KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS
Chadi G. Abdallah, Thomas G. Adams, Benjamin Kelmendi, Irina Esterlis, Gerard Sanacora, John H. Krystal
Depression and Anxiety April 6, 2016 DOI: 10.1002/da.22501 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Anxiety Ketamine Esketamine |
| Keywords | Mechanism biology Mechanism of action Action physics Antidepressant Psychotherapist Pharmacology |
| Citations | 204 |
| Key findings | A single subanesthetic dose of ketamine produces rapid antidepressant effects in individuals with treatment-resistant depression, likely through a glutamate surge that leads to synaptogenesis and reversal of stress-related changes in the prefrontal cortex. |
Abstract
Major depressive disorder (MDD) is a common and debilitating psychiatric disorder. Traditional antidepressants are of limited efficacy and take weeks to months to yield full therapeutic effects. Thus, there is a clear need for effective rapid-acting antidepressant medications. The N-methyl-d-aspartate receptor (NMDA-R) antagonist, ketamine, has received a great deal of attention over the last 20 years due to the discovery that a single subanesthetic dose leads to a rapid antidepressant effect in individuals with treatment-resistant depression. Animal and human research suggest that ketamine's antidepressant effects are mediated by a glutamate surge that leads to a cascade of events that result in synaptogenesis and reversal of the negative effects of chronic stress and depression, particularly within the prefrontal cortex (PFC). Preclinical and clinical data have provided compelling insights into the mechanisms underlying the rapid-acting antidepressant effects of ketamine. This review discusses stress-related neurobiology of depression and the safety, tolerability, and efficacy of ketamine for MDD, along with a review of ketamine's mechanism of action and prospective predictors of treatment response. Research limitations and future clinical prospects are also discussed.
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 subanesthetic dose of ketamine produces rapid antidepressant effects in treatment-resistant depression, likely via a glutamate surge leading to synaptogenesis.
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 | |
| 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 | |
| Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions | 2013 | Review | |
| A New Perspective on the Anti-Suicide Effects With Ketamine Treatment Adults with treatment-resistant mood disorders | 2015 | Review |