Esketamine Nasal Spray: Rapid Relief for TRD and Suicide Prevention-Mechanisms and Pharmacodynamics.
Hui Song, Yang Luo, Lingzhi Fang
Neuropsychiatric Disease and Treatment 2024 DOI: 10.2147/NDT.S486118 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Peer reviewed |
|---|---|
| Intervention | Esketamine nasal spray |
| Topics | Depression Esketamine |
| Keywords | Nmda receptors Trd Clinical benefits Pharmacodynamics Safety and efficacy Depression treatment Antidepressant medication Mental health breakthrough Rapid-acting therapeutics Neuroscience innovation |
| Key findings | Esketamine nasal spray effectively alleviates depressive symptoms and prevents suicidal behavior in treatment-resistant depression patients within hours, with sustained benefits over weeks and a good long-term safety profile. |
Abstract
Esketamine nasal spray has emerged as a promising rapid-relief therapy for treatment-resistant depression (TRD) and suicide prevention. This review examines the chemical structure and pharmacodynamics of esketamine, highlighting its primary action on NMDA receptors and additional effects on AMPA receptors, opioid receptors, monoaminergic receptors, and inflammatory pathways. Despite the synergistic mechanisms contributing to its clinical benefits not being fully understood, future studies are essential to refine our understanding and optimize clinical use. Clinical research indicates that esketamine effectively alleviates depressive symptoms and prevents suicidal behavior in TRD patients, demonstrating good safety and efficacy over extended periods. Specifically, multiple randomized controlled trials have shown that esketamine reduces depressive symptoms within hours and maintains these benefits over several weeks, with a favorable safety profile and minimal side effects observed in long-term use. The approval of esketamine for TRD has significant implications for healthcare practices and policies, offering a new therapeutic option that addresses the urgent needs of patients with severe depression.
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 8
- Patient Experience with Intranasal Esketamine in Treatment-Resistant Depression: Insights from a Multicentric Italian Study (REAL-ESKperience) Journal of Personalized Medicine April 1, 2025
- Mentalization and Emotional-Cognitive Rigidity as predictors of esketamine's effects on Treatment-Resistant Depression: Findings from a prospective observational study. Journal of Affective Disorders September 1, 2025
- Personalizing esketamine treatment in TRD and TRBD: the role of mentalization, cognitive rigidity, psychache, and suicidality. Frontiers in Psychiatry 2025
- Efficacy of Intranasal Esketamine in Treatment-Resistant Depression: A Six-Month Real-World Follow-Up Study of Depressive Symptoms, Hopelessness, and Suicide Risk. Human Psychopharmacology: Clinical and Experimental July 1, 2025
- Profiling intranasal esketamine for adults with major depressive disorder and acute suicidal ideation or behavior: a phenotype-informed drug profile Expert Review of Neurotherapeutics August 18, 2026
and 3 more in the library
Cites 34
- 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 for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- 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
- Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II) The International Journal of Neuropsychopharmacology August 26, 2020
and 29 more in the library