Joelle Micallef

• MD, PhD
• Professor at Aix-Marseille University

Introduction: The use of weight loss supplements is increasing, often driven by online marketing. However, many of these supplements are adulterated with undeclared pharmaceutical substances, potentially posing significant health risks. We investigated the presence of sibutramine and sildenafil in weight loss supplements and assessed the associate...

In recent years, pregabalin has received growing attention due to its abuse liability. The aim of this study was to further characterize patterns of pregabalin users from substance abuse treatment facilities and detect changes in users profile over the study period. The data source was the Observation des Produits Psychotropes Illicites ou Détourné...

Background Several studies have focused on the use of triptan and the risk of acute vascular events but the existence of such association is still debated and has never been quantified in patients over 65 years. To assess whether triptan use among older is associated with an increased risk of hospitalization for acute vascular events. Methods A pr...

Background The combination dextropropoxyphene/paracetamol (DXP/P) was the most prescribed opioid analgesic until its withdrawal in 2011. Objectives This study investigated dispensations of analgesics in chronic users of DXP/P during the 18 months following its withdrawal. Methods A cross‐sectional study repeated yearly was conducted by using the...

Cannabis may have therapeutic benefits to relieve symptoms of amyotrophic lateral sclerosis (ALS) thanks to its pleiotropic pharmacological activity. This study is the first to present a large questionnaire-based survey about the "real-life" situation regarding cannabis use in the medical context in ALS patients in France. There were 129 respondent...

Introduction: Artificial intelligence (AI) based tools offer new opportunities for pharmacovigilance (PV) activities. Nevertheless, their contribution to PV needs to be tailored to preserve and strengthen medical and pharmacological expertise in drug safety. Areas covered: This work aims to describe PV tasks in which the contribution of AI and i...

Introduction: Due to the risk of overdoses increase especially with methadone, a reinforced monitoring has been set up by the French Addictovigilance Network following the first lockdown related to coronavirus disease 2019 (COVID-19). In this context, we managed a specific study to analyze overdoses related to methadone in 2020 compared to 2019....

Aims: To present the first nationwide, systematic, repeated assessment of doctor shopping (i.e. visiting multiple physicians to be prescribed the same drug) for more than 200 psychoactive prescription drugs, over 10 years in the 67 million inhabitants in France. Design: Nationwide, repeated cross-sectional study. Setting and Participants Data fr...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic virus was a "health crisis" and a significant burden also for the French pharmacovigilance system. It took its toll in 2 phases, the first being in early 2020 when very little was known, and during which the missions of the 31 Regional Pharmacovigilance Centers (RPVCs) from un...

Aim of the study: Post-mRNA coronavirus diseases 2019 (COVID-19) vaccines myocarditis emerged as a rare adverse effect, particularly in adolescents and young adults, and was labeled as such for both vaccines in the summer of 2021. This study aims to summarize the timeline and process of signal detection, substantiation, and quantification of myoca...

Introduction: Two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines, tozinameran/BNT162b2 (Comirnaty®, Pfizer-BioNTech) and elasomeran/mRNA-1273 (Spikevax®, Moderna), were approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) at the end of 2020, less than a year after th...

The pandemic subsequent to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus resulted, for the French institutional pharmacovigilance, in a "health crisis" in 2 phases: the coronavirus disease 2019 - "COVID-19" phase during which the missions of the Regional Pharmacovigilance Centres (RPVC) were to detect a possible impact of d...

The French health insurance data warehouse named SNDS is one of the largest medico-administrative in the world allowing for powerful pharmacoepidemiological studies, based on real-life data collected prospectively. In addition to the absolute necessity of a strong pharmacological rationale, recommendations have been thought to improve the quality o...

The French health insurance data warehouse named SNDS is one of the largest medico-administrative in the world allowing for powerful pharmacoepidemiological studies, based on real-life data collected prospectively. In addition to the absolute necessity of a strong pharmacological rationale, recommendations have been thought to improve the quality o...

In 2018, les “Ateliers de Giens” (Giens Workshops) devoted a workshop to artificial intelligence (AI) and led its experts to confirm the potential contribution and theoretical benefit of AI in clinical research, pharmacovigilance, and in improving the efficiency of care. The 2022 workshop is a continuation of this reflection on AI and intelligent a...

Résumé Les Ateliers de Giens avaient consacré en 2018 une table ronde à l’intelligence artificielle (IA) et conduit ses experts à confirmer l’apport potentiel et le bénéfice théorique que représente l’IA en recherche clinique et en matière d’amélioration de l’efficience de soins. La table ronde de 2022 s’inscrit dans la continuité de cette réflexio...

Introduction Nous avons récemment observé un nombre important de complications sanitaires associés à la consommation de clonazépam et prégabaline. L’objectif était de décrire les caractéristiques sociodémographiques, cliniques et analytiques de ces patients. Matériel et méthode Les données étaient issues des observations cliniques notifiées au CEI...

Pharmacovigilance and pharmacoepidemiology studies regarding the sex difference in adverse drug reactions are numerous, and it is now a challenge to take them into account in order to increase drug safety. Here, we present an overview of this topic through data on epidemiology, mechanisms, and methods used for assessing sex differences in drug safe...

Context: Substance use disorders during pregnancy are associated with antenatal, neonatal and long-term adverse drug reactions in children. The aim of this study was to describe, using data from OPPIDUM survey, the evolution of illicit substance use or diverted prescription drug use among pregnant women visiting French addiction care centres from...

Aims: Palbociclib has been approved in combination with endocrine therapy (ET) for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), regardless of age. Even though ABC is one of the most prevalent cancers in older patients, very few patients ≥ 65 years old were included in pivota...

[This corrects the article DOI: 10.1016/j.lanepe.2022.100393.].

The study aim was to assess the abuse/misuse potential of second‐generation antipsychotics (SGAPs) using VigiBase data. We extracted individual case safety reports of “Drug abuse, dependence and withdrawal” involving SGAPs up to June 2018. We assessed disproportionate reporting by calculating the information component, considering the lower end of...

Introduction: At the beginning of the COVID-19 epidemic, the French Addictovigilance Network alerted on the need to facilitate access to methadone, while maintaining the safety of its use, to avoid the occurrence of overdoses and deaths. The impact of the lockdown on methadone-use related hospitalizations (MUH) has not been analyzed at the national...

Introduction: Adverse drug reaction reports are usually manually assessed by pharmacovigilance experts to detect safety signals associated with drugs. With the recent extension of reporting to patients and the emergence of mass media-related sanitary crises, adverse drug reaction reports currently frequently overwhelm pharmacovigilance networks. A...

Background: Multisystem inflammatory syndrome in children (MIS-C) is the most severe clinical entity associated with pediatric SARS-CoV-2 infection with a putative role of the spike protein into the immune system activation. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. We aimed to assess the risk of hyper-infl...

Medical use of cannabis has been receiving growing attention over the last few decades in modern medicine. As we know that the endocannabinoid system is largely involved in neurological disorders, we focused on the scientific rationale of medical cannabis in three neurological disorders: amyotrophic lateral sclerosis, Parkinson’s disease, and Alzhe...

Aims The aim of this paper is to assess recent developments in non‐medical tramadol use, tramadol use disorder, illegal procurement and deaths. Methods This study used repeated cross‐sectional analysis of data collected nationwide from 2013 to 2018. Analysis was conducted through multisource monitoring of the French Addictovigilance Network of: (1...

Background.- Methylphenidate is indicated for attention deficit hyperactivity disorder (ADHD). Several studies have evaluated its abuse in specific populations (students, drug users) and few in the general population. This work describes the extent of its abuse in a region of more than 5 million inhabitants. Method.- Based on regional health insura...

Résumé Les connaissances scientifiques relatives au cannabidiol (CBD) nous apportent la preuve chaque jour que le CBD est une substance qui n’est pas inerte pharmacologiquement. S’il n’agit pas ou très peu sur les récepteurs cannabinoïdes (ceux où se fixe le tetrahydrocannabidol, THC), il agit au niveau d’autres récepteurs cérébraux, notamment à la...

Importance. Multisystem inflammatory syndrome in children (MIS-C) is the most severe life-threatening clinical entity associated with pediatric SARS-CoV-2 infection. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. Objective. To assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in child...

In the code of public health, misuse is defined as intentional and inappropriate use of a medicine or product, which is not in accordance with the terms of the marketing authorisation or the registration as well as with good practice recommendations. Very often this involves an individual or the interaction of several individuals including the pati...

The BDNF Val66Met gene polymorphism is a relevant factor explaining inter-individual differences to TMS responses in studies of the motor system. However, whether this variant also contributes to TMS-induced memory effects, as well as their underlying brain mechanisms, remains unexplored. In this investigation, we applied rTMS during encoding of a...

Résumé Le mésusage est défini dans le code de santé publique comme une utilisation intentionnelle et inappropriée d'un médicament ou d'un produit, non conforme à l'autorisation de mise sur le marché ou à l'enregistrement ainsi qu'aux recommandations de bonnes pratiques. On retrouve un acteur ou plus souvent l’interaction de plusieurs acteurs parmi...

Background During isotretinoin treatment, special attention is required to detect any symptom or change in mental health. The monitoring is complex among adolescents because of confounding factors such as mood changes associated with adolescence and puberty and a higher psycho-social impairment due to acne itself. Objectives Our goal was to determ...

Myocarditis and pericarditis may constitute adverse reactions of mRNA COVID‐19 vaccines. This study aimed to document these reactions and to assess the association with patient sex and age. This is as an observational retrospective study using a case–non‐case design (also called disproportionality study) on inflammatory heart reactions reported wit...

Le Cannabidiol (CBD) est l’un des principaux phytocannabinoïdes présent dans Cannabis sativa, avec le THC. A ce jour, un seul produit contenant uniquement du CBD (nom de ce médicament Epidyolex®) est disponible sur le marché français, son Autorisation de Mise sur le Marché (AMM) lui conférant une indication médicale en association au clobazam dans...

Background Accumulating evidence shows that some antidepressants are abused for their psychostimulant effects, but the extent of antidepressants abuse is unknown in subjects with opioid use disorders (OUD). Objectives To assess the prevalence of antidepressant abuse and its correlates in subjects with OUD. Methods Subjects ≥ 18 year-old in an opi...

IntroductionAnalgesics are among the most widely used drugs worldwide. This study describes the population treated with narcotic analgesics, their therapeutic indications and how the data have evolved over a decade.MethodsA cross-sectional, national, multicentre survey study was conducted that included surveys taken every year from 2007 to 2019 in...

INTRODUCTION: Analgesics are among the most widely used drugs worldwide. This study describes the population treated with narcotic analgesics, their therapeutic indications and how the data have evolved over a decade. METHODS: A cross-sectional, national, multicentre survey study was conducted that included surveys taken every year from 2007 to 201...

Résumé En soixante ans, les benzodiazépines ont pris le relais des barbituriques et se sont imposées dans le monde entier. La France est l’un des plus gros consommateurs au monde avec plus de 13 % de sa population exposée à cette classe pharmacologique. Dans ce contexte de surconsommation, l’objectif de cet article est de rappeler, de façon synthét...

Background To counter the COVID-19 pandemic, mRNA vaccines, namely tozinameran and elasomeran, have been authorized in several countries. These next generation vaccines have shown high efficacy against COVID-19 and demonstrated a favorable safety profile. As widespread vaccinations efforts are taking place, incidents of myocarditis and pericarditis...

Opioid analgesics and maintenance treatments, benzodiazepines and z-drugs, and other sedatives and stimulants are increasingly being abused to induce psychoactive effects or alter the effects of other drugs, eventually leading to dependence. Awareness of prescription drug abuse has been increasing in the last two decades, and organizations such as...

We described ceftriaxone-induced CNS adverse events through the largest case series of Adverse Drug Reactions (ADRs) reports, from 1995 to 2017, using the French Pharmacovigilance Database. In total, 152 cases of serious CNS ADRs were analyzed; 112 patients were hospitalized or had a prolonged hospitalization (73.7%), 12 dead (7.9%) and 16 exhibite...

In this special issue, we present the main highlights of the first weeks of pharmacovigilance monitoring of coronavirus disease 2019 (COVID-19) vaccines in this unprecedented situation in France: the deployment of a vaccination during an epidemic period with the aim of vaccinating the entire population and the intense pharmacovigilance and surveill...

Adverse drug reaction (ADR) reporting is a major component of drug safety monitoring; its input will however only be optimized if systems can manage to deal with its tremendous flow of information, based primarily on unstructured text fields. The aim of this study was to develop an automated system allowing to code ADRs from patient reports. Our sy...

Few data are available on the clinical impact of drug–drug interactions (DDIs). Most of the studies are limited to the analysis of exposure to potential DDI or the targeted impact of the combination of a few drugs or therapeutic classes. The analysis of adverse drug reaction (ADR) reports could be a mean to study generally the adverse effects ident...

Background Sickle cell disease (SCD) induces chronic haemolytic anaemia and intermittent vaso-occlusion that results in tissue ischaemia causing acute, severe pain episodes that can lead to frequent hospitalizations. These consequences can have repercussions on family, social, school and/or professional life. Here, we present some of the results of...

Introduction Le dextropropoxyphène (DXP) était l’antalgique opioïde faible le plus prescrit jusqu’à son retrait en 2011. L’objectif de cette étude est de décrire les délivrances d’antalgiques chez les utilisateurs chroniques de DXP au moment du retrait et pendant 18 mois suivant le retrait du DXP. Méthodes Ce projet est dérivé de l’étude DANTE [1]...

Introduction L’usage de produits psychoactifs illicites ou médicamenteux détournés pendant la grossesse entraîne des risques avérés de complications. Néanmoins, nous manquons de données épidémiologiques actualisées sur les tendances de consommation des femmes enceintes en France. L’objectif principal de cette étude était de décrire l’évolution des...

Introduction Le méthylphénidate, médicament psychostimulant, est indiqué dans le trouble déficitaire de l’attention avec hyperactivité chez l’enfant de 6 ans et plus. Plusieurs études ont évalué son abus dans des populations spécifiques (étudiants, usagers de drogues) et peu en population générale [1]. Ce travail décrit différents profils d’usage d...

Introduction La tendance à l’obtention illégale de médicaments se diversifie et concerne de plus en plus de molécules. L’objectif de notre étude est de déterminer quels médicaments psychoactifs sont obtenus illégalement et par quels modes d’acquisition. Méthode OPPIDUM (observation des produits psychotropes illicites ou détournés de leur utilisati...

Introduction Depuis sa commercialisation, les modalités d’accès à la méthadone sont encadrées en raison de ses propriétés pharmacologiques et du risque de surdosage. Suite au confinement, une surveillance renforcée est mise en place en raison du risque d’augmentation des surdosages : changement d’organisation des CSAPA ; mise en place de mesures dé...

Introduction La méthadone est indiquée chez les adultes et adolescents de plus de 15 ans comme traitement substitutif des pharmacodépendances majeures aux opioïdes. Suite à la présentation à l’ANSM en mars 2020 de plusieurs cas marquants d’addictovigilance en lien avec la consommation de méthadone chez des mineurs une expertise a été réalisée. Mét...

Introduction D’après les rapports périodiques d’addictovigilance de la prégabaline, son usage problématique s’intensifie en France depuis 2018. Ce travail décrit l’évolution de différents indicateurs d’abus et les complications cliniques liées à l’abus de prégabaline, d’après les données recueillies par le réseau français d’addictovigilance. Métho...

Introduction: Gabapentinoid drugs (gabapentin and pregabalin) are widely used worldwide for epileptic and pain disorders. First signals of gabapentinoid abuse occurred in the last decade. This study aims to describe clinical characteristics of gabapentinoid use related disorders and health consequences in France. Materials and Methods: We designed...

The current COVID-19 pandemic is an exceptional health situation including for drug use. As there was no known effective drug for COVID-19 at the beginning of the pandemic, different candidates were proposed. In this short article, we present the French public pharmacovigilance activities during this health crisis. Although COVID-19 is a confoundin...

Objectif La méthamphétamine est un psychostimulant puissant, dont la longue durée d’action en fait une substance attractive. Utilisée sous différentes voies (intraveineuse, fumée ou inhalée), elle est responsable d’effets toxiques cardiovasculaires et neuropsychiatriques fréquents pouvant aller jusqu’au décès. Le trouble de l’usage (TU) de méthamph...

Objectifs L’addiction étant caractérisée par un comportement de recherche de substances, l’analyse des modes d’obtention des médicaments est un proxy pour évaluer leur usage non médical. Dans le contexte du doublement des ventes de prégabaline au cours de la dernière décennie, [1], [2] l’objectif de cette étude est d’évaluer la tendance de l’obtent...

Parmi les opioïdes, l’utilisation de l’oxycodone a significativement augmenté en France au cours de la dernière décennie [1]. Un comportement de doctor shopping (c’est-à-dire un chevauchement de prescriptions de plusieurs prescripteurs pour un même médicament) a été identifié dans plusieurs régions, ce qui suggère notamment une recherche de doses é...

Objectifs En raison de ses spécificités pharmacologiques, le maniement de la méthadone est complexe et les sujets sont plus exposés à un risque de surdosage. Dans ce contexte, les modalités d’accès de la méthadone été encadrées dès sa commercialisation et un suivi national d’addictovigilance été mis en place afin d’évaluer les risques liés à cette...

Objectifs De nos jours, de plus en plus de médicaments sont obtenus illégalement. L’objectif de notre étude est de déterminer quels sont les médicaments psychoactifs obtenus illégalement et quels sont les modes d’acquisition. Méthode OPPIDUM (Observation des Produits Psychotropes Illicites ou Détournés de leur Utilisation Médicamenteuse) est un di...

Clinical trials involving brain disorders are notoriously difficult to set up and run. Innovative ways to develop effective prevention and treatment strategies for central nervous system (CNS) diseases are urgently needed. New approaches that are likely to renew or at least modify the paradigms used so far have been recently proposed. Quantitative...

Doctor shopping enables subjects to receive more than the prescribed dose out of any medical management, which suggests a search for high doses, and makes doctor shopping a relevant proxy for misuse and potential abuse. Therefore, this study aimed to identify and characterize profiles of subjects with doctor-shopping behavior for methylphenidate in...

This nationwide study aimed to compare use of oxycodone and doctor shopping for oxycodone in 2010 and 2016, and to quantify doctor shopping for oxycodone by sex, age, formulation, and dosage in 2010 and 2016. This study is a cross-sectional comparative analysis of doctor shopping based on all dispensings of oxycodone in France, in 2010 and 2016. Di...

Aims Analgesics are the most widely used medicines worldwide. In parallel, opioid abuse has increased and is of major concern. The accessibility of pharmacologically powerful medicines and the addictovigilance signals in France about the risk of opiates addiction call for an overview of analgesic use. The objective of this study was to investigate...