Ketamine for psychotic depression: An overview of the glutamatergic system and ketamine's mechanisms associated with antidepressant and psychotomimetic effects.
Tuyen T. Le, Joshua D. Di Vincenzo, Kayla M Teopiz, Yena Lee, Danielle S. Cha, Leanna M.W. Lui, Nelson B Rodrigues, R. Ho, Bing Cao, Kangguang Lin, Flora Nasri, Hartej Gill, Orly Lipsitz, Mehala Subramaniapillai, Rodrigo B. Mansur, Joshua D. Rosenblat, Roger S McIntyre
Psychiatry Research October 1, 2021 DOI: 10.1016/j.psychres.2021.114231 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Esketamine Ketamine |
| Citations | 26 |
| Key findings | The safety and efficacy of ketamine for psychotic depression are not established, and future trials should include patients with psychotic features. |
Abstract
Approximately 0.35-1% of the general population is afflicted with psychotic depression at some time in their life. Psychotic depression is a subtype of major depressive disorder characterized by mood congruent hallucinations and/or delusions. Patients with psychotic depression often represent the most severe cases, with high relapse and mortality rate. Although treatment guidelines recommend a combination of antidepressants and antipsychotics or electroconvulsive therapy, most patients subsequently relapse due to treatment resistance. Furthermore, with the concern of antipsychotic drug's side effects (e.g., tardive dyskinesia), there is a need for an alternative pharmacotherapy for psychotic depression. Recently, several case studies demonstrated that treatment with ketamine not only ameliorated mood, but also improved psychotic symptoms in patients with treatment-resistant depression and psychotic features. However, the safety of ketamine in these patients is controversial since ketamine is known to induce psychotomimetic and dissociative effects. Additionally, the efficacy and safety of ketamine in patients with psychotic depression has not been established as most clinical trials have excluded these persons due to the theorized risk of aggravating psychotic symptoms. Notwithstanding, it is not established empirically that ketamine treatment in psychotic depression would predictably amplify psychotic symptoms and/or overall illness presentation. Future trials evaluating ketamine in depression should include patients with psychotic features to inform whether ketamine is safe and effective in this subpopulation.
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 14
- The abuse liability of ketamine: A scoping review of preclinical and clinical studies. Journal of Psychiatric Research May 1, 2022
- Ketamine, an Old–New Drug: Uses and Abuses Pharmaceuticals December 21, 2023
- The Montreal model: an integrative biomedical-psychedelic approach to ketamine for severe treatment-resistant depression Frontiers in Psychiatry September 19, 2023
- Ketamine as Add-On Treatment in Psychotic Treatment-Resistant Depression Brain Sciences January 13, 2023
- Expert Opinion on Psychedelic-Assisted Psychotherapy for People with Psychotic Symptoms Research Square January 25, 2022
and 9 more in the library
Cites 41
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
and 36 more in the library