[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.

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.

Case Report: A Case of Valproic Acid-Induced Hyperammonemic Encephalopathy Associated With the Initiation of Lithium: A Re-duplicable Finding.

Introduction: Hyperammonemic encephalopathy (HAE) is a serious adverse effect of valproate semisodium, which is facilitated by the potential for drug interaction. However, despite frequent co-prescription of valproate semisodium and lithium, the role of this combination in the occurrence of HAE has not been defined in the literature. This case report concerns the occurrence of HAE concomitant with the initiation of lithium in a 29-year-old patient who had been placed on valproate semisodium for a schizoaffective disorder. Case Report: Due to a relapse while on a combined antipsychotic and mood-stabilizing therapy (paliperidone palmitate and valproate semisodium), a cross-taper from valproate semisodium to lithium was proposed. The initiation of lithium was accompanied by an acute confusional syndrome, an elevated serum valproate level and hyperammonemia suggestive of drug-induced HAE. The discontinuation of lithium and reduction of valproate semisodium led to neurological improvement, until a recrudescence of psychiatric symptoms justified a rechallenge of the combination within the framework of a new cross-taper. As soon as Lithium was re-initiated, an increase in the serum valproate level and hyperammonemia were again noted. Discussion: The mechanisms of valproate-related HAE involve various metabolic pathways. In this case, exploration of the iatrogenic hypothesis focused on the imputability of concomitant cannabis use and co-prescriptions of benzodiazepines, antipsychotics, and in all likelihood, mood stabilizers. Conclusion: Therefore, this case study suggests that Lithium plays a role in serum valproate level elevation, and supports the hypothesis of an association between an elevated serum valproate level, hyperammonemia and reversible encephalopathy. A more in-depth pharmacokinetic exploration would provide a better understanding of the mechanisms of these interactions and support for the benefit-risk balance associated with this frequent co-prescription.

Case Report: Use of Subcutaneous Midazolam During an Episode of Catatonia.

Midazolam is a benzodiazepine (BZD) mainly used in anesthetic induction due to its pharmacokinetic features. Its place in the therapeutic management of catatonia remains to be determined. Here we present the case of a 65-year-old man who presented with a first episode of catatonia with opposition to any form of oral treatment, where a single dose of 1 mg of subcutaneous (SC) Midazolam permitted clinical improvement allowing oral treatment to be given. The patient's history notably included a renal transplant linked to Polycystic Kidney Disease (PKD) and no history of psychiatric illness nor of any use of psychotropic drugs. As the patient refused to drink or eat and ceased answering basic questions, a psychiatric assessment was required. A diagnosis of Catatonic disorder due to a general medical condition [DSM 5-293.89/ ICD10 [F06.1]] was made. A Bush-Francis Catatonia Rating Scale (BFCRS) analysis returned a score of 15 out of 62, with stupor, mutism, negativism, staring, withdrawal, rigidity, and stereotypy. As the negativism prevented the patient from taking any form of oral treatment, after a brief discussion with the unit's physician, it was decided to administer 1 mg of SC Midazolam. One hour later, the patient was more responsive and compliant, and agreed to drink, eat, and take medication. Thus, the catatonic signs of mutism, negativism, staring, and withdrawal were resolved, but waxy flexibility and catalepsy appeared, leading to a new BFCRS score of 10 out of 62. Oral treatment with 2.5 mg Lorazepam, 4 times a day, was then initiated. Midazolam could be a safer choice compared with the other options available, such as other SC BZD, considering the complex safety profile of this patient with renal insufficiency. This situation represents the first report of using SC Midazolam as an injectable treatment for catatonia. More studies are needed to assess the clinical pertinence of SC Midazolam in the treatment of catatonia.