-1358894 – transient receptor potential cation TRPC4 and TRPC5 channel inhibitor
* 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-HT$_{2A}$ and 5-HT$_{2C}$ receptor agonist, serotonin 5-HT$_{2B}$ receptor antagonist, psychedelic hallucinogen, and serotonin releasing agent
* Brezivaptan (ANC-501; THY-1773; TS-1211; TS-121) – vasopressin V$_{1b}$ receptor antagonist
* 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 σ$_1$ 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
* 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-HT$_{1A}$ receptor agonist, serotonin 5-HT$_{1D}$ receptor modulator, and serotonin 5-HT$_2$ receptor agonist
* Itruvone (PH-10; PH-10A; PH10-NS) – chemoreceptor cell stimulant, vomeropherine, and neurosteroid
* JNJ-54175446 (JNJ-5446) – purinergic P2X$_7$ receptor antagonist
* JNJ-55308942 – purinergic P2X$_7$ 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
* 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
* 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
* NORA-520 (brexanolone prodrug) – GABA$_A$ 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
* OPC-64005 – serotonin, norepinephrine, and dopamine reuptake inhibitor
* Osavampator (TAK-653; NBI-1065845; NBI-845) – ionotropic glutamate AMPA receptor positive allosteric modulator
* OSU-6162 (PNU-9639; PNU-96391; PNU-96391A) – serotonin 5-HT$_{2A}$ receptor partial agonist (non-hallucinogenic), dopamine D$_2$ receptor partial agonist, and sigma σ$_1$ 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
* Pramipexole (CTC-413; CTC-501) – dopamine D$_2$, D$_3$, and D$_4$ receptor agonist
* 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
* RE-104 (FT-104; 4-HO-DiPT/iprocin prodrug) – serotonin 5-HT$_{2A}$ receptor agonist and psychedelic hallucinogen
* Rislenemdaz (AVTX-301; CERC-301; MK-0657) – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator
* Ropanicant (SUVN-911) – α$_4$β$_2$ nicotinic acetylcholine receptor antagonist
* SP-624 – sirtuin 6 (SIRT6) stimulant
* SPN-820 (NV-5138; SPN-821) – sestrin2 modulator and mammalian target of rapamycin complex 1 (mTORC1) stimulant
* Tebideutorexant (JNJ-61393215; JNJ-3215) – orexin OX$_1$ receptor antagonist
* Tildacerfont (SPR-001; LY-2371712) – corticotropin releasing factor receptor 1 (CRF$_1$) antagonist
* Tramadol (controlled-release; ETS-6103; ETX-6103; Viotra) – μ-opioid receptor agonist, serotonin and norepinephrine reuptake inhibitor, serotonin 5-HT$_{2C}$ receptor antagonist, and other actions
* TS-161 – metabotropic glutamate mGlu$_2$ and mGlu$_3$ 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

* ABX-002 (LL-340001 prodrug) – thyroid hormone receptor β (TRβ) agonist
* Agomelatine (ALTO-300; agomelatine 25 mg formulation) – serotonin 5-HT$_{2C}$ receptor antagonist and melatonin MT$_1$ and MT$_2$ receptor agonist
* BI-1569912 – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator
* 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) – GABA$_A$ 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 – 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 mGlu$_2$ and mGlu$_3$ receptor negative allosteric modulator
* Ebselen (DR-3305; Harmokisane; PZ-51; SPI-1005; SPI-3005) – multiple mechanisms of action
* Icalcaprant (CVL-354) – κ-opioid receptor antagonist
* KAR-2618 (GFB-887) – transient receptor potential cation TRPC4 and TRPC5 channel inhibitor
* PIPE-307 – muscarinic acetylcholine M$_1$ receptor antagonist
* 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, GABA$_A$ 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-HT$_{2A}$ receptor agonist

### Preclinical

* 2-Bromo-LSD (bromolysergide; BETR-001, TD-0148A) – non-hallucinogenic serotonin 5-HT$_{2A}$ receptor agonist and other actions
* ACD856 (ACD-856) – tropomyosin receptor kinase TrkA, TrkB, and TrkC positive allosteric modulator
* 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
* Brexpiprazole (long-acting injectable; MTD-211) – atypical antipsychotic (non-selective monoamine receptor modulator)
* CB-03 (CB-04; CB-003; CB03-154) – KCNQ2 and KCNQ3 potassium channel stimulant
* CRHR1 antagonist therapeutic (HMNC Brain Health) – corticotropin releasing factor receptor 1 (CRF$_1$) antagonist
* Duloxetine (oral suspension) – serotonin and norepinephrine reuptake inhibitor
* EB-003 – non-hallucinogenic serotonin receptor agonist and psychoplastogen
* EGX-A – serotonin 5-HT$_{2A}$ receptor agonist and psychedelic hallucinogen
* EGX-B – serotonin 5-HT$_{2A}$ receptor agonist and psychedelic hallucinogen
* ENX-104 – presynaptic dopamine D$_2$ and D$_3$ autoreceptor antagonist (at low doses)
* ENX-105 – dopamine D$_2$ and D$_3$ receptor antagonist and serotonin 5-HT$_{1A}$ and 5-HT$_{2A}$ receptor agonist (non-hallucinogenic)
* Etifoxine deuterated (GRX-917) – GABA$_A$ receptor positive allosteric modulator and translocator protein (TSPO; peripheral benzodiazepine receptor) agonist (neurosteroidogenesis stimulant)
* GABA positive allosteric modulator (CS Bay Therapeutics) – GABA$_A$ receptor positive allosteric modulator
* INV-88 – macrophage migration inhibitory factor (MIF) inhibitor
* ITI-333 – serotonin 5-HT$_{2A}$ receptor antagonist, μ-opioid receptor biased partial agonist, α$_{1A}$-adrenergic receptor antagonist, and dopamine D$_1$ receptor antagonist
* ITI-1549 – non-hallucinogenic serotonin 5-HT$_{2A}$ receptor agonist and serotonin 5-HT$_{2B}$ receptor antagonist
* Ketamine (depot; ALA-3000) – ionotropic glutamate NMDA receptor antagonist
* Lithium cocrystal (AL-001; LiProSal; lithium salicylate L-proline ionic cocrystal) – unknown mechanism of action and mood stabilizer (improved formulation of lithium)
* LPH-5 – selective serotonin 5-HT$_{2A}$ receptor partial agonist and psychedelic hallucinogen
* LPCN-1154 (LPCN1154; oral brexanolone) – GABA$_A$ receptor positive allosteric modulator and neurosteroid
* Lucid-PSYCH (Lucid-201) – undefined mechanism of action and psychedelic hallucinogen
* Mebufotenin (5-MeO-DMT; 5-methoxy-N,N-dimethyltryptamine; LSR-1019) – non-selective serotonin receptor agonist and psychedelic hallucinogen
* Midomafetamine (microneedle transdermal patch; 3,4-methylenedioxymethamphetamine; MDMA) – serotonin, norepinephrine, and dopamine releasing agent and weak serotonin 5-HT$_{2A}$, 5-HT$_{2B}$, and 5-HT$_{2C}$ receptor agonist (entactogen and weak psychedelic hallucinogen)
* Nezavist – GABA$_A$ receptor positive allosteric modulator
* NLX-101 (F-15599) – serotonin 5-HT$_{1A}$ receptor full agonist
* PSIL-001 (DMT analogue) – serotonin 5-HT$_1$ receptor modulator (non-hallucinogenic)
* PSIL-002 (DMT analogue) – serotonin 5-HT$_1$ receptor modulator (non-hallucinogenic)
* PSYLO-3001 (Psylo-3001) – non-hallucinogenic non-selective serotonin receptor agonist and psychoplastogen
* PSYLO-4001 (Psylo-4001) – non-hallucinogenic serotonin 5-HT$_{2A}$ receptor agonist and psychoplastogen
* SYT-510 – endocannabinoid reuptake inhibitor
* TF-0066 – undefined mechanism of action

### Research

* BHV-5000 – low-trapping ionotropic glutamate NMDA receptor antagonist
* NP-10679 – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator
* Psilocybin (MYCO-001; MYCO-003) – non-selective serotonin receptor agonist and psychedelic hallucinogen
* PSYLO-5001 (Psylo-5001) – non-hallucinogenic serotonin 5-HT$_{2A}$ receptor agonist and psychoplastogen
* Small molecule therapeutic - Rugen Therapeutics – undefined mechanism of action

### Phase unknown

* Amuxetine – serotonin, norepinephrine, and dopamine reuptake inhibitor
* EDG-005 – undefined mechanism of action
* EDG-006 – undefined mechanism of action
* Iloperidone (Fanapt; Fanaptum; Fiapta; HP-873; ILO-522; VYV-683; Zomaril) – atypical antipsychotic (non-selective monoamine receptor modulator)
* INV-407 – undefined mechanism of action
* Ketamine (intravenous/oral; Braxia) – ionotropic glutamate NMDA receptor antagonist
* SK-2110 (buprenorphine implant) – μ-opioid receptor partial agonist, κ-opioid receptor antagonist, and δ-opioid receptor antagonist – under development in China
* Venlafaxine (controlled-release) – serotonin and norepinephrine reuptake inhibitor

## Not under development
### Development suspended

* BVF-045 (bupropion/undisclosed serotonin reuptake inhibitor) – norepinephrine and dopamine reuptake inhibitor, nicotinic acetylcholine receptor negative allosteric modulator, and serotonin reuptake inhibitor combination
* Dexmedetomidine (BXCL-501; Igalmi; KalmPen) – α$_2$-adrenergic receptor agonist
* ETX-155 – GABA$_A$ receptor positive allosteric modulator
* Ganaxolone (CCD-1042; Ztalmy) – GABA$_A$ receptor positive allosteric modulator and neurosteroid

### No development reported

* AAG-561 – corticotropin releasing hormone (CRH) inhibitor
* Adinazolam (Deracyn; U-41123; U-41123F) – GABA$_A$ receptor positive allosteric modulator and benzodiazepine
* Amitifadine (DOV-21947; EB-1010) – serotonin, norepinephrine, and dopamine reuptake inhibitor
* AN-788 (NSD-788) – serotonin and dopamine reuptake inhibitor
* ANAVEX 1-41 (blarcamesine analogue) – sigma σ$_1$ receptor agonist, muscarinic acetylcholine receptor modulator, and sodium and chloride channel modulator
* Aripiprazole (transdermal; AQS-1301) – atypical antipsychotic (non-selective monoamine receptor modulator)
* Arketamine (HR-071603; (R)-ketamine nasal spray) – ionotropic glutamate NMDA receptor antagonist
* AZD-8108 – ionotropic glutamate NMDA receptor antagonist
* BCI-632 – metabotropic glutamate mGlu$_2$ and mGlu$_3$ receptor antagonist
* BCI-838 – metabotropic glutamate mGlu$_2$ and mGlu$_3$ receptor antagonist
* BMS-866949 (CSTI-500) – serotonin, norepinephrine, and dopamine reuptake inhibitor
* Bryostatin 1 (MW-904) – protein kinase C (PKC) stimulant
* BTRX-246040 (LY-2940094) – nociceptin receptor antagonist
* Bupropion/naltrexone (Contrave) – norepinephrine and dopamine reuptake inhibitor, nicotinic acetylcholine receptor negative allosteric modulator, and μ-opioid receptor antagonist combination
* Cericlamine (JO-1017) – serotonin reuptake inhibitor
* Citalopram/pipamperone (PipCit; PNB-01) – serotonin reuptake inhibitor and typical antipsychotic combination
* Depression therapy - Genopia Biomedical – undefined mechanism of action
* (R)-Desmethylsibutramine ((+)-desmethylsibutramine; or (R)-desmethylsibutramine/(+)-didesmethylsibutramine) – serotonin, norepinephrine, and dopamine reuptake inhibitor
* Deulumateperone (ITI-1284; lumateperone deuterated) – atypical antipsychotic (non-selective monoamine receptor modulator)
* Dipraglurant (ADX-48621; mGluR5-NAM) – metabotropic glutamate mGlu$_5$ receptor negative allosteric modulator
* Erteberel (LY-500307; SERBA-1) – estrogen receptor β (ERβ) agonist
* Esketamine (esketamine DPI; Falkieri; PG061; S-ketamine) – ionotropic glutamate NMDA receptor antagonist
* Eszopiclone (Lunesta) – GABA$_A$ receptor positive allosteric modulator and Z-drug
* EVT-101 (ENS-101) – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator
* Fananserin (RP-62203) – serotonin 5-HT$_{2A}$ receptor antagonist and dopamine D$_4$ receptor antagonist
* Fibroblast growth factor 1 (FGF-1) – fibroblast growth factor receptor (FGFR) agonist
* Filorexant (MK-6096) – orexin OX$_1$ and OX$_2$ receptor antagonist
* GEA-857 (alaproclate analogue) – potassium conductance putative blocker
* GSK-588045 – serotonin 5-HT$_{1A}$, 5-HT$_{1B}$, and 5-HT$_{1D}$ receptor antagonist
* GSK-1360707 – serotonin, norepinephrine, and dopamine reuptake inhibitor
* HS-10353 – GABA$_A$ receptor positive allosteric modulator
* Hypidone – serotonin reuptake inhibitor and serotonin 5-HT$_{1A}$ and 5-HT$_6$ receptor agonist
* Igmesine (CI-1019; JO-1784) – sigma σ$_1$ receptor agonist
* Imiloxan (RS-21361) – α$_2$-adrenergic receptor antagonist
* IN-ASTR-001 – undefined mechanism of action
* Ketamine (transdermal patch; SHX-001) – ionotropic glutamate NMDA receptor antagonist
* Ketamine (sublingual; ketamine wafer; SLS-003; Wafermine) – ionotropic glutamate NMDA receptor antagonist
* KFM-19 – adenosine A$_1$ receptor antagonist
* LSM-6 (3-hydroxy-N,N-dimethylphenethylamine) – undefined mechanism of action (adrenergic and serotonergic agent; constituent of Limacia scanden Lour.) – was under development in Malaysia
* Midomafetamine (3,4-methylenedioxymethamphetamine; MDMA; ecstasy) – serotonin, norepinephrine, and dopamine releasing agent and weak serotonin 5-HT$_{2A}$, 5-HT$_{2B}$, and 5-HT$_{2C}$ receptor agonist (entactogen and weak psychedelic hallucinogen)
* Mitizodone (HEC-113995) – serotonin reuptake inhibitor and serotonin 5-HT$_{1A}$ and 5-HT$_{1B}$ receptor partial agonist
* Nivacortol (nivazole; NEBO-174; novozola) – glucocorticoid receptor antagonist
* Omiloxetine – serotonin reuptake inhibitor
* Oxitriptan (5-hydroxytryptophan; 5-HTP; EVX-301) – serotonin precursor
* Pseudohypericin – undefined mechanism of action (constituent of St John's wort)
* Psilocybin (CYB-001; INT0052/2020) – non-selective serotonin receptor agonist and psychedelic hallucinogen
* Psilocybin (biosynthetic psilocybin; PB-1818) – non-selective serotonin receptor agonist and psychedelic hallucinogen
* QRX-002 – ionotropic glutamate NMDA receptor antagonist
* RG-7351 – trace amine-associated receptor 1 (TAAR1) agonist
* Riluzole (sublingual; BHV-0223; Nurtec) – complex mechanism of action or glutamatergic modulator
* Risperidone (Risperdal) – atypical antipsychotic (non-selective monoamine receptor modulator)
* SAR-102779 (SAR-10279) – neurokinin NK$_2$ receptor antagonist
* SD-254 (deuterated venlafaxine) – serotonin and norepinephrine reuptake inhibitor
* SEP-378614 – undefined mechanism of action
* SNA-1 – undefined mechanism of action
* Soclenicant (BNC-210; IW-2143) – α$_7$ nicotinic acetylcholine receptor negative allosteric modulator
* SPL-801-B ((2R,6R)-hydroxynorketamine; 6-HNK) – non-hallucinogenic ketamine derivative/metabolite
* TrkB receptor antagonist (Celon Pharma) – tropomyosin receptor kinase TrkB antagonist
* YDP-2225 – undefined mechanism of action

### Development discontinued

* ABT-436 – vasopressin V$_{1b}$ receptor antagonist
* Adatanserin (WAY-SEB-324; WY-50324; SEB-324) – serotonin 5-HT$_{1A}$ receptor partial agonist and serotonin 5-HT$_{2A}$ and 5-HT$_{2C}$ receptor antagonist
* ADX-71149 (JNJ-1813; JNJ-40411813; JNJ-mGluR2-PAM) – metabotropic glutamate mGlu$_2$ receptor modulator
* Amesergide (LY-237733) – serotonin 5-HT$_{2A}$, 5-HT$_{2B}$, and 5-HT$_{2C}$ receptor antagonist, α$_2$-adrenergic receptor antagonist, and other actions
* Amibegron (SR-58611; SR-58611A) – β$_3$-adrenergic receptor agonist
* Aprepitant (MK-869) – neurokinin NK$_1$ receptor antagonist
* ARA-014418 (AR-A014418; GSK-3β Inhibitor VIII) – glycogen synthase kinase GSK-3β inhibitor
* Armodafinil (CEP-10953; Nuvigil; (R)-modafinil) – atypical dopamine reuptake inhibitor
* Atipamezole (antisedan; MPV-1248) – α$_2$-adrenergic receptor antagonist
* Atomoxetine (LY-139603; Strattera; Tomoxetine) – norepinephrine reuptake inhibitor
* AZD-2066 – metabotropic glutamate mGlu$_5$ receptor antagonist
* AZD-2327 – δ-opioid receptor agonist
* AZD-7268 – δ-opioid receptor agonist
* AZD-8129 (AR-A000002; AR-A2XX; AR-A2) – serotonin 5-HT$_{1B}$ receptor antagonist
* Basimglurant (NOE-101; RG-7090; RO-4917523) – metabotropic glutamate mGlu$_5$ receptor antagonist
* Befloxatone (MD-370503) – monoamine oxidase MAO-A reversible inhibitor
* BMS-181101 (BMY-42569) – serotonin reuptake inhibitor and serotonin 5-HT$_{1A}$ and 5-HT$_{1D}$ receptor agonist
* Buspirone (transdermal; BuSpar Patch) – serotonin 5-HT$_{1A}$ receptor partial agonist
* Casopitant (GW-679769; GW679769) – neurokinin NK$_1$ receptor antagonist
* Centpropazine – unknown mechanism of action
* Cibinetide (ARA-290) – erythropoietin receptor (EpoR) agonist
* Citalopram (controlled-release) – serotonin reuptake inhibitor
* Clavulanic acid (RX-10100; Serdaxin; Zoraxel) – β-lactamase inhibitor and unknown mechanism of action (glutamate transporter GLT1 expression enhancer, dopamine, glutamate, and serotonin modulator, possibly via Munc18-1 and Rab4 interactions)
* Clovoxamine (DU-23811) – serotonin and norepinephrine reuptake inhibitor
* Coluracetam (BCI-540; MKC-231) – ionotropic glutamate AMPA receptor positive allosteric modulator, choline uptake and acetylcholine synthesis enhancer, and racetam
* CP-316311 – corticotropin releasing hormone (CRH) inhibitor
* Crinecerfont (NBI-74788; SSR-125543; SSR-125543A) – corticotropin releasing factor receptor 1 (CRF$_1$) antagonist
* CRL-41789 – undefined mechanism of action
* Cutamesine (AGY-94806; Msc-1; SA-4503) – sigma σ$_1$ receptor agonist
* CX157 (KP157; TriRima; Tyrima) – monoamine oxidase MAO-A reversible inhibitor
* Dapoxetine (LY-210448; Priligy) – serotonin reuptake inhibitor
* Dasotraline (DSP-225289; SEP-225289; SEP-0225289; SEP-289) – serotonin, norepinephrine, and dopamine reuptake inhibitor
* DDP-225 – norepinephrine reuptake inhibitor and serotonin 5-HT$_3$ receptor antagonist
* Decoglurant – metabotropic glutamate mGlu$_2$ and mGlu$_3$ receptor antagonist
* Delequamine (RS-15385; RS-15385197) – α$_2$-adrenergic receptor antagonist
* Delucemine (NPS-1506) – ionotropic glutamate NMDA receptor polyamine site antagonist and serotonin reuptake inhibitor
* Dexmecamylamine (AT-5214; NIH-11008; S-mecamylamine; TC-5214) – α$_3$β$_4$ and α$_4$β$_2$ nicotinic acetylcholine receptor negative allosteric modulator
* Dexnafenodone (LU-43706) – serotonin and norepinephrine reuptake inhibitor
* DMP-695 – corticotropin releasing hormone (CRH) inhibitor
* DOV-216303 – serotonin, norepinephrine, and dopamine reuptake inhibitor
* DPC-368 – undefined mechanism of action
* DSP-1200 – serotonin 5-HT$_{2A}$ receptor antagonist, dopamine D$_2$ receptor antagonist, and α$_{2A}$-adrenergic receptor antagonist
* Edivoxetine (EDP-125; LY-2216684) – norepinephrine reuptake inhbitor
* Elzasonan (CP-448187) – serotonin 5-HT$_{1B}$ and 5-HT$_{1D}$ receptor antagonist
* Emapunil (AC-5216; XBD-173) – translocator protein (TSPO; peripheral benzodiazepine receptor) agonist (neurosteroidogenesis stimulant)
* Emicerfont (GW-876008; GW-876008X) – corticotropin releasing factor receptor 1 (CRF$_1$) antagonist
* Eplivanserin (Ciltyri; Sliwens; SR-46349; SR-46349B; SR-46615A) – serotonin 5-HT$_{2A}$ receptor antagonist
* Eptapirone (F-11440) – serotonin 5-HT$_{1A}$ receptor full agonist
* Esreboxetine ((S,S)-Reboxetine; AXS-14; PNU-165442G) – norepinephrine reuptake inhibitor
* Esuprone (LU-43839) – monoamine oxidase MAO-A reversible inhibitor
* Ethyl eicosapentaenoic acid (Ethyl-EPA) – omega-3 fatty acid
* Farampator (CX-691; ORG-24448) – ionotropic glutamate AMPA receptor positive allosteric modulator
* Fasoracetam (AEVI-001; LAM-105; MDGN-001; NFC-1; NS-105) – unknown mechanism of action (metabotropic glutamate receptor modulator) and racetam
* FCE-25876 – serotonin reuptake inhibitor
* Flerobuterol (CRL-40827) – β-adrenergic receptor agonist
* Flesinoxan (DU-29373) – serotonin 5-HT$_{1A}$ receptor agonist
* Flibanserin (Addyi; BIMT-17; Girosa) – serotonin 5-HT$_{1A}$ receptor agonist, serotonin 5-HT$_{2A}$, 5-HT$_{2B}$, and 5-HT$_{2C}$ receptor antagonist, and dopamine D$_4$ receptor antagonist
* (R)-Fluoxetine – serotonin reuptake inhibitor
* Fluparoxan (GR-50360; GR-50360A) – α$_2$-adrenergic receptor antagonist
* Gaboxadol (LU-02030; LU-2-030; MK-0928; OV-101; THIP) – GABA$_A$ receptor agonist
* Girisopam (EGIS-5810; GYKI-51189) – GABA$_A$ receptor positive allosteric modulator and benzodiazepine
* GYKI-52895 – dopamine reuptake inhibitor
* Haloperidol (CLR-3001) – typical antipsychotic (non-selective monoamine receptor modulator; low-dose withdrawal therapy)
* HT-2157 (SNAP-37889) – galanin GAL$_3$ receptor antagonist
* ICI-170809 (ZM-170809) – serotonin 5-HT$_2$ receptor antagonist
* Idazoxan – α$_2$-adrenergic receptor antagonist
* Ipsapirone (BAY-Q-7821; TVX-Q-7821) – serotonin 5-HT$_{1A}$ receptor partial agonist
* IRFI-165 – adenosine A$_1$ receptor antagonist
* Istradefylline (KW-6002; Nourianz; Nouriast) – adenosine A$_2$ receptor antagonist
* JNJ-18038683 – serotonin 5-HT$_7$ receptor antagonist
* JNJ-19567470 (CRA-5626; R-317573) – corticotropin releasing factor receptor 1 (CRF$_1$) antagonist
* JNJ-26489112 – unknown mechanism of action (topiramate successor)
* JNJ-39393406 – α$_7$ nicotinic acetylcholine receptor positive allosteric modulator
* Lanicemine (AZD-6765) – low-trapping ionotropic glutamate NMDA receptor antagonist
* LB-100 (LB-1) – protein phosphatase 2A (PP2A) inhibitor
* Levoprotiline (CGP-12103; CGP-12103A; CGS-12103; R(–)-oxaprotiline; R(–)-hydroxymaprotiline) – histamine H$_1$ receptor antagonist, other actions, and tetracyclic antidepressant
* Lithium – unknown mechanism of action and mood stabilizer
* Litoxetine (IXA-001; SL-810385) – serotonin reuptake inhibitor and weak serotonin 5-HT$_3$ receptor antagonist
* Losmapimod (FTX-1821; GS-856553; GSK-856553; GW-856553; GW-856553X) – p38-α/β mitogen-activated protein kinase (MAPK) inhibitor and double homeobox 4 (DUX4) inhibitor
* LU-AA34893 (LU-AA-34893) – serotonin receptor modulator
* LU-AA39959 (LU-AA-39959) – ion channel modulator
* Lubazodone (SM-50C; YM-35992; YM-992) – serotonin reuptake inhibitor and serotonin 5-HT$_{2A}$ receptor antagonist
* Masitinib (AB-07105; AB-1010; Alsitek; Masican; Masipro; Masiviera) – tyrosine kinase inhibitor and other actions
* Mecamylamine (Inversine; Tridmac) – nicotinic acetylcholine receptor negative allosteric modulator
* MIN-117 (WF-516) – serotonin and dopamine reuptake inhibitor, serotonin 5-HT$_{1A}$ and 5-HT$_7$ receptor antagonist, and α$_1$-adrenergic receptor antagonist
* MK-1942 – undefined mechanism of action
* ML-105 – undefined mechanism of action
* Naloxone/tianeptine (TNX-601; TNX-601-CR; TNX-601-ER) – weak and atypical μ- and δ-opioid receptor agonist, other actions, tricyclic antidepressant, and μ-opioid receptor antagonist combination
* Naluzotan (PRX-00023) – serotonin 5-HT$_{1A}$ receptor partial agonist and sigma σ$_1$ receptor antagonist
* NB-415 – vasopressin V$_{1b}$ receptor antagonist
* Neboglamine (nebostinel; CR-2249; XY-2401) – ionotropic glutamate NMDA receptor glycine site positive allosteric modulator
* Nefiracetam (BRN 6848330; CCRIS 6729; DM 9384; DMPPA; DN-9384; DZL-221; HL-0812; HPI-001; Motiva; Translon) – unknown mechanism of action (voltage-gated calcium channel potentiator, α$_4$β$_2$ nicotinic acetylcholine receptor potentiator, ionotropic glutamate NMDA receptor potentiator (possible glycine site partial positive allosteric modulator), ionotropic glutamate AMPA receptor potentiator, and GABA$_A$ receptor agonist) and racetam
* Nemifitide (INN-00835) – unknown mechanism of action
* NS-2359 (GSK-372475) – serotonin, norepinephrine, and dopamine reuptake inhibitor
* NS-2389 (GW-650250; GW-650250A) – serotonin, norepinephrine, and dopamine reuptake inhibitor
* ORM-10921 – α$_{2C}$-adrenergic receptor antagonist
* Orvepitant (GW-823296; GW-823296X; GW823296) – neurokinin NK$_1$ receptor antagonist
* Osanetant (ACER-801; SR-142801; SR-142806) – neurokinin NK$_3$ receptor antagonist
* Pexacerfont (BMS-562086) – corticotropin releasing factor receptor 1 (CRF$_1$) antagonist
* PF-04455242 – κ-opioid receptor antagonist
* PT-150 (ORG-34517; SCH-900636) – glucocorticoid receptor antagonist and androgen receptor antagonist
* Radafaxine (GW-353162; (2S,3S)-hydroxybupropion) – norepinephrine and dopamine reuptake inhibitor
* Ramelteon (Rozerem; TAK-375) – melatonin MT$_1$ and MT$_2$ receptor agonist
* Rapastinel (BV-102; GLYX-13; TPPT-amide) – ionotropic glutamate NMDA receptor glycine site partial agonist
* RG-7166 – serotonin, norepinephrine, and dopamine reuptake inhibitor
* Ritanserin (R-55667) – serotonin 5-HT$_{2A}$ and 5-HT$_{2C}$ receptor antagonist
* Robalzotan (AZD-7371; NAD-299) – serotonin 5-HT$_{1A}$ receptor antagonist
* Rolipram (ME-3167; ZK-62711) – phosphodiesterase 4 (PDE4) inhibitor
* Sabcomeline (BCI-224; CEB-242; Memric; SB-202026) – muscarinic acetylcholine M$_1$ receptor agonist
* Saredutant (SR-48968) – neurokinin NK$_2$ receptor antagonist
* SB-236057 – serotonin 5-HT$_{1B}$ receptor inverse agonist
* SB-245570 – serotonin 5-HT$_{1B}$ receptor antagonist
* Sibutramine (Aoquqing; BTS-54524; Ectiva; KES-524; Meridia; Reductase; Reductil; Reduxade; Sibutral) – serotonin, norepinephrine, and dopamine reuptake inhibitor
* Siramesine (LU-28179) – sigma σ$_2$ receptor agonist
* Sirukumab (CNTO-136; Plivensia) – interleukin 6 (IL-6) inhibitor
* SKL-10406 (SKL-DEP) – serotonin, norepinephrine, and dopamine reuptake inhibitor
* SKL-PSY (FZ-016) – serotonin 5-HT$_{1A}$ receptor agonist
* Sodium phenylbutyrate (slow-release; LU-901; Lunaphen) – histone deacetylase (HDAC) inhibitor
* SSR-149415 (SR-149415) – vasopressin V$_{1b}$ receptor antagonist
* SSR-241586 – neurokinin NK$_2$ and NK$_3$ receptor antagonist
* Tandospirone (metanopirone; Sediel; SM-3997) – serotonin 5-HT$_{1A}$ receptor partial agonist and α$_2$-adrenergic receptor antagonist
* Tasimelteon (BMS-214778; Hetlioz; VEC-162) – melatonin MT$_1$ and MT$_2$ receptor agonist
* Tedatioxetine (LU-AA24530) – serotonin, norepinephrine, and dopamine reuptake inhibitor, serotonin 5-HT$_{2A}$, 5-HT$_{2C}$, and 5-HT$_3$ receptor antagonist, and α$_{1A}$-adrenergic receptor antagonist
* Tianeptine (JNJ-39823277; TPI-1062) – weak and atypical μ- and δ-opioid receptor agonist, other actions, and tricyclic antidepressant
* TS-111 – undefined mechanism of action
* Tulrampator (CX-1632; S-47445) – ionotropic glutamate AMPA receptor positive allosteric modulator
* Vanoxerine (boxeprazine; GBR-12909) – atypical dopamine reuptake inhibitor
* Verucerfont (GSK-561679; NBI-77860) – corticotropin releasing factor receptor 1 (CRF$_1$) antagonist
* Vestipitant (GW-597599; GW-597599B) – neurokinin NK$_1$ receptor antagonist
* Viloxazine (Qelbree) – norepinephrine reuptake inhibitor
* VN-2222 – serotonin reuptake inhibitor and serotonin 5-HT$_{1A}$ receptor partial agonist
* VUFB-17649 – serotonin reuptake inhibitor
* VUFB-18285 – serotonin reuptake inhibitor
* ZD-4974 – neurokinin NK$_1$ receptor antagonist
* Zelatriazin (TAK-041; NBI-1065846; NBI-846) – G protein-coupled receptor 139 (GPR139) agonist
* Ziprasidone (Geodon) – atypical antipsychotic (non-selective monoamine receptor modulator)

### Preregistration submission withdrawal

* Aripiprazole/sertraline (ASC-01) – atypical antipsychotic (non-selective monoamine receptor modulator) and serotonin reuptake inhibitor combination

### Formal development never or not yet started

* Mevidalen (LY-3154207; D1 PAM) – dopamine D$_1$ receptor positive allosteric modulator – under development for Lewy body disease
* Nitrous oxide (N$_2$O; "laughing gas") – ionotropic glutamate NMDA receptor antagonist – being studied for depression but doesn't seem to be being formally developed towards approval

## Clinically used drugs
### Approved drugs

* Agomelatine (Valdoxan) – serotonin 5-HT$_{2C}$ receptor antagonist and melatonin MT$_1$ and MT$_2$ receptor agonist
* Amineptine (Survector, Maneon) – norepinephrine and dopamine reuptake inhibitor – withdrawn
* Amisulpride (Solian) – atypical antipsychotic (dopamine D$_2$ and D$_3$ receptor antagonist and serotonin 5-HT$_{2B}$ and 5-HT$_7$ receptor antagonist)
* Amitriptyline (Elavil) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Amoxapine (Asendin) – tetracyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Aripiprazole (Abilify) – atypical antipsychotic (non-selective monoamine receptor modulator)
* Brexanolone (allopregnanolone; SAGE-547; SGE-102; Zulresso) – GABA$_A$ receptor positive allosteric modulator and neurosteroid – approved for postpartum depression
* Brexpiprazole (Rexulti) – atypical antipsychotic (non-selective monoamine receptor modulator)
* Bupropion (Wellbutrin) – norepinephrine and dopamine reuptake inhibitor and nicotinic acetylcholine receptor negative allosteric modulator
* Bupropion/dextromethorphan (Auvelity) – sigma σ$_1$ receptor agonist, serotonin reuptake inhibitor, norepinephrine and dopamine reuptake inhibitor, nicotinic acetylcholine receptor negative allosteric modulator, ionotropic glutamate NMDA receptor antagonist, other actions, and CYP2D6 inhibitor combination
* Butriptyline (Evadyne) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator) – discontinued
* Cariprazine (Vraylar) – atypical antipsychotic (non-selective monoamine receptor modulator)
* Citalopram (Celexa) – serotonin reuptake inhibitor
* Desipramine (Norpramin) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Desvenlafaxine (Pristiq) – serotonin and norepinephrine reuptake inhibitor
* Desvenlafaxine (extended-release; Khedezla) – serotonin and norepinephrine reuptake inhibitor – withdrawn
* Desvenlafaxine (extended-release; WIP-DF17) – serotonin and norepinephrine reuptake inhibitor – registered in South Korea
* Dosulepin (dothiepin; Prothiaden) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Doxepin (Sinequan) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Duloxetine (Cymbalta; Drizalma Sprinkle) – serotonin and norepinephrine reuptake inhibitor
* Escitalopram (Lexapro) – serotonin reuptake inhibitor
* Esketamine (Spravato) – ionotropic glutamate NMDA receptor antagonist
* Fluoxetine (Prozac; Sarafem) – serotonin reuptake inhibitor
* Fluvoxamine (Luvox) – serotonin reuptake inhibitor
* Gepirone (Exxua) – serotonin 5-HT$_{1A}$ receptor partial agonist and α$_2$-adrenergic receptor antagonist
* Hypericum extract (LI-160; St John's wort) – undefined mechanism of action
* Imipramine (Tofranil) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Iproniazid (Marsilid) – monoamine oxidase MAO-A and MAO-B irreversible inhibitor – withdrawn
* Isocarboxazid (Marplan) – monoamine oxidase MAO-A and MAO-B irreversible inhibitor
* Levomilnacipran (Fetzima) – serotonin and norepinephrine reuptake inhibitor
* Levosulpiride (L-sulpiride; Levobren; Levopraid; Levosulpride; RV-12309; Sulpepta) – dopamine D$_2$ and D$_3$ receptor antagonist and serotonin 5-HT$_4$ receptor agonist
* Lofepramine (Lomont) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Lumateperone (Caplyta) – atypical antipsychotic (non-selective monoamine receptor modulator)
* Lurasidone (Latuda) – atypical antipsychotic (non-selective monoamine receptor modulator)
* Maprotiline (Ludiomil) – tetracyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Mianserin (Tolvon) – tetracyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Milnacipran (Dalcipran; Ixel; Savella) – serotonin and norepinephrine reuptake inhibitor
* Mirtazapine (Remeron) – α$_2$-adrenergic receptor antagonist, serotonin 5-HT$_{2A}$, 5-HT$_{2C}$, and 5-HT$_3$ receptor antagonist, histamine H$_1$ receptor inverse agonist, and tetracyclic antidepressant
* Moclobemide (Aurorix; Manerix) – monoamine oxidase MAO-A reversible inhibitor
* Nefazodone (BMY-13754; Dutonin; MJ-13754; MS-13754; Nefadar; Serzone) – serotonin 5-HT$_{1A}$ receptor ligand, serotonin 5-HT$_{2A}$ and 5-HT$_{2C}$ receptor antagonist, α$_1$- and α$_2$-adrenergic receptor antagonist, weak serotonin, norepinephrine, and dopamine reuptake inhibitor, and other actions – mostly withdrawn
* Nomifensine (Merital; Alival) – norepinephrine and dopamine reuptake inhibitor – withdrawn
* Nortriptyline (Aventyl) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Olanzapine (Zyprexa) – atypical antipsychotic (non-selective monoamine receptor modulator)
* Olanzapine/fluoxetine (OFC; Symbyax; ZypZac) – atypical antipsychotic (non-selective monoamine receptor modulator) and serotonin reuptake inhibitor combination
* Opipramol (Ensidon; G-33040; Insidon; Nisidana) – sigma σ$_1$ and σ$_2$ receptor agonist, serotonin 5-HT$_{2A}$ receptor antagonist, dopamine D$_2$ receptor antagonist, α$_1$-adrenergic receptor antagonist, histamine H$_1$ receptor antagonist, other actions, and tricyclic antidepressant
* Paroxetine (Paxil; Seroxat) – serotonin reuptake inhibitor
* Phenelzine (Nardil) – monoamine oxidase MAO-A and MAO-B irreversible inhibitor
* Protriptyline (Vivactil) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Quetiapine (Seroquel) – atypical antipsychotic (non-selective monoamine receptor modulator)
* Reboxetine (Edronax) – norepinephrine reuptake inhibitor
* Selegiline (Emsam) – monoamine oxidase MAO-B irreversible inhibitor, catecholaminergic activity enhancer, and weak norepineprhine releasing agent (via metabolites)
* Sertraline (Zoloft; Lustral) – serotonin reuptake inhibitor
* Setiptiline (Tecipul; Tesolon) – serotonin receptor antagonist, α$_2$-adrenergic receptor antagonist, norepinephrine reuptake inhibitor, and tetracyclic antidepressant
* Tianeptine (Coaxil; Stablon; Tatinol) – weak and atypical μ- and δ-opioid receptor agonist, other actions, and tricyclic antidepressant
* Toludesvenlafaxine (ansofaxine; 4-methylbenzoate desvenlafaxine; desvenlafaxine prodrug; LPM-570065; LY-03005; Ruoxinlin) – serotonin, norepinephrine, and dopamine reuptake inhibitor
* Tranylcypromine (Parnate) – monoamine oxidase MAO-A and MAO-B irreversible inhibitor
* Trazodone (Oleptro; Trittico) – serotonin 5-HT$_{1A}$ receptor partial agonist, serotonin 5-HT$_{2A}$ and 5-HT$_{2C}$ receptor antagonist, α$_1$- and α$_2$-adrenergic receptor antagonist, weak serotonin reuptake inhibitor, and other actions
* Trimipramine (Surmontil) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
* Venlafaxine (Effexor) – serotonin and norepinephrine reuptake inhibitor
* Vilazodone (Viibryd) – serotonin reuptake inhibitor and serotonin 5-HT$_{1A}$ receptor agonist
* Viloxazine (Vivalan) – norepinephrine reuptake inhibitor
* Vortioxetine (Trintellix) – serotonin reuptake inhibitor, serotonin 5-HT$_{1A}$ and 5-HT$_{1B}$ receptor agonist, and serotonin 5-HT$_{1D}$, 5-HT$_3$, and 5-HT$_7$ receptor antagonist
* Zimelidine (Zelmid) – serotonin reuptake inhibitor – withdrawn
* Zuranolone (BIIB-125; S-812217; SAGE-217; SGE-797; Zurzuvae) – GABA$_A$ receptor positive allosteric modulator and neurosteroid – approved for postpartum depression