Editorial: Retuning the Adolescent Brain: Esketamine and Rapid Structural Change in the rACC.
Yunjia Liu, Qiang Wang
Journal of the American Academy of Child & Adolescent Psychiatry March 17, 2026 DOI: 10.1016/j.jaac.2026.03.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Adolescents with major depressive disorder |
| Topics | Esketamine |
| Key findings | Esketamine may produce faster symptom relief than conventional antidepressants in adolescent depression, but its neural mechanisms in the developing brain remain incompletely understood. |
Abstract
Adolescent major depressive disorder (MDD) is a leading cause of disability worldwide and a major, modifiable risk factor for suicide, which remains the second leading cause of death in this age group.1 For 30% to 50% of patients who fail to achieve remission despite multiple treatment steps, the clinical and psychosocial consequences are substantial.2 Although selective serotonin-reuptake inhibitors are widely used as first-line treatments, their therapeutic effects typically require several weeks to emerge, and a substantial proportion of adolescents do not respond to an initial antidepressant trial. Together, the delayed efficacy and incomplete response contribute to a critical treatment gap during which vulnerable youth remain at elevated risk. These limitations have driven growing interest in rapid-acting interventions such as the N-methyl-D-aspartate (NMDA) receptor antagonist esketamine. Multiple pieces of evidence suggest that esketamine can produce faster symptom relief than conventional antidepressants,2 including efficacy as a monotherapy in treatment-resistant depression3; however, its neural mechanisms remain incompletely understood. A clearer understanding of how esketamine acts on the developing brain is necessary to guide clinical use and to inform more targeted prevention strategies.
Comparable studies
Other narrative reviews on esketamine, 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 | |
| The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence. | 2023 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review |
Citations in the library
Cites 3
- Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry July 2, 2025
- Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes. Translational Psychiatry October 31, 2025
- Transcriptional Signatures of Mitochondrial Metabolism Predict Esketamine-Induced rACC Structural Changes in Adolescent Major Depression. Journal of the American Academy of Child & Adolescent Psychiatry December 31, 2025