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.
Glutamatergics
NMDA receptor modulators
Negative modulator
Ketamine (PMI-100, PMI-150, R-107, SHX-001, SLS-002; TUR-002) – non-competitive NMDA receptor antagonist.[1][1][2][3] (
hydroxynorketamine ((2R,6R)-HNK) – metabolite of ketamine which may be involved in ketamine's antidepressant-like effects in mice[2][3])
Esketamine (Esketamine DPI, Falkieri, PG061) – non-competitive NMDA receptor antagonist – approved for TRD, specifically under development for bipolar depression and "depressive disorders"
[4]
Esmethadone (dextromethadone; REL-1017) – NMDA receptor antagonist open channel blocker[5]
Zuranolone (SAGE-217) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of MDD and postpartum depression[9]
Amisulpride(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[14][15]
Brilaroxazine (RP-5063, RP-5000) – AA – specifically under development for the treatment of MDD[16]
Lumateperone (ITI-007, Caplyta) – AA – specifically under development for the treatment of MDD and bipolar.[17] Has been approved to treat BP 1 and BP 2 disorder under the brand name Caplyta.
[8]
Lurasidone (Latuda) – AA – specifically under development for the treatment of MDD
[9]
Pimavanserin (Nuplazid; ACP-103; BVF-048) – 5-HT2A receptor antagonist – specifically under development for the treatment of MDD[18]
Cycloserine/lurasidone (NRX-101; Cyclurad) – NMDA receptor glycine site partial agonist and AA combination – specifically under development for the treatment of bipolar depression[44]
Deudextromethorphan/quinidine (AVP-786, CTP-786) – σ1 receptor agonist, SRI, uncompetitive NMDA receptor antagonist, and other actions[45]
Not under development
The following notable drugs are of investigational interest as potential antidepressants but are not formally under clinical development for approval at this time:
^Rosenblat JD, McIntyre RS (February 2018). "Efficacy and tolerability of minocycline for depression: A systematic review and meta-analysis of clinical trials". Journal of Affective Disorders. 227: 219–225.
doi:
10.1016/j.jad.2017.10.042.
PMID29102836.
^Zeng Y, Wang X, Wang Q, Liu S, Hu X, McClintock SM (November 2013). "Small molecules activating TrkB receptor for treating a variety of CNS disorders". CNS & Neurological Disorders Drug Targets. 12 (7): 1066–77.
doi:
10.2174/18715273113129990089.
PMID23844685.
^Zhang JC, Yao W, Dong C, Yang C, Ren Q, Ma M, Han M, Hashimoto K (December 2015). "Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression". Psychopharmacology. 232 (23): 4325–35.
doi:
10.1007/s00213-015-4062-3.
PMID26337614.
S2CID15076700.
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.
Glutamatergics
NMDA receptor modulators
Negative modulator
Ketamine (PMI-100, PMI-150, R-107, SHX-001, SLS-002; TUR-002) – non-competitive NMDA receptor antagonist.[1][1][2][3] (
hydroxynorketamine ((2R,6R)-HNK) – metabolite of ketamine which may be involved in ketamine's antidepressant-like effects in mice[2][3])
Esketamine (Esketamine DPI, Falkieri, PG061) – non-competitive NMDA receptor antagonist – approved for TRD, specifically under development for bipolar depression and "depressive disorders"
[4]
Esmethadone (dextromethadone; REL-1017) – NMDA receptor antagonist open channel blocker[5]
Zuranolone (SAGE-217) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of MDD and postpartum depression[9]
Amisulpride(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[14][15]
Brilaroxazine (RP-5063, RP-5000) – AA – specifically under development for the treatment of MDD[16]
Lumateperone (ITI-007, Caplyta) – AA – specifically under development for the treatment of MDD and bipolar.[17] Has been approved to treat BP 1 and BP 2 disorder under the brand name Caplyta.
[8]
Lurasidone (Latuda) – AA – specifically under development for the treatment of MDD
[9]
Pimavanserin (Nuplazid; ACP-103; BVF-048) – 5-HT2A receptor antagonist – specifically under development for the treatment of MDD[18]
Cycloserine/lurasidone (NRX-101; Cyclurad) – NMDA receptor glycine site partial agonist and AA combination – specifically under development for the treatment of bipolar depression[44]
Deudextromethorphan/quinidine (AVP-786, CTP-786) – σ1 receptor agonist, SRI, uncompetitive NMDA receptor antagonist, and other actions[45]
Not under development
The following notable drugs are of investigational interest as potential antidepressants but are not formally under clinical development for approval at this time:
^Rosenblat JD, McIntyre RS (February 2018). "Efficacy and tolerability of minocycline for depression: A systematic review and meta-analysis of clinical trials". Journal of Affective Disorders. 227: 219–225.
doi:
10.1016/j.jad.2017.10.042.
PMID29102836.
^Zeng Y, Wang X, Wang Q, Liu S, Hu X, McClintock SM (November 2013). "Small molecules activating TrkB receptor for treating a variety of CNS disorders". CNS & Neurological Disorders Drug Targets. 12 (7): 1066–77.
doi:
10.2174/18715273113129990089.
PMID23844685.
^Zhang JC, Yao W, Dong C, Yang C, Ren Q, Ma M, Han M, Hashimoto K (December 2015). "Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression". Psychopharmacology. 232 (23): 4325–35.
doi:
10.1007/s00213-015-4062-3.
PMID26337614.
S2CID15076700.