[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.

Towards personalized pharmacology: Antipsychotics and schizophrenia.

Since the discovery of the first antipsychotic in 1952, many antipsychotic drugs have been developed, each with different pharmacokinetic and pharmacodynamic properties. The pharmacological heterogeneity of antipsychotic drugs should allow a personalized drug prescription adapted to the different clinical picture of schizophrenia. Schizophrenia is a chronic disease, during which 3 stages of pharmacological intervention can be identified: the first episode psychotic (FEP), the phase of therapeutic stabilization that can progress to situations of resistance, and the question of long-term prescription. During FEP, the choice of the first antipsychotic treatment seems to be underpinned by its safety profile in relation to the patient for whom it is prescribed, according to the adage start low and go-slow. The therapeutic stabilization phase is based on treatment optimization through a rigorous evaluation of the benefits-harm balance, with the use of tools such as personalized therapeutic drug monitoring and pharmacogenetics. Generally speaking, while some antipsychotic drugs seem to present a more favorable efficacy profile in certain situations, the differences are small, whereas the differences in safety are more important and should be considered in the first line. Individual factors such as the presence of co-morbidities, as well as previously experienced treatments must also be taken into account. Finally, the question of maintaining the prescription of antipsychotic drugs over the long term arises in view of the iatrogenic risk with controversial current data. Overall, the personalized prescription of antipsychotic drugs in schizophrenia remains limited by a lack of data in the literature, justifying the development of clinical studies in this field. But at present, the dogma remains that of primum non nocere.

Interest of pharmacoepidemiology for pharmacodynamics and analysis of the mechanism of action of drugs.

Pharmacology is often divided in separate branches, such as molecular and cellular pharmacology, pharmacokinetics, pharmacodynamics, experimental and/or preclinical pharmacology, clinical pharmacology (and therapeutics), pharmacogenetics, pharmacogenomics, pharmacovigilance, pharmacoepidemiology, pharmacoeconomics… This enumeration gives a global picture of different scientific areas, which are however dealing with the same question. Another mindset should be a global interactive and continuous approach, which could be designed as "human pharmacology". An original and attractive way to illustrate this continuous approach is to combine pharmacodynamics and pharmacovigilance and/or pharmacoepidemiologic data. Coupling disproportionality analyses in pharmacovigilance databases or computerized health databases, with pharmacological characteristics of drugs (receptor affinity, for example) allows investigating in humans, the mechanism of adverse drug reactions. Examples of such analyses investigating the risk of movement disorders, diabetes related to psychoactive drugs, or the risk of adverse cardiac outcomes with different drugs (classical drugs or protein kinase inhibitors) are given. The increasing number of research works investigating this topic underlines the importance of this relatively new approach, which gives significant inputs for the better knowledge of drug safety.

Abatacept initiation in rheumatoid arthritis and the risk of cancer: a population-based comparative cohort study.

OBJECTIVE: To assess whether abatacept as initial biological DMARD (bDMARD) in the treatment of RA, when compared with other bDMARDs, is associated with an increased risk of cancer overall and by specific cancer sites (breast, lung, lymphoma, melanoma and non-melanoma skin cancer). METHODS: We performed a population-based cohort study among patients newly treated with bDMARDs within the US-based Truven MarketScan population and Supplemental US Medicare from 2007 to 2014. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs of any cancer (and specific cancers) associated with initiation of abatacept, compared with initiation of other bDMARDs, adjusted for age and deciles of the propensity score. RESULTS: The cohort included 4328 patients on abatacept and 59 860 on other bDMARDs, of whom 409 and 4197 were diagnosed with any cancer during follow-up (incidence rates 4.76 per 100 per year and 3.41 per 100 per year, respectively). Compared with other bDMARDs, the use of abatacept was associated with an increased incidence of cancer overall (hazard ratioadjusted 1.17; 95% CI 1.06, 1.30). Analyses by specific cancer sites showed a significantly increased incidence of non-melanoma skin cancer (hazard ratioadjusted 1.20; 95% CI 1.03, 1.39), but no significant difference for other specific cancer sites. CONCLUSION: The use of abatacept as first bDMARD in the treatment of RA was associated with a slight increased risk of cancer overall and particularly non-melanoma skin cancer, compared with other bDMARDs. This potential signal needs to be replicated in other settings.

Trends and Patterns of Antidepressant Use in French Children and Adolescents From 2009 to 2016: A Population-Based Study in the French Health Insurance Database.

PURPOSE/BACKGROUND: Over the last decade, the use of antidepressants (ATDs) in children and adolescents has markedly increased in several occidental countries, but recent data in French children are missing. This study aimed to assess trends of ATD use in French children (6-11 years) and adolescents (12-17 years) and to characterize changes in ATD prescribing patterns from 2009 to 2016. METHODS: Using data from the French Health Insurance Database, annual prevalence and incidence of ATD use and changes in ATD prescribing patterns were analyzed. RESULTS: Overall ATD prevalence of use rose slightly from 0.51% in 2009 to 0.53% in 2016 (+3.9%), with a decrease in children (0.18%-0.11%; -38.9%) and an increase in adolescents (0.86%-0.98%; +14.0%) and an overall female preponderance (56.7% in 2009; 58.7% in 2016). Serotonin reuptake inhibitor prevalence of use increased from 0.24% to 0.34%, whereas tricyclic ATD use decreased (from 0.20% to 0.16%). Similar trends were obtained with overall incidence of use, from 0.39% in 2009 to 0.36% in 2016 (-7.7%). Sertraline was the most frequently prescribed in adolescents (2009: 22.2% of all ATD prescriptions; 2016: 32.9%), whereas amitriptyline was the most prescribed in children (2009: 42.7% and 2016: 41.2%). Off-label use decreased in adolescents (from 48.4% to 34.8%) but increased in children (from 10.0% to 26.5%). IMPLICATIONS/CONCLUSIONS: Antidepressant level of use in French children and adolescents was stable in recent years and lower than that observed in other European countries and the United States.

Interactions between medical residents and drug companies: a national survey after the Mediator® affair.

BACKGROUND: The present study aimed to describe exposure and attitudes of French medical residents towards pharmaceutical industry. The study was performed shortly after the Mediator affair which revealed several serious conflicts of interest inside the French health system. METHODS AND FINDINGS: A cross-sectional study was implemented among residents from 6 French medical faculties. Independent education in pharmacology, attitudes towards the practices of pharmaceutical sales representatives, opinions concerning the pharmaceutical industry, quality of information provided by the pharmaceutical industry, and opinions about pharmaceutical company sponsorship were investigated through a web-based questionnaire. We also assessed potential changes in resident attitudes following the Mediator affair. The mean value of exposure to drug companies was 1.9 times per month. Global opinions towards drug company information were negative for 42.7% of the residents and positive for only 8.2%. Surprisingly, 81.6% of residents claimed that they had not changed their practices regarding drug information since the Mediator affair. Multivariate analyses found that residents in anesthesiology were less likely to be exposed than others (OR = 0.17 CI95% [0.05-0.61]), exposure was significantly higher at the beginning of residence (p<0.001) and residents who had a more positive opinion were more frequently exposed to drug companies (OR = 2.12 CI95% [1.07-4.22]). CONCLUSIONS: Resident exposure to drug companies is around 1 contact every 2 weeks. Global opinion towards drug information provided by pharmaceutical companies was negative for around 1 out of 2 residents. In contrast, residents tend to consider the influences of the Mediator affair on their practice as relatively low. This survey enabled us to identify profiles of residents who are obviously less exposed to pharmaceutical industry. Current regulatory provisions are not sufficient, indicating that further efforts are necessary to develop a culture of disclosure of conflict of interest and of transparency in residents.