François Montastruc

Purpose Pharmacovigilance Centres (PVCs) provide independent drug information to healthcare professionals in addition to their pharmacovigilance activities. However, their impact on clinical decision-making has been poorly studied. This study assessed the impact of a French PVC on clinical management in a tertiary university hospital (Toulouse University Hospital). Methods We conducted a retrospective observational study including all drug-related enquiries submitted to the Toulouse PVC during 2024. Impact was evaluated according to three predefined criteria: whether the enquiry was submitted before or after a clinical management decision had been made, concordance between PVC recommendations and subsequent clinical management, and documentation of the advice in the electronic patient record. Based on these criteria, impact was classified as certain, probable, or uncertain for enquiries submitted before clinical management, and as confirmatory (validating an already implemented decision) or uncertain for enquiries submitted after clinical management had already been initiated. Results A total of 128 enquiries were analysed. Most concerned adverse drug reactions (111/128), involved hospitalised patients (100/128), and originated from a broad range of clinical departments, mainly geriatrics (14/128), gastroenterology (11/128), neurology (11/128), infectious diseases (10/128) and internal medicine (10/128). Overall, clinical management was concordant with PVC recommendations in 87% of cases. Among the 92 pre-decision enquiries, PVC impact was classified as certain in 62% and probable in 24% of cases. Among the 36 post-decision enquiries, PVC advice was confirmatory in 44% of cases. The enquiries also generated 50 pharmacovigilance reports, including one potential safety signal. Conclusion PVCs support both clinical decision-making and drug safety surveillance.

Aim: This study aimed to compare how Norwegian healthcare professionals (HCPs) and consumers reported the same adverse event (AE) following immunization with vaccines against COVID‐19 during the COVID‐19 pandemic. Specifically, we aimed to compare the extent to which HCPs and consumers reported information relevant for assessing the causal relationship between the AE and the suspected COVID‐19 vaccine, with a particular focus on the type of unstructured information provided by each group. Methods: Verified duplicate pairs of AE reports following COVID‐19 vaccination were extracted from the Norwegian Adverse Drug Reaction Registry. Free‐text case narratives were analysed using thematic analysis to categorize types of unstructured information. A scoring system quantified completeness of causality‐relevant information, with final scores categorized into levels of completeness. Time intervals from AE onset to reporting were also calculated. Results: Nineteen categories of unstructured information were identified. HCPs more often provided vaccine dose details, clinical observations, test results and causality reflections, while consumers more often described dietary supplements, life consequences and subjective AE explanations ( p < .05). In 85% of 127 duplicate pairs, HCPs and consumers provided at least 50% complementary information in free‐text narratives. Both groups provided similar levels of causality‐relevant information ( p = .774). HCPs reported earlier than consumers ( p < .05). Conclusion: HCPs and consumers provided highly complementary unstructured information and comparable completeness for causality assessment. Collaboration between these groups should be encouraged, particularly in public health and clinical emergencies like epidemics and in situations of high uncertainty.

Notre travail porte sur l’évaluation de l’utilisation et des risques associés aux neuroleptiques en population générale. Nous avons organisé notre travail selon deux approches. D’abord, de façon classique en pharmaco-épidémiologie, une « approche « pragmatique » a permis d’étudier en « vie réelle », (i) l’utilisation des neuroleptiques dans la population générale en France à partir des données de l’Echantillon Généraliste des Bénéficiaires (EGB) et de la base Midi-Pyrénées de Pharmacovigilance (BMPPV), ainsi que dans une population de femmes enceintes à partir de la base de données EFEMERIS (Evaluation chez la Femme Enceinte des MEdicaments et de leurs RISques); (ii) les risques associés à cette utilisation à partir de la BMPPV, de la base mondiale de pharmacovigilance, VigiBase® et de la base de données EFEMERIS. Deuxièmement, nous avons testé une approche originale « explicative » à partir de VigiBase®, la méthode PE-PD (PharmacoEpidémiologie-PharmacoDynamie) pouvant potentiellement mettre en évidence le mécanisme d’action de certains effets indésirables. Nous avons étudié pour cela l’exemple largement connu des mouvements anormaux induits par les neuroleptiques. Pour l’approche « pragmatique », l’analyse montre une modification de l’utilisation des neuroleptiques en population générale et chez la femme enceinte, avec un report des prescriptions des neuroleptiques de première génération (NL1G) vers ceux de deuxième génération (NL2G). Si l’utilisation reste globalement stable, on note un accroissement de l’utilisation des NL2G dans deux populations vulnérables vis-à-vis des effets indésirables : les enfants/adolescents et les femmes enceintes. Malgré le report NL1G vers les NL2G, la prescription des médicaments à fort poids atropinique est élevée et stable au cours des dernières années. Concernant les risques associés, nous n’avons pas pu confirmer dans la base EFEMERIS, le signal retrouvé dans VigiBase de malformations congénitales gastro-intestinales avec les neuroleptiques. Pour les mouvements anormaux, le risque apparait moins important avec la clozapine qu’avec les autres neuroleptiques. Des différences existent entre les classes d’âge, avec, par exemple, moins d’akathisie, mais plus de dystonie aiguë chez les moins de 18 ans. Pour l’approche « explicative », la méthode PE-PD a permis de mettre en évidence l’un des mécanismes potentiels responsables de la réduction des mouvements anormaux sous neuroleptique, à savoir l’action antagoniste sur les récepteurs sérotoninergique 5-HT2A et muscariniques M1. Notre travail de thèse nous a permis à travers l’étude des neuroleptiques de discuter, (1) d’abord au niveau méthodologique, de la complémentarité entre les bases médicamenteuses (type EGB et EFEMERIS) et les bases de pharmacovigilance pour les études d’utilisation des médicaments et des risques associés, avec, en particulier, l’opportunité d’étudier le risque malformatif des médicaments avec les bases de pharmacovigilance. Ensuite, (2), au niveau pharmacologique, de mettre en évidence la problématique du poids atropinique des prescriptions associées aux neuroleptiques sur les bénéfices et/ou les dommages. Enfin, (3), dans une approche de pharmacologie sociale, en partant des résultats de la méthode PE-PD, de discuter de la place du mécanisme d’action des médicaments dans leur évaluation, de la pharmacologie fondamentale, en passant par la pharmacologie clinique, et de son éventuelle intégration en pharmaco-épidémiologie.

Introduction Use of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) has significantly increased due to their cardiovascular benefits. Whether SGLT-2is increase risk of cancer has been of concern since first clinical trials, but this question remains unclear because of methodological limitations in previous studies. Methods We conducted a disproportionality analysis using Vigibase^® between 2014 and 2023 to estimate the association between SGLT-2i use and the risk of reporting of different subtypes of cancers, compared with glucagon like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors. Results Among 644 reported cases of cancer associated with SGLT-2i use, 427 (66.3%) were male, with a mean age of 66.5 ± 9.7 years. Sodium-glucose cotransporter 2 inhibitors showed increased reporting odds ratio for bladder cancer (ROR 4.46, 95% CI 3.23–6.17) and kidney cancer (ROR 1.84, 95% CI 1.25–2.69), but not for all other cancer subtypes. Conclusion In this disproportionality analysis with a hypothesis-generating approach, SGLT-2is are associated with an increased risk of reporting bladder and kidney cancer. There is a need of an urgent clarification of this signal with further long-term observational studies. Graphical Abstract Graphical abstract of the study design and results. CI confidence interval, DPP-4i dipeptidyl peptidase 4 inhibitors, GLP-1a glucagon-like peptide 1 agonists, ROR reporting odds ratio, SGLT-2is sodium-glucose cotransporter 2 inhibitors

Background: Catatonia in psychotic patients presents unique challenges. While antipsychotics are the cornerstone of schizophrenia treatment, their use in catatonic patients is sometimes discouraged for fear of worsening the signs. Reports on the successful use of second-generation antipsychotics have been published. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to describe the outcomes of antipsychotic-treated catatonic events. Methods: We searched Medline and Web of Science databases from 2000 to 2023 using search terms including “catatonia” and “antipsychotic agents” for all original peer-reviewed articles, including clinical trials, observational studies, and case-reports. We included antipsychotic-treated catatonic events and extracted data on patient characteristics, pharmacological context, agent involved, and treatment outcomes for each antipsychotic trial. Results: After screening 6,219 records, 79 full-text articles were included. Among them, we identified 175 antipsychotic trials (in 110 patients). Only 41.1% of the patients benefited from a previous benzodiazepine trial. Antipsychotic use was considered beneficial in 60.0% of the trials, neutral in 29.1%, and harmful in 10.9%. Trials tended to be reported as beneficial for amisulpride, clozapine, and risperidone, equivocal for aripiprazole and olanzapine, and mostly detrimental for haloperidol and quetiapine. Psychotic disorders were the most common underlying etiology (65.8%). Conclusions: Antipsychotics could be an option in the treatment of catatonia in psychotic patients. However, with few exceptions, we found non-beneficial outcomes with all second-generation antipsychotics in varying proportions in this largest review to date. Although olanzapine is widely used, it is associated with mitigated reported outcomes.