Esketamine: new hope for the treatment of treatment-resistant depression? A narrative review.
Mohammed S Salahudeen, Cameron M Wright, Gregory M Peterson
Therapeutic advances in drug safety 2020 DOI: 10.1177/2042098620937899 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Intervention | Intranasal esketamine |
| Topics | Depression Esketamine Ketamine |
| Keywords | Trd Antidepressant Intranasal Treatment resistant depression |
| Key findings | Intranasal esketamine is effective and safe in reducing depressive symptoms and achieving clinical response in patients with treatment-resistant depression. |
Abstract
This narrative review aims to provide an overview of the current literature on the pharmacology, safety, efficacy and tolerability of intranasal esketamine, the S-enantiomer of ketamine, for the treatment of treatment-resistant depression (TRD). A literature search using Medline, Embase, PsycINFO and Cochrane Central was conducted (January 2000 to July 2019). Product information and www.clinicaltrials.gov were also reviewed. The literature search was limited to human studies published in English. Phase I, II, and III studies of intranasal esketamine for TRD were reviewed. About a third of patients with major depressive disorder fail to achieve remission despite treatment with multiple antidepressants. This article examines the trials that led to the approval of esketamine in the United States, as well as other recent studies of esketamine for TRD. The findings from limited phase III trials illustrate that intranasal esketamine is effective and safe in reducing depressive symptoms and achieving clinical response in patients with TRD. The optimum duration and frequency of use are not fully understood. Although the nasal spray is a convenient dosage form, its use in practice may be limited by cost and administrative regulation. While it may prove beneficial to many patients who suffer from TRD, further long-term data are required, along with comparative trials with the R-isomer (arketamine). In the interim, care and monitoring should be exercised in its use in clinical practice.
Comparable studies
Other narrative reviews on esketamine 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 | |
| Long-term safety of ketamine and esketamine in treatment of depression | 2022 | Review | |
| Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. | 2024 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review | |
| The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease | 2022 | Review |
Citations in the library
Cited by 31
- Ketamine: Mechanisms and Relevance to Treatment of Depression. Annual Review of Medicine September 20, 2023
- Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. American Journal of Psychiatry March 1, 2025
- Low Doses of Psilocybin and Ketamine Enhance Motivation and Attention in Poor Performing Rats: Evidence for an Antidepressant Property Frontiers in Pharmacology February 26, 2021
- Ancient Roots of Today's Emerging Renaissance in Psychedelic Medicine. Culture, Medicine, and Psychiatry December 1, 2022
- Glutamatergic receptor and neuroplasticity in depression: Implications for ketamine and rapastinel as the rapid-acting antidepressants. Biochemical and Biophysical Research Communications 2022
and 26 more in the library
Cites 23
- 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
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
and 18 more in the library