Trauma re-experiencing episodes during esketamine treatment in patients with treatment-resistant depression and comorbid PTSD: a retrospective case series.
Maud Rothärmel, Lila Mekaoui, François Kazour, Morgane Herrero, Eva-Maria Beetz-Lobono, Aiste Lengvenyte, Jérôme Holtzmann, Philippe Raynaud, Macarena Cuenca, Samuel Bulteau, Pierre De Maricourt, Thomas Husson, Emilie Olié, Bénédicte Gohier, Anne Sauvaget, Raphaël Gaillard, Raphaëlle Richieri, David Szekely, Ludovic Samalin, Olivier Guillin, Virginie Moulier, Wissam El-Hage, Andrew Laurin, Lucie Berkovitch
European Journal of Psychotraumatology April 1, 2026 DOI: 10.1080/20008066.2025.2609425 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective observational study Case report Peer reviewed |
|---|---|
| Sample size | 22 |
| Population | Adult patients with treatment-resistant depression and comorbid post-traumatic stress disorder receiving esketamine nasal spray across 11 psychiatric departments |
| Intervention | Esketamine nasal spray |
| Topics | Depression Esketamine PTSD |
| Keywords | Real-life data Reexperimentación traumática Traumatic re-experiencing |
| Citations | 1 |
| Key findings | Trauma re-experiencing episodes during esketamine treatment resolved in most patients as sessions continued, and favorable clinical outcomes for both depression and PTSD were observed when treatment was maintained. |
Abstract
Background: Posttraumatic stress disorder (PTSD) is a severe and frequent affection that is highly comorbid to major depressive disorder. Comorbid PTSD and depression increase the risk of treatment-resistant depression (TRD), with a high risk of functional impairment and suicide. Esketamine nasal spray is a recent validated treatment for TRD, but its efficacy on comorbid TRD-PTSD remains insufficiently documented. In particular, it is unknown whether traumatic re-experiencing may occur during esketamine treatment and if so, how it influences clinical outcomes.Objectives: Our objective was to describe trauma re-experiencing episodes during esketamine sessions and their impact on clinical trajectories within an ecological sample of patients with comorbid TRD-PTSD.Methods: We retrospectively collected clinical data of patients receiving esketamine nasal spray for TRD for whom at least one trauma re-experiencing episodes had been identified by clinicians during esketamine sessions across 11 psychiatric departments.Results: Between February 2020 and March 2023, 22 adult patients with TRD met inclusion criteria. In sixteen patients (72.7%) trauma re-experiencing episodesdisappeared as the sessions progressed. In six patients (27.3%), esketamine treatment was stopped because of trauma re-experiencing episodes. When esketamine was continued, favourable clinical outcomes were observed both for depression and PTSD (depression response rate: 45.5% and remission rate: 22.7%; PTSD improvement rate: 45.5% and remission: 18.2%).Limitations: The retrospective design of the study and the absence of a comparator group are the main limitations of our study.Conclusions: Our results suggest that esketamine can be safely administered to patients with comorbid PTSD and TRD, and that the occurrence of trauma re-experiencing episodes does not hinder clinical response.
Comparable studies
Other observational and cohort studies on ketamine for PTSD, most cited first.
Citations in the library
Cited by 2
- Toward Integrating Intranasal Esketamine with Traumatic-Memory Psychotherapy in Treatment-Resistant Depression: A Narrative Review and Feasibility-Oriented Protocol Proposal. Behavioral Sciences May 14, 2026
- Psychedelics and suicidality: A double-edged sword - risks, mechanisms, and moving forward. European Neuropsychopharmacology September 19, 2026
Cites 20
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up. Journal of Substance Abuse Treatment December 1, 2002
- A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. American Journal of Psychiatry January 5, 2021
and 15 more in the library