Adverse drug events and toxicological mechanisms of esketamine: a study based on US Food and Drug Administration Adverse Event Reporting System and network toxicology analysis.
Lu Wang, Rui Xiong, Hengxu Liu, Shipeng Zhang, Ling Xu, Xiaodan Lai
Naunyn-Schmiedeberg's Archives of Pharmacology February 26, 2026 DOI: 10.1007/s00210-026-05108-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational pharmacovigilance study Peer reviewed |
|---|---|
| Sample size | 7,804 |
| Population | Individuals with esketamine-related adverse drug event reports in the FDA Adverse Event Reporting System (FAERS), analyzed by age subgroup |
| Intervention | Esketamine |
| Duration | Case reports from the first quarter of 2019 through the second quarter of 2024; most adverse events reported within 30 days of treatment start |
| Topics | Esketamine |
| Keywords | Humans Antidepressive agents Age factors Adolescent Child, preschool Infant United states Female Pharmacovigilance Network toxicology |
| Citations | 1 |
| Key findings | Esketamine-related adverse drug event reporting differed by age, with three age subgroups identified and eight general preferred-term signals shared across all subgroups. Most events were reported within 30 days of treatment start, and time-to-onset tended to lengthen with increasing age. Network toxicology suggested potential mechanisms involving calcium signaling, lipid and atherosclerosis, and PI3K/Akt signaling pathways. |
Abstract
Esketamine is a novel antidepressant approved by the US Food and Drug Administration (FDA) in 2019, but comprehensive studies on the post-marketing safety evaluation of esketamine across age groups remain limited. The objective of this study is to provide the age-based pharmacovigilance profile of esketamine and the potential toxicological mechanisms, which may provide insights to inform the development of rational and personalized drug use. In our study, age-related differences in adverse drug event (ADE) reporting were explored through data mining of the FDA Adverse Event Reporting System (FAERS), and the potential mechanism of esketamine-related ADE was explored through network toxicology analysis. A total of 7804 cases are extracted between the first quarter of 2019 and the second quarter of 2024. The disproportionality analysis determined 8754 ADEs involving 223 preferred terms (PTs) and 19 system organ classes (SOCs) overall. Three subgroups are identified by the age of ADEs occurrence. Eight general PT signals were identified across all subgroups. Some important age-specific ADEs are highlighted and analyzed. The time-to-onset analysis reveals that most of the ADEs are reported within 30 days from the start of treatment. And the time exhibits a trend of prolongation as age increases. The potential underlying mechanisms of ADEs of esketamine may involve multiple and complex signaling pathways, such as the calcium signaling pathway, lipid and atherosclerosis, and the PI3K/Akt signaling pathway. The results indicate differential reporting of esketamine-related ADEs based on age. Accordingly, the hypothesis-generating suggestions for implementing the personalized ADE monitoring and health care based on age in esketamine treatment are discussed.
Comparable studies
Other observational and cohort studies on esketamine, most cited first.
Citations in the library
Cites 10
- 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 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
- 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
- Novel rapid treatment options for adolescent depression. Pharmacological Research March 1, 2024
and 5 more in the library