Esketamine for treatment‑resistant depression: A review of clinical evidence (Review).
Octavian Vasiliu
Experimental and therapeutic medicine March 2023 DOI: 10.3892/etm.2023.11810 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Intervention | Esketamine |
| Topics | Depression Esketamine Ketamine |
| Keywords | Psychotic depression Tolerability |
| Key findings | The authors conclude that reviewed evidence supports esketamine as an add-on to antidepressants for treatment-resistant depression, but note that a few trials reported no significant effect on depressive symptom severity and that long-term efficacy and safety data are insufficient to guide administration or duration. |
Abstract
Treatment-resistant depression (TRD) is a challenge for psychiatrists, even after more than seven decades since the first antidepressants were used in clinical practice. Non-monoaminergic-based drugs with antidepressant properties have been developed, but to date, only esketamine and brexanolone have been approved for TRD and postpartum depression, respectively. A narrative review on the efficacy and safety of esketamine in the main categories of depressive disorders has been conducted through four electronic databases (Pubmed, Cochrane, EMBASE and Clarivate/Web of Science) The primary objective of the present review was to find evidence that may support the usefulness of esketamine for patients diagnosed with TRD as well as data about its potential adverse effects in the short and long term. A total of 14 papers were reviewed, and their results support the recommendation of esketamine for treatment of TRD as an add-on to antidepressants, but more data is needed in order to assess its long-term efficacy and safety. It must also be mentioned that there have been a few trials which did not report a significant effect on the severity of depressive symptoms with esketamine in TRD, therefore, caution is indicated for patients initiated on this adjuvant agent. There has been insufficient data to formulate specific guidelines about esketamine administration because evidence about favorable or negative prognostic factors of this treatment has been lacking, and the duration of its administration has not been unanimously accepted. Novel directions for research have been identified, especially in the case of patients with TRD and substance use disorders, geriatric or bipolar depression or in major depression with psychotic features.
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 34
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. Biomedicines October 9, 2024
- Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. International Journal of Molecular Sciences December 5, 2024
- Unveiling the Anti-Inflammatory Effects of Antidepressants: A Systematic Review of Human Studies over the Last Decade. Pharmaceuticals June 10, 2025
- Preclinical models of treatment-resistant depression: challenges and perspectives. Pharmacological Reports December 1, 2023
- Exploring Esketamine's Therapeutic Outcomes as an FDA-Designated Breakthrough for Treatment-Resistant Depression and Major Depressive Disorder With Suicidal Intent: A Narrative Review. Cureus February 1, 2024
and 29 more in the library
Cites 22
- 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
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) The International Journal of Neuropsychopharmacology July 9, 2019
- Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study Biological Psychiatry November 4, 2015
and 17 more in the library