Trauma re-experiencing episodes during esketamine treatment in patients with treatment-resistant depression and comorbid PTSD: a retrospective case series.

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.