Increase of high-risk tramadol use and harmful consequences in France from 2013 to 2018: Evidence from the triangulation of addictovigilance data.

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) validated reports of high-risk tramadol use, (2) record systems collecting information from toxicology experts investigating analgesic-related deaths (DTA) and deaths related to substance abuse (DRAMES), and pharmacists for forged prescriptions (OSIAP), and (3) survey of drug users, with investigation of patterns of use while visiting addiction-specialised institutions (OPPIDUM). RESULTS: Despite a plateauing level of tramadol exposure in the French population, the proportion of tramadol reports increased 1.7-fold (187 cases in 2018, 3.2% (95% confidence interval [CI]: 2.74-3.63%), versus 1.9% (95% CI: 1.49-2.42% in 2013). Trends were similar in OSIAP: 11.9% of forged prescriptions in 2018 (95% CI: 10.56-13.45%); 1.7-fold increase; in OPPIDUM: 0.76% (95% CI: 0.55-1.02); 2.2-fold increase; and DRAMES: 3.2% of drug abuse-related deaths in 2018 (95% CI: 1.89-5.16) versus 1.7% in 2013 (95% CI: 0.65-3.84). Tramadol was the primary opioid in analgesic-related deaths in DTA (45% in 2018). Two profiles of high-risk tramadol users were identified: (1) patients treated for pain or with tramadol persistence when pain disappeared (mainly women; mean age 44 years), and (2) individuals with non-medical use for psychoactive effects (mainly men; mean age 36 years). CONCLUSION: The triangulation of the data obtained through addictovigilance monitoring evidenced a recent increase in high-risk tramadol use. These findings have a practical impact on the limitation of the maximal duration of tramadol prescriptions.

Ten-year trend of opioid and nonopioid analgesic use in the French adult population.

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 the use of analgesics reimbursed in France over a 10-year period through its prevalence. METHODS: A cross-sectional study repeated yearly was conducted by using data from the French reimbursement database from 2006 to 2015. Analgesics were classified according to their pharmacological potency: prevalence of use for each category and sociodemographic characteristics of patients treated were analysed. RESULTS: The annual prevalence of analgesic use was high and increased during the study period (59.8%, 253 976 users in 2015). In 2015, prevalence was always higher in women and increased with age, except for those older than 84 years. Peripheral analgesics were the most used (55.3%, 234 739 users). The prevalence of weak analgesic use decreased (21.3%, 90 257 users), mainly due to the definitive withdrawal of dextropropoxyphene in France in 2011, which was not offset by an increase in the consumption of other weak analgesics. For strong analgesics (1.2%, 5129 users), morphine was the most widely used, with a dramatic increase in oxycodone use, especially in the elderly. CONCLUSION: The prevalence of analgesic use is high: approximately 31 million adults had at least 1 analgesic reimbursed in 2015. The most widely used analgesics were peripheral analgesics, far ahead of opioid analgesics.

Patterns and profiles of methylphenidate use both in children and adults.

AIM: The aim of the present study was to characterize patterns of use of methylphenidate (MPH), a prescription stimulant medication recommended in the treatment of attention deficit hyperactivity disorder (ADHD) and of narcolepsy, in France, both in children and adults, over a 3-year period. METHODS: Using the French General Health Insurance database, limited to two areas covering approximately 4 million individuals, we made up a cohort of incident MPH users between July 2010 and June 2013. Splitting them into distinct age groups (18-24, 25-49 and ≥50 years of age for adults and <6, 6-11 and 12-17 years of age for children), we established the characteristics of these populations at MPH initiation and during follow-up according to the duration of treatment, quantities dispensed and coprescription with central nervous system (CNS) drugs. RESULTS: We included a cohort of 3534 incident users, involving 30 238 dispensings of MPH, leading to an annual rate of 29 incident users per 100 000 in 2013. Children (66% of new users) were characterized by long-term use of MPH with few comedications. The group of 25-49-year-old patients were dispensed MPH more frequently than other groups, had the highest mean dose and were more often coprescribed other CNS drugs. The ≥50 year-old group was more often coprescribed antidepressants and antiparkinsonian drugs. CONCLUSIONS: Our pharmacoepidemiological study involving incident MPH users with a large number of characteristics showed different patterns of MPH use among children and adults. The results from the 25-49-year-old group suggested that MPH might be being used for medical conditions other than ADHD or narcolepsy in adults, and that it might be subject to misuse and/or abuse.

[Interest of take-home naloxone for opioid overdose]. / Intérêt de la mise à disposition de la naloxone auprès des usagers de drogues pour le traitement d'urgence de surdosage d'opioïdes.

Over the course of these last decades, we observed a change on opioid use with the marketing of opiate maintenance treatment, an increase of opioids used for pain management and recent concerns have arisen around the use of synthetic opioid. The World Health Organization (WHO) reports around 70,000 people opioid overdose death each year. In France, according to the DRAMES program (fatalities in relation with abuse of licit or illicit drugs) of the French addictovigilance network, most of deaths are related to opioids overdose (especially methadone, following by heroin, buprenorphine and opioid used for pain management). Opioid overdose is treatable with naloxone, an opioid antagonist which rapidly reverses the effects of opioids. In recent years, a number of programs around the world have shown that it is feasible to provide naloxone to people likely to witness an opioid overdose. In 2014, the WHO published recommendations for this provision and the need to train users and their entourage in the management of opioid overdose. In this context, in July 2016, French drug agency has granted a temporary authorization for use of a naloxone nasal spray Nalscue®. Because different opioids can be used and because each opioid has specific characteristics (pharmacodynamics, pharmacokinetics, galenic form…), the risk of overdose may differ from one opioid to another and it may be necessary, depending on the clinical context, to use larger and repeated doses of naloxone.

Methylphenidate: Gender trends in adult and pediatric populations over a 7year period.

OBJECTIVE: Methylphenidate (MPH) is a prescription-stimulant medication which is authorized in France for two indications: attention-deficit hyperactivity disorder in children (aged≥6years) and narcolepsy in cases where modafinil is ineffective (for children and adults). MPH use has increased worldwide in the past 2 decades in children and adults. Different pharmacoepidemiological Europeans studies have described MPH patterns of use. To our knowledge, few pharmacoepidemiological studies have described MPH patterns of use in France. METHODS: In this context, we have performed a study on regional reimbursement database (PACA-Corse area, covering approximately 4 millions inhabitants). The first part of the study analyzed the evolution of MPH users characteristic's yearly (grouped by age and gender) over a 7year period (2005-2011). In order to better characterize patterns of MPH use in adults, a specific analyze has been performed in the second part on MPH adult users in 2011 with a gender descriptive approach. RESULTS: During the 7year period, MPH dispensing grew from 0.28 to 0.68 patient per 1000. The proportion of adult patients rose from 14.8 to 25.7% (P<0.0001), with patients mainly aged 35-49years old. Gender differences in MPH users were noted between adults and children: the proportion of girls was less important in children than in adult (in 2011, 20.7% of girls among children vs 44.9% among adults). Moreover, the proportion of girls among children increased between 2005 to 2011 (15.1% of girls in 2005 versus 20.7% in 2011). Among adults, women were prescribed more antidepressants (41.5% versus 28.2%, P=0.003) and less opiate maintenance treatments (22.4% versus 31.9%, P=0.03) than men. Finally, 11% of men and 16.4% of women were over 50years old. CONCLUSION: MPH prescription greatly increased over7years, especially in adults. Moreover, in this population, patterns of MPH use differed with gender specificities. Such findings may increase clinical attention on monitoring MPH use in adults.

[Surveillance system on drug abuse: Interest of the French national OPPIDUM program of French addictovigilance network]. / Dispositif pharmacoépidémiologique de surveillance des substances psychoactives : intérêts du programme national OPPIDUM du Réseau français d'addictovigilance.

It is important to assess drug abuse liability in 'real life' using different surveillance systems. OPPIDUM ('Observation of illegal drugs and misuse of psychotropic medications') surveillance system anonymously collects information on drug abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. The aim of this article is to demonstrate the utility of OPPIDUM system using 2015 data. OPPIDUM is a cross-sectional survey repeated each year since 1995. In 2015, 5003 patients described the modality of use of 10,159 psychoactive drugs. Among them, 77% received an opiate maintenance treatment: 68% methadone (half of them consumed capsule form) and 27% buprenorphine (39% consumed generic form). Brand-name buprenorphine is more often injected than generic buprenorphine (10% vs. 2%) and among methadone consumers 7% of methadone capsule consumers have illegally obtained methadone (vs. 9% for syrup form). The proportion of medications among psychoactive drugs injected is important (42%), with morphine representing 21% of the total psychoactive drugs injected and buprenorphine, 16%. OPPIDUM highlighted emergent behaviors of abuse with some analgesic opioids (like tramadol, oxycodone or fentanyl), pregabalin, or quetiapine. OPPIDUM highlighted variations of drugs use regarding geographic approaches or by drug dependence care centers (like in harm reduction centers). OPPIDUM clearly demonstrated that collection of valid and useful data on drug abuse is possible, these data have an interest at regional, national and international levels.

Patterns of Methylphenidate Use and Assessment of Its Abuse among the General Population and Individuals with Drug Dependence.

PURPOSE: The aim of this study was to describe the extent of methylphenidate (MPH) abuse and characterize its patterns by following several cases involving intravenous administration of crushed MPH tablets. METHODS: First, a drug reimbursement database (covering 4 million inhabitants) was explored to assess the magnitude of MPH abuse among the general population, and second, a specific study based on individuals with drug dependence was performed to describe abusers' characteristics (n = 64), patterns of abuse and clinical implications. RESULTS: From 2005 to 2011, the number of patients who were dispensed MPH at least once increased by 166%. The patients with 'deviant' patterns of MPH consumption were mainly male adults with opiate maintenance treatment reimbursements. MPH abusers had precarious living conditions. Half of them consumed MPH daily by intravenous route and reported amphetamine-like effects (cardiovascular events, weight loss, psychiatric adverse events). CONCLUSION: Given the increase of MPH use, it is important to warn the scientific community about possible MPH abuse, especially in individuals with drug dependence. This study has facilitated public health intervention and dissemination of information related to MPH abuse among health care professionals at local and national levels.

Three Complementary Approaches to Characterize Buprenorphine Misuse.

BACKGROUND: In France, buprenorphine has been available for opioid maintenance therapy since 1996 and since then its misuse has been continuously evaluated by the French health authorities. OBJECTIVES: To characterize buprenorphine misuse in Languedoc-Roussillon (LR) region, using three different approaches. METHODS: Three different data sources were analyzed : (i) spontaneous reports (NotS) of buprenorphine misuse or dependence, (ii) a specific periodic survey from specialized care centers (OPPIDUM) over 11 years (2002-2012) and (iii) a drug reimbursement database (DRB). RESULTS: A total of 209 spontaneous reports were collected. The main type of buprenorphine misuse was use by an unintended route of administration. The main complications notified were directly related to the injection of buprenorphine. NotS enabled the collection of data about severe clinical complications or new diversion phenomenon. The OPPIDUM LR survey revealed a decrease in the buprenorphine misuse indicator through the study period. The DRB analysis identified one subgroup of patients with a buprenorphine deviant behavior, characterized by a significantly greater number of dispensing episodes, pharmacies, prescribers, daily dose and switch between buprenorphine forms (princeps and generic). The DRB analysis provides data on buprenorphine diversion in the context of outpatients care. CONCLUSION: The three complementary approaches allowed us to characterize buprenorphine misuse in LR area. The three approaches are complementary because each data source provides different types of information.

[Characteristics of subjects under opiate maintenance treatment in primary care using the OPEMA data 2013]. / Caractéristiques des sujets sous traitement de substitution vus en médecine générale d'après l'enquête nationale OPEMA 2013.

AIM: The objective of the study is to describe the characteristics of subjects under opiate maintenance treatment by general practionners (GPs). METHOD: Data analysis from observatory for pharmacodependency in ambulatory medicine survey (observation des pharmacodépendances en médecine ambulatoire [OPEMA]) program in 2013 of the subjects under high dosage buprenorphine (HDB) and methadone prescribed or obtained illegally reported by GPs in France. RESULTS: Survey concerned consumers with 862, 433 and 429 of high dosage buprenorphine and respectively methadone. The average age is 39±9 years respectively, and 36±8 years; over 70% are male; 55% have paid employment and over 30% report social benefits; 9% are in temporary housing. In both groups, more than 50% have anxiety and depression; over 25% have associated somatic disorders and digestive diseases, respiratory, pain is the most common. Almost 99% use oral route; nearly 100% have a daily consumption and about 20% of the alcohol concomitantly; 24% of HDB use benzodiazepines and 18% of the methadone group (P=0.06); 33% of the population using methadone consume illicit psychoactive substances and 21% for HDB population (P<0.0001), in particular cannabis (P<0.0001). Heroin and cocaine are also consumed. CONCLUSION: The population consuming opiate maintenance treatments shows social, somatic and psychiatric vulnerability. Misuse associated forms and consumption of other psychoactive substances and illegal drugs are observed. Despite the complexity of management of these patients, general practitioners have a major role to play.

[The current aspects of the use of ecstasy/MDMA in France]. / Les aspects actuels de l'usage de l'ecstasy/MDMA en France.

Methylenedioxymethamphetamine (MDMA), the active compound of ecstasy, has been used for several years, especially by young adults to benefit of psychostimulant properties. By raising the level of neuromodulators in the synapsis, MDMA can cause psychiatric and physical injuries. After reduced supplies in 2009 (number of ecstasy seizures equal to 10 percent of those recorded in 2002), judicial authorities now observed an increased availability (a half more part of seizures in 2012 than 2010). From its "Spontaneous Notifications" data base and "deaths in connection with the abuse of medicine and substances (DRAMES)", "observation of illegal drugs and misuse of psychotropic medications" (OPPIDUM), and "observation of drug dependencies in ambulatory medicine" (OPEMA) national inquiries, the French Addictovigilance network (CEIP-A) highlighted the increasing consumption of MDMA. The way of use appeared quite unchanged: users were mainly young men between 25 and 30 years; they favored an occasional use but mainly combined other products such as alcohol, cannabis and other stimulants. Severity of the clinical cases, based on hospital care and forensic data, could be consistent with the higher amounts of MDMA measured in pills.

Use of a multi-state model in a claims database: illustration with methadone.

PURPOSE: In pharmacoepidemiology, one of the main concerns is analysis of drug exposure time. However, in real-life settings, patient's behavior is complex and characterized by drug exposure dynamics. Multi-state models allow assessing the probabilities of various patterns, instead of just continuous use and/or discontinuation. The aim of this study was to illustrate with methadone, the use of multi-state model (MSM) in a large claims database. METHODS: This study is based on the French health insurance reimbursement database. Methadone exposure is defined using four states for each period of follow-up: syrup only, capsule only, syrup-capsule and no dispensing. The model considered 12 possible transitions (including reverse transitions) from one state to another. To describe these transitions a time-homogeneous Markov model was used. RESULTS: A total of 1265 methadone users were included. When patients belonged to the syrup-capsule state, they had a 61.8% chance of moving to capsules the following month and 20.9% of moving to syrup. The probability of moving from the syrup to the non-user state was 13.6% (11.7% from capsule state to non-user state). The average length of stay was 5.9 months (CI95%: [5.5-6.4]) in capsule state, 4.9 (CI95%: [4.6-5.2]) in syrup state and 5.9 (CI95%: [5.5-6.3]) in non user state. CONCLUSION: MSM provided a good description of methadone patterns of use. It outlined behaviors which have led to a rapid spread of capsule formulation among methadone users. Therefore, it illustrates the utility of MSM for modeling multiple sequences of drug use in a large claims database.

New methadone formulation in France: results from 5 years of utilization.

BACKGROUND: In France, methadone has historically been less accessible than buprenorphine. In 2008, a dry formulation (capsule) was introduced into the market, aimed in particular to improve methadone accessibility. OBJECTIVE: To describe the impact (prevalence of use, patient profiles and compliance with requirements) of the dry methadone formulation in France. METHOD: A retrospective cohort (from 2008 to 2012) was created from the data of the French General Health Insurance System which covers 80% of the French population. For each years, all subjects affiliated to this insurance system in southeast France (about 8.5 million inhabitants) with at least two reimbursements of methadone between 1st January and 31st December were selected. RESULTS: In 2012, the proportion of capsule users was almost the same as that of syrup users (40.0% versus 43.1%; p < 0.001). The rise in the number of methadone users has followed the rise in capsule users. Over the study period, the proportion of patients using benzodiazepines or antidepressants was 6-9% (p < 0.001) higher for capsule users than for syrup users. On average over the study period, 18% of subjects had at least one concurrent issue of the two forms. CONCLUSION: The study has shown the rapid spread of the capsule formulation among methadone users. This may suggest that the capsule is well accepted by patients and the medical community. However, the monitoring of methadone-related deaths should continue because of the pharmacodynamic properties of methadone and the context of relaxed regulations concerning access to methadone maintenance treatement (MMT).

Example of an investigation of an "emergent" phenomenon in addiction vigilance: the case of methylphenidate.

Abuse of and addiction to medication are a major public health issue which is evolving fast, in particular in countries like France, one of the largest consumers of medication in Europe. As a single source of information is not generally sufficient to measure a phenomenon as difficult to apprehend as medication-related addiction, as can be seen in the case of methylphenidate, it is essential to mobilise all the tools available, here surveillance programmes developed by the French CEIP Addiction vigilance network, such as suspicious prescriptions indicating possible abuse data (OSIAP) or observatory of illegal or misused psychoactive medications (OPPIDUM), as well as the health insurance databases, and health professional sentinel networks. The latest data available on methylphenidate abuse in France suggests a stabilisation of the phenomenon, which emerged in the Provence-Alpes-Côte-d'Azur (PACA) region in southern France. It also evidences its diffusion to other regions, so that the information needs to be widely relayed, and suggests that health professionals should exercise the greatest caution in the use of this substance, and should look for early signs of its misuse.

[Use of generic high dose buprenorphine (HDB): about a qualitative survey]. / Utilisation des génériques de la buprénorphine haut dosage (BHD) : évaluation qualitative.

OBJECTIVE: Analyze the factors of the low use of buprenorphine (HDB) generic in France, studying heath care professionals' and patients' attitudes towards this substitution. METHODS: A qualitative method based on the realization of semi-directive conversations was held. 14 health care professionals and 10 patients were interviewed. RESULTS: Generic drug of HDB presents undeniable economic benefits and galenic advantages. Physicians suggest this generic at first prescription or with stabilized patients. The switch princeps/generic is more difficult with patients who diverted the product, or when they are accustomed to the brand product. Some patients prefer brand product because of its galenics, or of the perception of greater efficiency. CONCLUSION: There is a certain distrust compared to this generic. It is necessary to properly support the prescription of this drug in order to help health care professionals and patients (therapeutic education, medical information, creating a climate of trust).

Patterns of ketamine use among people with substance use disorder in France: Multisource analysis of the data from the French Addictovigilance Network.

BACKGROUND: Due to its psychoactive effects, ketamine has become a drug used for non-medical purpose. OBJECTIVES: To assess the latest trends in ketamine use among people with substance use disorder and to characterize its clinical complications using complementary health data sources of the French Addictovigilance Network. METHODS: First, we extracted all reports involving ketamine from 2012 to 2021 from the database of the OPPIDUM program (i.e., a multicentric program conducted in collaboration with hundreds of substance abuse treatment facilities that collects data on drugs used by subjects with substance use disorders). We described the reports globally and the changes from 2012 to 2021. Second, we extracted all cases involving ketamine from July 2020 to December 2022 from the French National Pharmacovigilance Database (BNPV). We identified the cases related to ketamine use among people with substance use disorder and described them. RESULTS: There was a 2.5-fold increase in the number of ketamine users with substance use disorder in the OPPIDUM program, from 35 (0.7%) subjects in 2012 to 89 (1.7%) subjects in 2021. There was an increase in the proportion of subjects who were daily users, had distress upon discontinuation, and presented addiction. There were 238 cases related to ketamine use among people with substance use disorder in the French National Pharmacovigilance Database from July 2020 to December 2022. Among them, 94 (39.5%) cases involved ketamine use disorder, 20 (8.4%) cases involved urinary tract and kidney symptoms, and 13 (5.5%) cases involved hepatobiliary symptoms. CONCLUSION: The trend observed over 10 years reflects the growth in ketamine use among people with substance use disorder, although it does not allow to estimate the rates of non-medical use of ketamine in the general population. Ketamine-induced uropathy and cholangiopathy are reported in ketamine users with substance use disorder, especially in case of repeated and/or prolonged use of high doses.

[Which psychoactives substances are found in used syringes?] / Analyse des seringues usagées : un reflet de la consommation de substances psychoactives par les usagers de drogues par voie intraveineuse ?

OBJECTIVE: The aim of this study is to analyze the residual content of used syringes. METHODS: Used syringes were collected in March 2014 at 9 sites in Marseille (automatic injection kit dispensers, streets, drug-user risk reduction centers [Centres d'accueil et d'accompagnement à la réduction de risques pour usagers de drogues [CAARUD]). Several substances (n=28) were investigated using liquid chromatography and mass spectrometry method. RESULTS: On average, 2±1 substances in each syringe were found among 254 syringes analyzed. The most detected substances were cocaine, buprenorphine, methylphenidate and cathinones (in 57 %, 56 %, 39 % and 19 % of the syringes respectively). Heroin and morphine were found in 10 % of the syringes. DISCUSSION-CONCLUSION: This study helps define the main substances consumed by injection drugs users. It highlighted differencies in used substances according to neighborhood and site of collection and thus help to adjust prevention and harm reduction strategies.

[Opioid overdose prevention and naloxone diffusion (POP program): Results of an overview conducted among addiction specialized centres]. / Prévention des surdoses opioïdes et diffusion de naloxone (programme POP) : résultats d'un état des lieux réalisé auprès des structures d'addictologie.

INTRODUCTION: In France, opioids are responsible for the majority of overdose deaths in France. The antidote naloxone is available in France in take home formulations since 2016. Addiction specialized centres are in front-line for naloxone diffusion. The objective was to provide an overview of professional practices, difficulties and needs regarding overdose prevention and naloxone diffusion in these centres of the Provence-Alpes-Côte d'Azur (PACA) region. METHODS: The POP programme "Prevention and harm reduction of opioid overdoses in PACA region" aims to improve the care of patients at risk of overdose and facilitate naloxone diffusion. The 75 addiction specialized centres of the PACA region were invited to respond to a semi-structured interview or a telephone questionnaire. Data collected included 2020 centres' activity and professionals' perceptions of overdose risk in their active file, their practices, difficulties and needs. RESULTS: Overall, 33 centres answered. Among them, 22 were dispensing naloxone with a mean of 20 kits dispensed in 2020 (min-max: 1-100). Two strategies were pointed out: systematically offering of naloxone to all opioids users or targeting people considered at risk. Several difficulties limiting naloxone diffusion were expressed: a lack of knowledge from opioids users, refusal from people not feeling concerned or refusing the injectable formulation, a lack of training of some professionals to be comfortable with the tool or reglementary or time constraints. CONCLUSION: Naloxone diffusion is incrementally getting into common practices. However barriers are persisting. On the basis of expressed difficulties and needs, information and training materials were co-designed and diffused.

[Increase of overdose and deaths related to methadone during COVID-19 epidemic in 2020]. / Augmentation des surdoses et décès en lien avec la consommation de méthadone durant la crise sanitaire liée au COVID-19 en 2020.

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. MATERIAL AND METHODS: We analyzed methadone-related overdoses which occurred in 2019 and 2020 from two sources: DRAMES program (deaths with toxicological analysis) and the French pharmacovigilance database (BNPV) (overdoses that did not lead to death). RESULTS: Data from DRAMES program in 2020 show methadone as the first drug involved in deaths as well as an increase in deaths: in number (n=230 versus n=178), in proportion (41% versus 35%) and number of deaths per 1000 exposed subjects (3.4 versus 2.8). According to BNPV, the number of overdose increased in 2020 compared to 2019 (98 versus 79; i.e., 1.2-fold increase) particularly during several target periods: first lockdown, end of lockdown/summer period and second lockdown. In 2020, a higher number of cases were observed in April (n=15) and May (n=15). Overdoses and deaths occurred in subjects enrolled in treatment programs or not (naïve subjects/occasional users who obtained methadone from street market or family/friends). Overdoses resulted from different factors: overconsumption, multiple drug use with depressants drugs or cocaine, injection, consumption for sedative, recreational purposes or voluntary drug poisoning. DISCUSSION/CONCLUSION: All these data show an increase of morbidity and mortality related to methadone during COVID-19 epidemic. This trend has been observed in other countries.