NEUROBIOLOGY OF STRESS, DEPRESSION, AND RAPID ACTING ANTIDEPRESSANTS: REMODELING SYNAPTIC CONNECTIONS
Depression and Anxiety March 10, 2014 DOI: 10.1002/da.22227 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine Serotonin Depression |
| Keywords | Antidepressant Nmda receptor Monoamine neurotransmitter Prefrontal cortex Glutamate receptor Hippocampus Cognition |
| Citations | 213 |
| Key findings | Ketamine rapidly increases synaptic connections in the prefrontal cortex and reverses stress-induced synaptic deficits in rodents, offering a novel approach for rapid-acting antidepressants. |
Abstract
Stress and depression are associated with atrophy and loss of neurons in limbic and cortical brain regions that could contribute to the symptoms of depression. Typical monoamine reuptake inhibitor antidepressants have only modest efficacy and require long-term treatment, and are only weakly effective in blocking or reversing these structural changes caused by stress. Recent findings demonstrate that ketamine, an NMDA receptor antagonist, produces rapid antidepressant actions in difficult to treat depressed patients. In addition, preclinical studies demonstrate that ketamine rapidly increases synaptic connections in the prefrontal cortex by increasing glutamate signaling and activation of pathways that control the synthesis of synaptic proteins. Moreover, ketamine rapidly reverses the synaptic deficits caused by exposure to chronic stress in rodent models. Studies of the signaling mechanisms underlying the actions of ketamine have provided novel approaches and targets for new rapid acting antidepressants with decreased side effects, as well as a better understanding of the neurobiology of stress, depression, and treatment response.
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 |