Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions
Giacomo Salvadore, Jaskaran Singh
CNS Neuroscience & Therapeutics April 12, 2013 DOI: 10.1111/cns.12103 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Anxiety Depression Ketamine Esketamine |
| Keywords | Antidepressant Mood disorders Mechanism biology Pharmacology Hippocampus |
| Citations | 80 |
| Key findings | Ketamine produces rapid antidepressant effects in treatment-resistant mood disorders, likely through increased AMPA signaling and synaptogenesis, but optimal dosing and biomarkers remain unknown. |
Abstract
Several recent studies have shown that a single intravenous subanesthetic dose of ketamine, a NMDA receptor antagonist, exerts rapid antidepressant effects in patients with treatment refractory mood disorders and reduces suicidal ideation. Those insights have fueled tremendous excitement in the efforts to elucidate the mechanism underlying ketamine's antidepressant properties in animal models of depression, as well as in humans through the use of brain imaging as well as peripheral blood measurements. For example, there is emerging evidence that ketamine's antidepressant properties rely on increasing AMPA signaling and rapidly inducing synaptogenesis. While pilot clinical studies are promising, a number of critical questions still remain unanswered. They relate to the safe and effective use of ketamine in patients with mood disorders regarding the optimal dose range, modality and method of administration for acute and long-term maintenance of effect, and the biomarkers associated with response/nonresponse. In this review article, we first summarize the clinical evidence about the use of ketamine in mood disorders, as well as preclinical and humans studies which investigated the mechanisms of action of ketamine, and predictors of antidepressant response in clinical populations. We then provide a critical overview of the knowledge gaps about the use of ketamine in depression and suggest some future research directions for the investigation of ketamine as a promising tool to develop novel more effective and fast acting antidepressants.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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A single intravenous subanesthetic dose of ketamine exerts rapid antidepressant effects and reduces suicidal ideation, but optimal dosing, administration modality, and biomarkers remain unknown.
Synthesized
Comparable studies
Other narrative reviews on ketamine for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement | |
| KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS | 2016 | Review | |
| Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors | 2018 | Review | |
| Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder Patients with treatment-resistant depressive symptoms as part of major depressive... | 2018 | Narrative review | |
| A New Perspective on the Anti-Suicide Effects With Ketamine Treatment Adults with treatment-resistant mood disorders | 2015 | Review |