Reporting of harms in clinical trials of esketamine in depression: a systematic review.

While previous systematic reviews of trials evaluating conventional antidepressants highlighted inadequacies and inconsistencies in adverse event (AE) reporting, no evaluation is available on esketamine in resistant depression. The objective of this review was to assess quality of reporting AEs in all published clinical trials studying esketamine. It also aimed to compare the proportions of AEs reported in journal articles to those recorded in the ClinicalTrial.gov Registers. Clinical trials evaluating the efficacy and safety of esketamine in depression were searched using Medline and ClinicalTrials.gov. The quality of reporting harms was assessed using a 21-item checklist from the CONSORT Extension of Harms (1 point by item). The total quality score was graded into four categories: high (17-21), moderate (12-16), low (7-11) and very low (0-6). Ten clinical trials were included in the analysis. Nine trials were classified as 'low quality' with regard to safety, one trial was classified as 'moderate quality'. Compared to AEs recorded in ClinicalTrials.gov, we found that 41.5% of serious AEs and 39% of non-serious AEs were not reported in the published articles. Among them, the majority were psychiatric events but also cardiovascular events and 94% concerned patients from esketamine groups. Quality of AEs reporting in published clinical trials of esketamine was poor and harms were reported less frequently in journal publications than in ClinicalTrial.gov Registers. The study suggests that an assessment of the benefits/risks balance of esketamine based on the results reported in trial publications is flawed due to the poor accuracy and completeness of harm data.

[Funding of psychiatry in France, the problem of expensive drugs. Example of Esketamine in the case of resistant depressive episodes]. / Financement de la psychiatrie en France, la question des médicaments onéreux : exemple de l'Esketamine dans l'épisode dépressif caractérisé résistant.

In France, the funding of mental health institutions relies on an annual budget allocation. Esketamine, a non-competitive NMDA glutamate receptor antagonist, has been approved for adults with treatment-resistant major depressive disorder since 2019. However, due to its high cost (€200 per 28 mg device, excluding tax), the aim of this work was to evaluate whether the income received by an institution for the management of a patient treated with Esketamine could cover the purchase of devices, based on real clinical data. Within our institution, seven patients underwent treatment with Esketamine during the study period resulting in a total usage of 714 devices, amounting to a purchase cost of €142,800. Over the course of the follow-up period, the institution received €149,054 in revenue for the treatment of these patients. Our analysis reveals that the expense associated with Esketamine constitutes 95.8 % of the income generated from caring for these patients. This not only raises questions about the pricing of this drug but also highlights the lack of a funding system for costly psychiatric drugs. This concern extends to somatic treatments associated with psychiatric care.

Drug-induced psychiatric disorders: A pharmacovigilance update.

The psychiatric risks associated with drugs are sometimes one of the few restrictions on the use of certain drug classes, such as corticosteroids in patients with a history of severe psychotic episodes associated with this drug class. In this non-exhaustive review, we propose to deal with the most recent issues concerning psychiatric disorders induced by drugs and encountered in doctors' clinical practice. Firstly, we look at depressive disorders and suicide risks, secondly at psychotic and manic disorders and thirdly at anxiety and sleep disorders. While lot of drugs are associated with psychiatric disorders, the confounding by indication represents an important methodological gap since information on the psychiatric profile of patients is not always available. This is particularly the case for serotonin reuptake inhibitors and esketamine used as antidepressants. Recent pharmacovigilance concerns of psychiatric disorders emerged with montelukast, orexin receptor antagonists or cystic fibrosis transmembrane regulator (CFTR) modulators.