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 via OpenAlex
Summary
Esketamine, a novel treatment for depression, works through NMDA receptors and intracellular signaling pathways, moving beyond traditional monoamine-based antidepressants. The article reviews its mechanism of action, clinical adverse effects, contraindications, safe administration protocols, and treatment process. Esketamine offers a rapidly acting option for depression, but its use requires careful management due to potential adverse effects and specific contraindications.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Population | Patients with TRD |
| Keywords | Adverse effect Nasal administration Mechanism biology Protocol science Administration probate law |
| Key finding | 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.