Trauma re-experiencing episodes during esketamine treatment in patients with treatment-resistant depression and comorbid PTSD: a retrospective case series
Year: 2026
Type: article
Study design: Observational Study
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.
Authors: 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
Institutions: Centre Hospitalier du Rouvray, GHU Paris psychiatrie & neurosciences, Centre Hospitalier Universitaire d'Angers, Centre Hospitalier Universitaire de Saint-Étienne, Centre National de la Recherche Scientifique, Inserm, Université de Montpellier, Centre Hospitalier Universitaire de Montpellier, Institut de Génomique Fonctionnelle, Centre Hospitalier Universitaire de Grenoble, Sciences, Philosophie, Histoire, methodS in Patient-centered outcomes and HEalth ResEarch, Aix-Marseille Université, Institut Fresnel, Centrale Méditerranée, Institut Pascal, Université Clermont Auvergne, Clermont Auvergne INP, Imaging, Brain, and Neuropsychiatry, Centre Hospitalier Universitaire de Tours, Université Paris Cité, Yale University
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,704
OpenAlex ID: W7147293267