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Objective: ESKALE is a French, multicentre, observational study of adults with treatment-resistant depression (TRD) treated with esketamine. This interim analysis describes baseline demographic and clinical characteristic evolution in patients included and treated from early access program to post-marketing launch., Methods: Data were collected from medical records and included patient characteristics, disease history at esketamine initiation, use of neurostimulation, the patient's care pathway, and the number of antidepressant treatment lines prescribed prior to esketamine initiation. Descriptive statistics were used for each cohort: the early access program 'Temporary Authorisation for Use' (ATU), post-ATU, and post-launch cohorts., Results: The overall ESKALE cohort ( N  = 160 included; n  = 157 treated with esketamine; average age 49.0 years; 66.2% female) demonstrated moderate-to-severe depression according to clinical assessment and a mean Montgomery-Åsberg Depression Rating Scale score of 32.6 (8.0); however, severity, subtype, and comorbidities were heterogeneous across the cohorts. Earlier use of esketamine and prior to alternative treatments occurred during the later cohorts., Conclusion: These findings demonstrated a high burden of TRD in these patients and that esketamine is used in TRD treatment regardless of their disease severity, subtype, or existing comorbidities. These results also suggest that esketamine is potentially a clinically useful alternative treatment, particularly with healthcare professionals gaining greater familiarity with and easier access to esketamine.

Background: Posttraumatic 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., Objectives: Our main objective was to describe esketamine-induced traumatic flashbacks and their impact on clinical trajectories within a sample of patients with comorbid TRD-PTSD., Methods: We 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., Results: Between 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%)., 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 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., Competing Interests: Conflict of interest Most of the authors of this article received honoraria or consulting fees from Janssen-Cilag (MR, LM, MH, JH, SB, MD, EO, BG, AS, RG, RR, DZ, LS, OG, AL, LB) with no financial or other relationship relevant to the subject of this article.

Background: The efficacy of esketamine in treatment-resistant depression (TRD) has been confirmed. However, its administration is expensive and restrictive, with limited knowledge on how long the treatment should be continued. Predicting the treatment outcome would benefit patients and alleviate the global treatment cost. We aimed to define distinct trajectories of treatment response and assess their predictability., Methods: In this longitudinal study, two independent samples of patients with unipolar or bipolar TRD were treated with esketamine in real-world settings. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) before each esketamine administration. Latent class analyses were used to define trajectories of response., Results: In the original sample (N = 50), we identified two classes whose trajectories depicted response and non-response, respectively. The model was validated in the confirmatory sample (N = 55). Class membership was influenced by a few baseline characteristics such as concomitant benzodiazepine medication, number of depressive episodes or polarity. On the other hand, after only two esketamine administrations, the MADRS score predicted the 90-day trajectory of response with an accuracy of 80 %., Limitations: This observational study is not placebo-controlled. Therefore, its results and their generalizability need to be confirmed in experimental settings., Conclusions: After the first administrations of esketamine, the MADRS score has a good capacity to predict the most plausible trajectory of response. While thresholds and their predictive values need to be confirmed, this finding suggests that clinicians could base on MADRS scores their decision to discontinue treatment because of poor remaining chances of treatment response., Competing Interests: Declaration of competing interest PG received during the last 5 years fees for presentations at congresses or participation in scientific boards from Angelini, Janssen, Lundbeck, Otsuka and Viatris. ACP and PM received fees for presentations and congress participation from Janssen. RP has been invited by Janssen to a congress. LM has received honoraria or consulting fees from Bristol-Meyers-Squibb, Janssen, Servier, Lilly and Otsuka. RG has received compensation as a member of the scientific advisory board of Janssen, Lundbeck, Roche, SOBI, and Takeda, has served as a consultant and/or speaker for AstraZeneca, Boehringer Ingelheim, Pierre Fabre, Lilly, Lundbeck, LVMH, MAPREG, Novartis, Otsuka, Pileje, SANOFI, and Servier and received compensation. He has also received research support from Servier. FV has been invited to scientific meetings, consulted and/or served as a speaker, and received compensation from Lundbeck, Servier, Recordati, Janssen, Otsuka, LivaNova, Chiesi, and Rovi. He has received research support from LivaNova and Lundbeck. Other authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The phenomenon of malaise is on the rise at universities, reflecting a deteriorating psychological state that is a combination of anxiety and stress factors. This psychological and emotional upheaval within students is indicative of a fundamental existential issue. In fact, hidden behind the choice of an educational program is the significance given by the student to their life goals. It is this dimension of attributing meaning to one's education and, more broadly, to one's life (the existential dimension) that we have sought to explore. We hypothesized that a stable investment in one's life goals and a sense of psychological wellbeing during one's studies could be fostered by reflective work done alongside the educational process. Our research took the form of a mixed methodological approach to the attribution of meaning to education, including an interpretive phenomenological analysis (IPA), and the experimentation of support for the meaning of education. Four dimensions of meaning were found to be observable in varying degrees in all students, each playing a specific role. Moreover, this research has confirmed that the meaning of studies is not to be understood solely in terms of education, but is part of a singular life story. Reflective work, developing meaning, facilitated by others (advisor, teacher, etc.) can help preserve/restore the feeling of wellbeing. It should be noted that, as the work presented in this article predates the pandemic, we will not address the amplifying effects of this health crisis on existential issues, which some recent studies are beginning to highlight., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Baatouche, de Maricourt and Bernaud.)

Major depressive disorder is a complex multifactorial condition with a so far poorly characterized underlying pathophysiology. Consequently, the available treatments are far from satisfactory as it is estimated that up to 30% of patients are resistant to conventional treatment. Recent comprehensive evidence has been accumulated which suggests that inflammation may be implied in the etiology of this disease. Here we investigated ketamine as an innovative treatment strategy due to its immune-modulating capacities. In a murine model of LPS-induced depressive-like behavior we demonstrated that a single dose of ketamine restores the LPS-induced depressive-like alterations. These behavioral effects are associated with i/ a reversal of anxiety and reduced self-care, ii/ a decrease in parenchymal cytokine production, iii/ a modulation of the microglial reactivity and iv/ a decrease in microglial quinolinic acid production that is correlated with plasmatic peripheral production. In a translational approach, we show that kynurenic acid to quinolinic acid ratio is a predictor of ketamine response in treatment-resistant depressed patients and that the reduction in quinolinic acid after a ketamine infusion is a predictor of the reduction in MADRS score. Our results suggest that microglia is a key therapeutic target and that quinolinic acid is a biomarker of ketamine response in major depressive disorder., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Olanzapine long-acting injections (OLAIs) are often prescribed to patients with severe schizophrenia who are typically excluded from randomized clinical trials. To date, no mirror-image study has examined the impact of OLAIs on healthcare resource utilizations in these patients. We conducted a retrospective, one-year mirror-image study of OLAIs on 40 patients with severe schizophrenic disorder. Illness severity was defined by failure to respond to two sequential antipsychotics. Outcomes included: (i) healthcare resource utilizations via hospitalization admissions, bed days, outpatient visits, and inpatient service costs computations (ii) clinical efficacy through changes in the Brief Psychiatric Rating Scale (BPRS) and in the Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and (iii) adverse effects. After one year, OLAIs were associated with significant decreases of 65.7%, 86.2% and 86.2% in hospitalization admissions, bed days, and inpatient service costs respectively. A significant mean change of -0.47 and -0.63 was determined the BPRS and the CGI-SCH scores, respectively. There were no significant differences in the number of outpatient visits and adverse effects, except for post-injection sedation/delirium syndrome whose incidence was 0.30% per injection. This mirror-image study provides the first evidence that prescribing OLAIs reduces in a cost-effective manner average bed days and hospital admissions in patients with severe schizophrenia., (Copyright © 2018. Published by Elsevier B.V.)

Background: Research on the generalizability of clinical trials in panic disorder is limited. The present study sought to quantify the generalizability of clinical trials' results of individuals with DSM-IV panic disorder (PD) to a large community sample., Methods: Data were derived from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a large national representative sample of 43,093 adults of the United States population. We applied a standard set of eligibility criteria representative of PD clinical trials to all adults with past 12 months PD (n=907), and then to a subgroup of participants seeking treatment (n=105). Our aim was to determine the proportion of participants with PD who would have been excluded by typical eligibility criteria., Results: We found that more than 8 out of ten participants (80.52%; 95% CI=77.13-83.52%) with PD were excluded by at least one criterion. In the subgroup of participants who sought treatment, the exclusion rate by at least one criterion was higher (92.40%; 95% CI=84.60-96.42%). For the full sample and the treatment-seeking subsample, having currently a depression and a diagnosis of alcohol or drug abuse/dependence were the criteria excluding the highest percentage of participants. Having a lifetime history of bipolar disorder and a current significant medical condition also excluded a substantial proportion of individuals in both samples. Exclusion rates were similar when considering panic disorder with and without agoraphobia., Conclusions: Clinical trials, that exclude a majority of adults with panic disorder, should carefully consider the impact of eligibility criteria on the generalizability of their results. As required by CONSORT guidelines, reporting exclusion rate estimate and reasons of eligibility should be mandatory in both clinical trials and meta-analyses., (Copyright © 2012 Elsevier B.V. All rights reserved.)