Intranasal esketamine use in treatment-resistant depression: mechanism of action, clinical adverse effects, contraindications, safe administration protocol and treatment process
Abdullah Burak Uygur, Kadir Karakuş, Selime Çelik Erden, Rabia Önem, Ali Emre Öz, Ahmet Al, Umut Gölgeli, Şerifhan Mirac Sarı
Academic Journal of Neuropsychiatry and Neuropsychology June 27, 2026 DOI: 10.51271/ajnn-0051 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Patients with TRD |
| Topics | Depression Esketamine |
| Keywords | Adverse effect Nasal administration Mechanism biology Protocol science Administration probate law Pharmacology Intensive care medicine Anesthesia Depression economics Process computing Mechanism of action Bioinformatics Drug administration Psychological intervention Monoamine neurotransmitter |
| Key findings | Esketamine provides a novel therapeutic approach for depression by targeting NMDA receptors and intracellular signaling pathways, with a need for careful administration due to adverse effects and contraindications. |
Abstract
The U.S. Food and Drug Administration (FDA) has increasingly focused on breakthrough molecular mechanisms, rapidly acting medications, and expanded therapeutic indications in the treatment of depression. During this period, psychiatric interventions targeting N-methyl-D-aspartate (NMDA) receptors and intracellular signaling pathways have gained prominence, moving beyond the traditional monoamine (serotonin/norepinephrine) hypothesis. This article reviews the mechanism of action, clinical adverse effects, contraindications, safe administration protocols, and treatment process associated with esketamine, one of these novel therapeutic approaches.
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 |