Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity.
Danielle M. Gerhard, Eric S. Wohleb, Ronald S. Duman
Drug Discovery Today February 6, 2016 DOI: 10.1016/j.drudis.2016.01.016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Depression Ketamine Neuroplasticity |
| Keywords | Animals Humans Scopolamine Glutamic acid Receptors, metabotropic glutamate Receptors, n-methyl-d-aspartate Muscarinic antagonists Antidepressive agents Stress, psychological Neuronal plasticity Gaba-a receptor agonists |
| Key findings | Reviews evidence that rapid-acting agents such as the glutamate NMDA receptor antagonist ketamine reverse behavioral and neuronal deficits of chronic stress and depression, and discusses cellular mechanisms proposed to underlie these rapid antidepressant actions along with newer selective glutamatergic receptor targets suggested to be safer with fewer side effects. |
Abstract
Major depression is a chronic and debilitating illness that effects approximately 1 in 5 people, but currently available treatments are limited by low rates of efficacy, therapeutic time lag, and undesirable side effects. Recent efforts have been directed towards investigating rapid-acting agents that reverse the behavioral and neuronal deficits of chronic stress and depression, notably the glutamate NMDA receptor antagonist ketamine. The cellular mechanisms underlying the rapid antidepressant actions of ketamine and related agents are discussed, as well as novel, selective glutamatergic receptor targets that are safer and have fewer side effects.
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 |
Citations in the library
Cited by 40
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- GABA interneurons are the cellular trigger for ketamine's rapid antidepressant actions. Journal of Clinical Investigation November 19, 2019
- Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Scientific Reports October 9, 2017
- Ketamine Rapidly Enhances Glutamate-Evoked Dendritic Spinogenesis in Medial Prefrontal Cortex Through Dopaminergic Mechanisms. Biological Psychiatry January 8, 2021
- Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression Molecular Brain June 16, 2020
and 35 more in the library
Cites 15
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014
- Pathophysiology of depression and innovative treatments: remodeling glutamatergic synaptic connections Dialogues in Clinical Neuroscience March 31, 2014
and 10 more in the library