Rethinking ketamine and esketamine action: Are they antidepressants with mood-stabilizing properties?
Giacomo d'Andrea, Mauro Pettorruso, Giorgio Di Lorenzo, Gianluca Mancusi, Roger S McIntyre, Giovanni Martinotti
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology May 2023 DOI: 10.1016/j.euroneuro.2023.02.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Interventions | Ketamine Esketamine |
| Topics | Esketamine Ketamine |
| Keywords | Bipolar depression Mood stabilizers Rapid-acting therapies Trd |
| Key points | Argues that ketamine and esketamine may be effective not only as antidepressants in severe treatment-resistant depression but also against mixed features, anxiety, dysphoric mood, and bipolar traits, and proposes that bipolar elements could predict response and that these substances might act as mood stabilizers. Contends that their pharmacodynamic action goes beyond non-competitive NMDA receptor antagonism and calls for further research, particularly on esketamine nasal spray in bipolar depression. |
Abstract
Ketamine and esketamine, the S-enantiomer of the racemic mixture, have recently generated considerable interest as potential therapeutic agents for Treatment-Resistant Depression (TRD), a complex disorder that includes various psychopathological dimensions and distinct clinical profiles (e.g., comorbid personality disorder, bipolar spectrum, dysthymic disorder). This perspective article provides a comprehensive overview of the action of ketamine/esketamine from a dimensional point of view, taking into account the high prevalence of bipolarity in TRD and the evidence of the efficacy of these substances on mixed features, anxiety, dysphoric mood, and, generally, bipolar traits. Additionally, the article underscores the complexity of the pharmacodynamic mechanisms of action of ketamine/esketamine, which goes beyond the non-competitive antagonism of NMDA-R. The need for further research and evidence is highlighted, mainly to evaluate the efficacy of esketamine nasal spray in bipolar depression, the presence of bipolar elements as a predictor of response, and the potential role of these substances as mood stabilizers. The article implies that, in the future, ketamine/esketamine could be used with fewer limitations, not only as antidepressants for the most severe form of depression but also as valuable tools to stabilize subjects with mixed symptoms or bipolar spectrum.
Comparable studies
Other theoretical and historical papers on esketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Adjunctive dopaminergic enhancement of esketamine in treatment-resistant depression. | 2022 | Theoretical or philosophical paper | |
| Esmethadone (REL-1017) and Other Uncompetitive NMDAR Channel Blockers May Improve Mood Disorders via Modulation of Synaptic Kinase-Mediated Signaling. | 2022 | Theoretical or philosophical paper |