Esketamine-induced post-traumatic stress disorder flashbacks during treatment-resistant depression indication: is it just a side effect?

BackgroundPosttraumatic stress disorder (PTSD) is a severe and frequent affection that is highly comorbid to major depressive disorder. Comorbid PTSD and depression are usually treatment-resistant, with a high risk of functional impairment and suicide. Esketamine nasal spray is a recent validated treatment for treatment-resistant depression (TRD), but its efficacy on comorbid TRD-PTSD remains insufficiently documented. In particular, flashbacks can occur during esketamine administration and their influence on clinical outcomes is unknown. ObjectivesOur main objective was to describe esketamine-induced traumatic flashbacks and their impact on clinical trajectories within a sample of patients with comorbid TRD-PTSD. MethodsWe retrospectively collected clinical data of patients receiving esketamine nasal spray for TRD with comorbid PTSD who experienced at least one flashback of their trauma during esketamine sessions across 11 psychiatric departments. ResultsBetween February 2020 and March 2023, 22 adult patients with TRD met inclusion criteria. In sixteen patients (72.7%) flashbacks disappeared as the sessions progressed. In six patients (27.3%), esketamine treatment was stopped because of persistent flashbacks. When esketamine was continued, clinical response was observed both for depression and PTSD (depression response rate: 45.5% and remission rate: 22.7%; PTSD response rate: 45.5% and remission: 18.2%). LimitationsThe retrospective design of the study and the absence of a comparator group are the main limitations of our study. ConclusionsOur results suggest that the occurrence of esketamine-induced traumatic flashbacks does not hinder clinical response. On the contrary, when managed appropriately and combined with targeted psychotherapy, it could even contribute to positive outcomes. HighlightsO_LIEsketamine nasal spray is recently validated for treatment-resistant depression C_LIO_LIIts efficacy on comorbid post-traumatic stress disorder is poorly documented. C_LIO_LITraumatic flashbacks can occur during esketamine administration. C_LIO_LIEsketamine-induced traumatic flashbacks does not hinder its clinical response. C_LI Clinical impact statementEsketamine nasal spray is recently validated for treatment-resistant depression (TRD). Its efficacy on comorbid post-traumatic stress disorder (PTSD) is poorly documented. In this study, we reported the data of 22 adult patients who received esketamine nasal spray for TRD with comorbid PTSD and experienced flashbacks during esketamine sessions. These flashbacks did not appear to be a contreindication to the administration of esketamine and clinical response was observed both for depression and PTSD. Our results suggest that esketamine could be safely administered to patients with comorbid PTSD and TRD and that esketamine could lead to a substantial improvement in this population.