List of investigational antidepressants

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) or treatment-resistant depression (TRD) unless noted otherwise.

Glutamatergics

NMDA receptor modulators

Others

Monoaminergics

Monoamine reuptake inhibitors

Monoamine reuptake inhibitors and receptor modulators

Monoamine receptor modulators

Atypical antipsychotics
  • Brilaroxazine (RP-5063, RP-5000) – AA – specifically under development for the treatment of MDD and depressive episodes in bipolar disorder[23]
  • Lumateperone (ITI-007) – AA – specifically under development for the treatment of depressive episodes in bipolar disorder[24]

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[25]

Neurosteroids

GABAA receptor positive modulators
  • Ganaxolone (CCD-1042) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of postpartum depression[26]
  • Zuranolone (SAGE-217) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of both MDD and postpartum depression[27]

Others
  • 3β-Methoxypregnenolone (MAP-4343) – selective microtubule-associated protein 2 (MAP2) stimulant[28]
  • PH-10 – vomeropherine (precise mechanism of action unknown/undisclosed)[29]

Opioidergics

κ-Opioid receptor antagonists

Others

Others

Mixed

Combinations
  • Bupropion/dextromethorphan (AXS-05) – σ1 receptor agonist, SNRI, non-competitive nicotinic acetylcholine receptor antagonist, uncompetitive NMDA receptor antagonist, and other actions[49]
  • Cycloserine/lurasidone (NRX-101; Cyclurad) – NMDA receptor glycine site partial agonist and AA combination – specifically under development for the treatment of depressive episodes in bipolar disorder[50]
  • Dextromethorphan/quinidine (AVP-786/AVP-923) – σ1 receptor agonist, SNRI, uncompetitive NMDA receptor antagonist, and other actions[51]

Not under development

The following drugs are currently of investigational interest as potential antidepressants but are not formally under clinical development for approval at this time:

See also

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