Is the antidepressant effect of ketamine separate from its psychotomimetic effect? A review of rodent models.
M C Acero-Castillo, M B M Correia, F V Caixeta, V Motta, M Barros, R S Maior
Neuropharmacology November 1, 2024 DOI: 10.1016/j.neuropharm.2024.110088 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Ketamine Esketamine |
| Keywords | Nmda Schizophrenia Psychopharmacology Mental health research Antidepressants Drug mechanisms |
| Citations | 7 |
| Key findings | Ketamine at subanesthetic doses acts both as a fast-acting antidepressant and as a pharmacological model of schizophrenia, with its dual effects arising from NMDA receptor mechanisms. |
Abstract
Ketamine is an NMDA (N-methyl-d-aspartate) glutamate receptor antagonist, which has a myriad of dose-dependent pharmacological and behavioral effects, including anesthetic, sedative, amnestic, analgesic, and anti-inflammatory properties. Intriguingly, ketamine at subanesthetic doses displays a relevant profile both in mimicking symptoms of schizophrenia and also as the first fast-acting treatment for depression. Here, we present an overview of the state-of-the-art knowledge about ketamine as an antidepressant as well as a pharmacological model of schizophrenia in animal models and human participants. Ketamine's dual effect appears to arise from its mechanism of action involving NMDA receptors, with both immediate and downstream consequences being triggered as a result. Finally, we discuss the feasibility of a unified approach linking the glutamatergic hypothesis of schizophrenia to the promising preclinical and clinical success of ketamine in the treatment of refractory depression.
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 |