Clinical pharmacological innovation in the treatment of depression.
Jeffrey M. Witkin, Lalit K Golani, Jodi L Smith
Expert Review of Clinical Pharmacology April 1, 2023 DOI: 10.1080/17512433.2023.2198703 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Scoping review Peer reviewed |
|---|---|
| Topics | Depression Ketamine |
| Keywords | Antidepressant Nmda receptors Psychedelics |
| Citations | 18 |
| Key findings | Rapid-acting antidepressants with efficacy in treatment-resistant patients have emerged, many based on glutamatergic mechanisms and the model of ketamine, but gaps remain in patient-treatment matching and prevention of MDD. |
Abstract
Deficiencies in standard of care antidepressants are driving novel drug discovery. A new age of antidepressant medications has emerged with the introduction of rapid-acting antidepressants with efficacy in treatment-resistant patients. The newly approved medicines and those in clinical development for major depressive disorder (MDD) are documented in this scoping review of newly approved and emerging antidepressants. Compounds are evaluated for clinical efficacy, tolerability, and safety and compared to those of standard of care medicines. A new age of antidepressant discovery relies heavily on glutamatergic mechanisms. New medicines based upon the model of ketamine have been delivered and are in clinical development. Rapid onset and the ability to impact treatment-resistant depression, raises the question of the best first-line medicines for patients. Drugs with improvements in tolerability are being investigated (e.g. mGlu2/3 receptor antagonists, AMPA receptor potentiators, and novel NMDA receptor modulators). Multiple companies are working toward the identification of novel psychedelic drugs where the requirement for psychedelic activity is not fully known. Gaps still exist - methods for matching patients with specific medicines are needed, and medicines for the prevention of MDD and its disease progression need research attention.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |
Citations in the library
Cited by 5
- (R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders. International Journal of Molecular Sciences June 20, 2024
- Advances in the study of NMDA receptors in depression pathogenesis and the antidepressant efficacy of their antagonists. Asian Journal of Psychiatry June 1, 2025
- Safety in treatment: Classical pharmacotherapeutics and new avenues for addressing maternal depression and anxiety during pregnancy. Pharmacological Reviews May 1, 2025
- Ketamine - An Imperfect Wonder Drug? Biochemical Pharmacology November 1, 2024
- Effect of Single Intravenous Injection of Esketamine on Postpartum Depression after Labor Analgesia and Potential Mechanisms: A Randomized, Double-blinded Controlled Trial Research Square June 30, 2023
Cites 46
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
and 41 more in the library