![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
ABSTRACT
Introduction
Major depressive disorder (MDD) continues to be one of the highest contributors to disease burden and years lived with disability in the world. Current existing treatments have been associated with intolerable side effects, long onset of action and suboptimal remission rates. Newer agents are being developed that will be reviewed here, such as glutamate and gamma-aminobutyric acid (GABA) and the reinvigorated testing of psychedelic drugs. This review will summarize the target mechanisms of the newer ADTs currently in development and available on the market.
Areas covered
It briefly covers the existing agents for MDD and treatment-resistant depression (TRD) and the need for new agents with higher efficacy. Therapeutic agents currently in Phase II or later clinical trials are listed and discussed, based on a thorough review of the US National Institutes of Health clinicaltrials.gov index and a search of the Informa Pharmaprojects database. Compounds of interest are grouped into scientific rationale and include atypical antipsychotics, GABA positive allosteric modulators, glutamatergic agents, opioids, orexin 2 receptor antagonists, and psychedelics.
Expert Opinion
New therapeutic agents currently in development are promising, with a more rapid onset of action and the ability to augment and treat TRD.
List of Abbreviations
| 5-MeO-DMT | = | 5-methoxy-N,N-dimethyltryptamine |
| ACTH | = | adrenocorticotropic hormone |
| ADT | = | antidepressant treatment |
| AMPA | = | α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid |
| GABA | = | gamma-aminobutyric acid |
| Glu | = | Glutamate |
| HAMD-17 | = | Hamilton Depression Rating Scale |
| IR | = | immediate release |
| KOR | = | kappa opioid receptor |
| LSD | = | lysergic acid diethylamide |
| MADRS | = | Montgomery-Asberg Depression Rating Scale |
| MAOI | = | monoamine oxidase inhibitors |
| MDD | = | major depressive disorder |
| NAM | = | negative allosteric modulator |
| NET | = | norepinephrine transporter |
| NMDA | = | N-methyl-d-aspartate |
| NMDAR | = | N-methyl-D-aspartate receptor |
| OX2R | = | orexin 2 antagonist |
| NET | = | norepinephrine transporter |
| PAM | = | positive allosteric modulators |
| TCA | = | tricyclic antidepressants |
| TRD | = | treatment-resistant depression |
| SNRI | = | serotonin norepinephrine reuptake inhibitors |
| SSRI | = | prescribed selective serotonin reuptake inhibitors |
| TRD | = | treatment-resistant depression |
Disclosure statement
The authors report there are no competing interests to declare.