This is a list of investigational antidepressants, or antidepressants that are currently under development for clinical use in the treatment of mood disorders but are not yet approved. Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. All drugs listed are specifically under development for major depressive disorder (MDD) and/or treatment-resistant depression (TRD) unless noted otherwise. Other forms of depression may include bipolar depression and postpartum depression.
Glutamatergics
NMDA receptor modulators
4-Chlorokynurenine (AV-101) – NMDA receptor glycine site antagonist
Apimostinel (GATE-202, NRX-1074) – NMDA receptor modulator
Arketamine (PCN-101, HR-071603) – unknown mechanism of action, indirect AMPA receptor activator
Esketamine (Esketamine DPI, Falkieri, PG061) – non-competitive NMDA receptor antagonist – approved for TRD, specifically under development for bipolar depression and "depressive disorders" Esmethadone (dextromethadone; REL-1017) – NMDA receptor antagonist open channel blocker Ketamine (PMI-100, PMI-150, R-107, SHX-001, SLS-002; TUR-002) – non-competitive NMDA receptor antagonist MIJ-821 – NMDA receptor subunit 2B (NR2B) negative allosteric modulator Rislenemdaz (CERC-301, MK-0657) – NMDA receptor NR2B antagonist Zelquistinel (GATE-251, AGN-241751) – NMDA receptor positive allosteric modulator
AMPA receptor modulators
TAK-653 (NBI-1065845) – AMPA receptor positive allosteric modulator
Monoaminergics
Monoamine reuptake inhibitors
OPC-64005 – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) PDC-1421 (BLI-1005) – norepinephrine reuptake inhibitor (NRI)
Monoamine reuptake inhibitors and receptor modulators
Hypidone (YL-0919) – SRI, 5-HT1A receptor partial agonist, and 5-HT6 receptor agonist
TGBA01AD (FKB01MD) – serotonin reuptake inhibitor (SRI), 5-HT1A and 5-HT1D receptor agonist, and 5-HT2 receptor antagonist Vortioxetine (Trintellix) – SRI, 5-HT1A receptor agonist, 5-HT1B receptor partial agonist, 5-HT1D, 5-HT3, and 5-HT7 receptor antagonist – approved for MDD, under development for bipolar depression
Monoamine releasing agents
Lisdexamfetamine (Elvanse, LDX, NRP-104, S-877489, SHP-489, SPD-489, Tyvense, Venvanse, Vyvanse) – norepinephrine–dopamine releasing agent (NDRA) Midomafetamine (MDMA; ecstasy) – serotonin–norepinephrine–dopamine releasing agent (SNDRA)
Monoamine receptor modulators
Aramisulpride/esamisulpride (85:15 ratio) (SEP-4199) – 5-HT7 receptor antagonist (aramisulpride) and D2 and D3 receptor antagonist (esamisulpride) – specifically under development for the treatment of bipolar depression Gepirone (TGFK07AD; Travivo) – 5-HT1A receptor partial agonist Pramipexole (CTC-501, CTC-413) – D2, D3, and D4 receptor agonist Psilocybin – 5-HT2A receptor agonist
Atypical antipsychotics
Brilaroxazine (RP-5063, RP-5000) – AA – specifically under development for the treatment of MDD Cariprazine (Reagila, Vraylar) – AA – approved for bipolar depression, under development for MDD Lumateperone (ITI-007, Caplyta) – AA – specifically under development for the treatment of MDD and bipolar. Has been approved to treat BP 1 and BP 2 disorder under the brand name Caplyta.
depression
Lurasidone (Latuda) – AA – specifically under development for the treatment of MDD Pimavanserin (Nuplazid; ACP-103; BVF-048) – 5-HT2A receptor antagonist – specifically under development for the treatment of MDD
Others
Ademetionine (SAMe; MSI-190, MSI-195, Strada) – cofactor in monoamine neurotransmitter biosynthesis – specifically under development in the United States and Europe for the adjunctive treatment of MDD
GABAergics and neurosteroids
GABAA receptor positive modulators
Zuranolone (SAGE-217) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of MDD and postpartum depression
Others
3β-Methoxypregnenolone (MAP-4343) – selective microtubule-associated protein 2 (MAP2) stimulant Itruvone (PH-10) – vomeropherine (precise mechanism of action unknown/undisclosed)
Opioidergics
κ-Opioid receptor antagonists
Aticaprant (JNJ-67953964, CERC-501, LY-2456302) – selective κ-opioid receptor antagonist BTRX-335140 (BTRX-140) – selective k-opioid receptor antagonist Buprenorphine/samidorphan (ALKS-5461) – κ-opioid receptor antagonist and μ-opioid receptor antagonist CVL-354 – selective κ-opioid receptor antagonist