Safety concerns on the abuse potential of esketamine: Multidimensional analysis of a new anti-depressive drug on the market.
Jules Baudot, Thomas Soeiro, Marine Tambon, Nicolas Navarro, Gwenaëlle Veyrac, Salim Mezaache, Joëlle Micallef
Fundamental and Clinical Pharmacology June 2022 DOI: 10.1111/fcp.12745 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Qualitative Peer reviewed |
|---|---|
| Intervention | Esketamine |
| Topics | Esketamine Ketamine |
| Keywords | Addictovigilance Clinical trials Drug abuse Pharmacovigilance Web forums |
| Key findings | The authors argue that esketamine's psychoactive effects underlie both its therapeutic effect and its abuse potential, and that pharmacovigilance and web forum data reveal abuse-related adverse events, substance use disorder signs, and off-label use. They report that only one of three short-term efficacy trials found a significant difference from placebo in treatment-resistant depression, and conclude that strict labeling compliance and close monitoring are needed. |
Abstract
Prominent features of esketamine (e.g., similar mechanism of action as ketamine and target population) require to be vigilant regarding its benefits/risks balance and its risks of abuse in real-life settings. The aim of this study was to review all available pharmacological and clinical data to assess the abuse potential of esketamine shortly after its marketing. This multidimensional study is a quantitative and qualitative analysis of complementary data sources, ranging from preauthorization data (i.e., fundamental pharmacology and clinical trials) to real-life settings data (i.e., pharmacovigilance databases and web forums). According to esketamine pharmacology, its psychoactive effects play a role both in its therapeutic effect and its abuse potential. Only one out of the three short-term efficacy trials found a significant difference between esketamine and placebo in treatment-resistant depression. Beside adverse events that may be sought for abuse purpose (e.g., dissociation, sedation, euphoric mood, hallucination, feeling drunk, and derealization), clinical signs related to substance use disorder (e.g., tolerance, withdrawal syndrome, and drug dependence) and misuse (e.g., off-label use) were also identified in pharmacovigilance databases. Analysis of pharmacovigilance narratives and web forums showed that esketamine psychoactive effects are appreciated by some patients, while they are badly experienced by others. Strict compliance with the market authorization, close monitoring of patients by psychiatrists, and surveillance of any signs of misuse, abuse, or dependence must be part of any treatment course.
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
Cited by 9
- Esketamine in depression: putative biomarkers from clinical research. European Archives of Psychiatry and Clinical Neuroscience July 13, 2024
- Is there a risk of esketamine misuse in clinical practice? Therapeutic advances in drug safety 2025
- Repeated subcutaneous esketamine on treatment-resistant depression: An open-label dose titration study. Journal of Affective Disorders January 15, 2025
- Arketamine: a scoping review of its use in humans. European Archives of Psychiatry and Clinical Neuroscience December 16, 2024
- A real-world pharmacovigilance study of esketamine nasal spray. Medicine September 6, 2024
and 4 more in the library
Cites 14
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- 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
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
and 9 more in the library