The promise of ketamine for treatment-resistant depression: current evidence and future directions
Kaitlin E. DeWilde, Cara F. Levitch, James W. Murrough, Sanjay J. Mathew, Dan V. Iosifescu
Annals of the New York Academy of Sciences February 3, 2015 DOI: 10.1111/nyas.12646 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Depression Esketamine Ketamine |
| Key findings | Argues that the glutamate neurotransmitter system, particularly through the NMDA receptor antagonist ketamine, offers a promising alternative to conventional monoamine-targeting antidepressants for major depressive disorder. Clinical trials indicate ketamine acts rapidly and may affect dimensions of psychopathology including anhedonia, cognition, and suicidality, though safety, administration methods, and misuse risks require consideration. |
Abstract
Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is becoming a significant public health threat. Current treatments for MDD primarily consist of monoamine‐targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant in MDD. We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with the NIMH Research Domain Criteria initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of glutamatergic agents other than ketamine currently being tested as novel antidepressants.
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 16
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review Frontiers in Neuroanatomy March 18, 2022
- Investigational drugs in recent clinical trials for treatment-resistant depression Expert Review of Neurotherapeutics January 16, 2017
- The neurophysiology of ketamine: an integrative review Reviews in the Neurosciences May 5, 2020
- Repurposing potential of ketamine: Opportunities and challenges Indian Journal of Psychological Medicine January 17, 2020
and 11 more in the library
Cites 20
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
and 15 more in the library