Medical prescription forms of opioid cough suppressants falsified by the patients before and after they switched from over-the-counter to prescription-only in France.

AIMS: The French Ministry of Health scheduled opioid cough suppressants as prescription-only drugs on 12 July 2017. The present study assessed the impact of this regulation on the diversion modalities of the concerned drugs and the related drug pholcodine by analysing the national OSIAP (Ordonnances Suspectes Indicateur d'Abus Possible) database. METHODS: Medical prescriptions with at least 1 mention of codeine, dextromethorphan, ethylmorphine, noscapine or pholcodine for cough suppression recorded in 2013-2019 were extracted from OSIAP. Annual mentioning rates were estimated by dividing numbers of mentions over those of prescriptions recorded the year considered. A descriptive analysis compared the characteristics of prescriptions before and after 12 July 2017. RESULTS: Overall, 832 mentions of the requested drugs were retrieved on 827 prescription forms. Codeine was the most frequent (n = 809, 8.7%) with 6 additional mentions of codeine/ethylmorphine combination, followed by dextromethorphan (n = 11, 0.1%) and pholcodine (n = 6, 0.1%). There was no mention of noscapine. Annual mentioning rates varied between 0 and 0.3% for all drugs except codeine. Codeine mentioning rates ranged between 0.3% (n = 2) and 0.7% (n = 9) before 12 July 2017 and increased to 10.1% (n = 61) thereafter in 2017, 16.1% (n = 314) in 2018, and 19.8% (n = 414) in 2019. The profile of subjects evolved accordingly with an increased male/female ratio (10.0 vs. 1.5 before) and decreased age (23 vs. 40 y before, P < .001). DISCUSSION: The sharp increase of recourse to falsified prescription forms indicates that codeine diversion continues despite restricted access, whereas the other drugs studied do not seem to have been impacted.

Online SPE UPLC-MS/MS method for the simultaneous determination of 33 psychoactive drugs from swab-collected human oral fluid samples.

Oral fluid is easy and safe to collect and allows the detection of drugs of abuse after local exposure by oral, smoked, and/or inhaled intake, or systemic exposure. A routine online solid-phase extraction UPLC-MS/MS method was developed for the simultaneous determination of 33 psychoactive drugs in oral fluid. The selected drugs were fourteen fentanyl analogs and nineteen other abused psychoactive compounds, including classical narcotics, which were analyzed in a run of 10 min. Limits of detection and of quantification ranged from 0.02 to 1 ng/mL and from 0.02 to 5 ng/mL depending on the analyte, respectively. Matrix effect was in the range - 17 to + 15.7% for all analytes having a deuterated analog. Accuracy ranged from 82.7 to 113.4% and precision CV was at worst of 18.6%. Carryover was below 0.8% for all analytes. Recovery from FLOQSwabs™ showed high variability between analytes with THC, D2FF, 4-ANPP, ocfentanil, and valerylfentanyl being recovered below 40%. A stability study performed over 2 weeks on collecting devices loaded with artificial oral fluid showed huge variation between analytes with morphine, BZE, and norfentanyl being the more stable. Storage at 4 °C allowed drug detection for 1 week except for THC and remifentanil. The method was successfully applied to the detection of abused psychoactive compounds in oral fluid samples from 6 patients admitted to an addiction department.

Acute effects of synthetic cannabinoids: Update 2015.

BACKGROUND: Cannabis is the most widely used illicit drug in the United States and Europe. In recent years, a range of new substances with cannabis-like effects-known as synthetic cannabinoids (SCs)-have suddenly burst on the drug scene. However, there is limited information about the clinical hazards linked to the use of these emerging substances. This review summarizes the literature to date relating the health effects of SCs. METHOD: A systematic literature review of original case studies was performed using PubMed and Web of Science (January 1980-July 2015). Only articles in which a drug screening was reported were included in this review. RESULTS: Forty-six articles meeting the inclusion criteria were included in this review, reporting data on 114 patients who went to hospital emergency departments after exposure to SCs. The majority of patients were adolescent or young adult males (14-25 years; 24.5 ± 10.1 years). The most common route of administration was smoking. The SCs most involved were John William Huffman (JWH) derivatives, followed by XRL-11, ADB-PINACA, AM-2201, MAM-2201, and 5F-PB-22. This analysis showed that the use of these substances may cause minor and moderate side effects similar to those of cannabis intoxication, including tachycardia, nausea, somnolence, hallucinations, paranoia, xerostomia, and injected conjunctivae among others. However, atypical cannabis intoxication effects and worse complications (such as renal injuries, aggressiveness, cerebral ischemia, myocardial infarction, etc.) were also observed, which led to a significant morbidity were also observed. Some SCs were highlighted as being involved in 24 cases of deaths. CONCLUSIONS: In this review, the nature and frequency of the signs and symptoms of SC poisoning were estimated in order to inform health professionals about the health risks of these new and emerging substances.

[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.

[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.

Are Physicians Safely Prescribing Opioids for Chronic Noncancer Pain? A Systematic Review of Current Evidence.

BACKGROUND: With rising prescription of opioid medications for chronic noncancer pain (CNCP) in the past years, opioid abuse and overdose deaths have increased in parallel. To ensure adequate treatment outcomes and reduce the risks linked with the chronic use of opioids, practitioner's adherence to treatment guidelines is essential. This study summarizes published recommendations about the strategies to reduce the risks associated with the chronic use of opioids and evaluates the adherence of physicians to these recommendations. METHOD: A systematic literature search was undertaken in May 2014 using major databases. Studies were included if they examined the adherence of practitioners with at least one form of opioid risk reduction strategy. Benchmark guidelines cited in these studies were also reviewed. RESULTS: The search yielded 683 records, 14 of which were found to evaluate adherence of physicians to opioid risk reduction strategies. Nine benchmark guidelines were found. Almost all physicians consider opioid therapy only when other safer approaches have failed and do not prescribe opioids at doses greater than 200 mg/day of morphine equivalent. Unfortunately, less than 50% assess pain intensity using a pain scale; they often consider transdermal fentanyl safe for opioid-naïve patients and fail to discontinue opioids if they were ineffective in relieving patients' pain. CONCLUSIONS: Substantial practice and knowledge gaps were identified, including the use of pain scales and prescription of transdermal fentanyl in opioid-naïve patients, which have important implications for patient's safety. Guidelines more practical to physicians' settings and further education of physicians are warranted.

Signal identification in addictovigilance: the functioning of the French system.

The French addictovigilance network (addictovigilance: surveillance of addiction), composed of 13 Addictovigilance Centres, was set up in 1990 in order to achieve reliable surveillance and evaluation of abuse and dependence cases due to psychoactive substances (alcohol and tobacco excepted). The detection of safety signals is one of the roles of the addictovigilance centres. Signals from spontaneous reports need to be analyzed before further communication. In addictovigilance, signals may be linked to adverse effects (deaths, pathological signs), to products (new psychoactive substances with potentially dangerous effects) or to practices (new administration routes, new contexts of use). These signals are provided by numerous partners among whom the addictovigilance network has to raise awareness about information that may possibly be an alert signal. The watchful attitude of all partners will make it possible that signals will be, after analyze, considered as true alerts. The addictovigilance network collects data, assess the potential for addiction of psychoactive drugs to provide information on the risk of addiction and give opinions for public health decisions (harm reduction or prevention programs, psychoactive substances control, health alerts).

[Counterfeit and Falsified Drugs: an Overview]. / Trafic de faux médicaments : panorama 2014.

If the traffic of fake medicines may represent an economic threat for the pharmaceutical industry, it can also be responsible of safety concerns for patients. Despite fake drugs represent a real threat for public health, the intended punishments are until now only based on intellectual property rights. Estimated to generate more than 55 billion euros per year, the traffic of falsified drugs varies from a country to another one. Indeed, the proportion of falsified drugs ranges from 1% in industrialized countries with a regulated and controlled distribution system to 60% of medicines in some developing countries. Currently, the measures developed to limit this traffic concern five main areas: legislation / regulation, cooperation, enforcement, technology and communication. Communication actions should be performed to inform health professionals as the populations about the risks of using drugs purchased outside the legal drug market.

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.

Necrosis of the intranasal structures and soft palate as a result of heroin snorting: a case series.

BACKGROUND: The link between nasal inhalation of cocaine and nasal and palatal necrosis is well documented. In contrast, few data are available concerning nasal mucosa necrosis related to heroin snorting. The authors report here the retrospective analysis of 24 cases of orofacial lesions in patients with nasal heroin usage, collected between 2006 and 2012. CASES: The cases concern 17 males and 7 females (median age 29.5 (range: 24-42)) with chronic consumption of intranasal heroin (from 2 months to more than 10 years). Six patients had a history of cocaine abuse. The median daily amount of heroin consumption was 5 g (range: 0.5-10). The complications were nasal perforation (11 cases), nasal ulceration or erythema (5 cases), nasal septum necrosis (5 cases), pharyngeal ulceration (3 cases), and palate damages (5 cases). The most common clinical signs and symptoms were nasal pain, purulent sputum, dysphagia, and rhinitis. Maintenance therapy with methadone (19 cases) or buprenorphine (3 cases) was initiated. In 8 cases, the injury improved. DISCUSSION: The potential of heroin to induce destructive orofacial lesions should be considered when nasal damages are observed in patients with drug abuse. A multidisciplinary approach seems to be the most effective means of managing such patients.

Non-medical use of baclofen: A case series and review of the literature.

BACKGROUND: Baclofen is widely used for spastic disorders and, most recently, for addictive disorders. The first signals of baclofen abuse occurred in the last decade. This study aims to assess the motives, diversion sources, and routes of administration associated with the non-medical use of baclofen and examine health problems related to the non-medical use of baclofen. METHODS: Spontaneous reports of baclofen abuse reported to the addictovigilance centre of East France were analysed. A literature search was conducted using PubMed®, Web of Sciences®, and Google Scholar® databases. Both investigations were performed in February 2021 without a time limit. RESULTS: Forty-six cases were analysed (33 from the literature review and 13 from the addictovigilance base). Baclofen's non-medical use mainly affected male subjects with addictive history, but issues of primary abuse in subjects without any substance abuse history were also observed. Euphoria search was the most common reason for misuse. The route of administration included oral, snorting, and sublingual use. Some cases involving illegal sources were also observed. Most patients misusing baclofen presented severe complications, mainly represented by neurological and respiratory disturbances. Physical and psychological dependence on baclofen was observed in three persons. CONCLUSIONS: Although baclofen abuse remains relatively infrequent or (most likely) underestimated, this study helped confirm baclofen's intrinsic abuse potential and make visible the baclofen-abuse-related health visible harms. Careful consideration and benefit-risk analysis should be employed when prescribing baclofen, and emergency departments should be aware of baclofen dangers in abuse situations.

[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.

Alprazolam misuse: Analysis of French Addictovigilance Network data from 2011 to 2020.

OBJECTIVES: Alprazolam, a high-potency and short-acting anxiolytic benzodiazepine, is one of the most misused benzodiazepines in France. In the context of various reports on alprazolam misuse during the COVID-19 pandemic, the objective of this study was to assess alprazolam abuse potential by analyzing French addictovigilance and international data. METHODS: Data collected from 2011 to 2020 using the following epidemiological tools of the French Addictovigilance Network were analyzed: spontaneous reports (SRs), OPPIDUM (addiction care center data), OSIAP (falsified prescriptions), DRAMES (substance-related deaths), and chemical submission surveys. Moreover, the VigiBase™ database was analyzed to evaluate alprazolam abuse liability worldwide. RESULTS: During the study period, 675 SRs concerning alprazolam misuse were recorded (sex ratio: Ì´1; median age: 39 years). The desired effects were intensification of the therapeutic anxiolytic effect, euphoric effect, and management of substance withdrawal. Alprazolam was the third and first benzodiazepine listed in OPPIDUM and OSIAP surveys. Analysis of the SR and OPPIDUM data showed a recent increase in the alprazolam-opioid combination. In DRAMES data, alprazolam was directly linked to 11 deaths (associated with opioids in 10/11). VigiBase™ data analysis highlighted that France was the third country with the most cases of alprazolam misuse. The disproportionality analysis showed that in France, alprazolam was associated with higher risk of misuse and dependence compared with other benzodiazepines: reporting odds ratio=1.43, (95% CI: 1.04-1.95) and=1.97 (95% CI:1.50-2.59), respectively. CONCLUSIONS: This study highlighted an increase in various signals of alprazolam abuse in France, and an increased use of the alprazolam-opioid combination that was also linked to most of the recorded alprazolam-linked deaths. These signals have been reported also in the international literature, and should be thoroughly investigated.

Multiplex detection of 14 fentanyl analogues and U-47700 in biological samples: Application to a panel of French hospitalized patients.

Synthetic opioids (SO) associated with the recent alarming increase of deaths and intoxications in United States of America and Europe are not detected by the usual first-line opiates drug screening assays. We developed a liquid chromatography tandem mass spectrometry analytical method for the multiplex detection of 14 fentanyl analogues (2-furanylfentanyl, 4-ANPP, 4-methoxybutyrylfentanyl, acrylfentanyl, alfentanil, carfentanil, despropionyl-2-fluorofentanyl, fentanyl, methoxyacetylfentanyl, norfentanyl, ocfentanil, remifentanil, sufentanil and valerylfentanyl) and U-47700 in whole blood and urine samples. The method was validated according to the requirements of ISO 15189. A simple and fast liquid-liquid extraction (LLE) with De-Tox Tube-A was performed leading to better recovery of molecules in urine than in blood samples. Depending on the compound, the limits of detection (LODs) ranged from 0.01 to 0.10 ng/mL and from 0.02 to 0.05 ng/mL in whole blood and urine, respectively. Calibration curves were linear in the range 0.5-50.0 ng/mL and the limit of quantification (LOQ) ranged from 0.10 to 0.40 ng/mL in blood. Internal quality controls at 1 and 40 ng/mL showed intra-day and between-day precision and accuracy bias below 10% in urine and 15% in blood. The method was applied to the screening of 211 urine samples from patients admitted in emergency or addiction departments. The presence of legal fentanyl analogues in 5 urine samples was justified by their therapeutic use as analgesics. Only one patient was concerned by fentanyl misuse and addiction whereas no illegal SO was detected. This study is not in favor of a huge misuse of SO in the Lorraine region.

Addictovigilance contribution during COVID-19 epidemic and lockdown in France.

Addictovigilance is a safety monitoring targeted at substances with potential for abuse and dependence. This vigilance was involved during the period of COVID-19 epidemic due to the significant changes in access to drugs and psychological disruption caused by the pandemic and lockdown. This article aims to present the different steps implemented by the French Addictovigilance network in collaboration with the French Health authorities from March to May 2020, including monitoring of potential harmful events, and scientific communication. The first events were identified through the continuity of the networking between the French addictovigilance centres and their partners: community pharmacies, general practitioners, specialized structures and emergency wards. As soon as the lockdown began, first cases of overdoses (lethal or not) were reported with opioids, mainly with methadone, and other opioids (heroin, oxycodone, tramadol or antitussive codeine). Lockdown-related noteworthy events consisted in clinical cases or other relevant information for which lockdown clearly played an important role: among the many substances identified at least once, pregabalin, benzodiazepines, cannabis, cocaine and nitrous oxide were the most significant in terms of prevalence, seriousness or particularly specific to the lockdown context. Despite significant decrease in the activity and travel limited to vital needs, community pharmacies continued to identify falsified prescriptions in this period, highlighting an increase in suspicious requests for pregabalin, codeine and tramadol. In parallel, the French addictovigilance network continued its communications efforts in the period, issuing a newsletter on tramadol, a press release on methadone and naloxone, and participating in the COVID-19 frequently asked questions (FAQs) of the French Society of Pharmacology and Therapeutic website (https://sfpt-fr.org/covid19). COVID-19 epidemic has been an important challenge for addictovigilance, and has proved that this monitoring is highly essential for alerting health professionals and health authorities to points of vigilance in the field of psychoactive substances.

[French trends in the misuse of Fentanyl: From 2010 to 2015]. / Le mésusage du fentanyl en France : 2010 à 2015.

OBJECTIVES: The aim of this study was to evaluate the French use, misuse and abuse/dependence of non-injectable forms of fentanyl (transdermal and transmucosal fentanyl formulations). METHODS: Problematic use of transdermal and transmucosal fentanyl formulations was evaluated using an approach combining multiple sources of information: (1) spontaneous notifications recorded during 6 years (2010-2015) for transdermal fentanyl form and 3 years for transmucosal fentanyl forms and (2) data from annual epidemiological systematic surveys conducted by the French Addictovigilance Network during 6 years (2010-2015). RESULTS: In all, 147 cases were notified for transdermal fentanyl formulation and 109 cases for transmucosal fentanyl formulations. According to the galenic formulation, analysis of these cases emphasizes different profiles: for transdermal fentanyl formulation, two consumption profiles: 1/mainly for analgesic effects (74 %): women (61 %), 47 years, with addictive and/or psychiatric history (46 %), treated for chronic non-cancer related pain (93 %), 2/seeking positive psychic effects other than analgesia (26 %): men (82 %), 32 years, with addictive and/or psychiatric history (87 %) and having obtained the fentanyl patch illegally (60 %) for non-medical use. For transmucosal fentanyl formulations, only one consumption profile was observed: women (52 %), 48 years, with addictive (24 %) and/or psychiatric history (28 %), off label indication (72 %) (indications for non-cancer pain and/or no or insufficient opioid background treatment). The misuse of transmucosal fentanyl formulations implies a high risk of adverse effects: those already known of opioid-based drugs, sometimes lethal (withdrawal syndrome, respiratory and central nervous system depression…) but also serious reactions at the application site (buccal or nasal). For the transdermal fentanyl formulation, 27 cases (18 %) of involuntary intoxication were observed, of which 25 were serious. Nineteen deaths involving both forms of fentanyl have been reported (2 for the transmucosal formulations and 17 for the transdermal formulation). CONCLUSION: Our results report significant and worrying misuse of transmucosal fentanyl formulations with wide off-label use and also primary dependence on fentanyl, regardless of galenic formulation, in patients treated for chronic non cancer pain. Given the significant risks of fentanyl, it is necessary to continue the monitoring of misuse, in particular, thanks to the activities of the French Addictovigilance network allowing a multisource approach and who provides information concerning cases of abuse, misuse and dependence.

[Identification of abuse/dependence cases by the French addictovigilance network (FAN): A pilot study of the addictovigilance center and the psychotherapeutic center of Nancy (France)]. / Identification de cas d'abus/dépendance par le réseau français d'addictovigilance : une étude pilote du CEIP-A et du Centre psychothérapique de Nancy.

OBJECTIVES: France is the only European country with a dedicated addictovigilance network (French addictovigilance network [FAN]). However, the reporting of cases of abuse/dependence is insufficient. In an attempt to overcome this under-reporting, data from the medical information systems program (PMSI) is regularly used to identify cases. Since addictions are frequently associated with psychiatric comorbidities, a pilot study was conducted for the first time in a psychiatric hospital. It aims, through a PMSI request, to identify the sociodemographic characteristics and psychiatric diagnoses of patients consuming psychoactive substances (PAS) and the PAS types consumed. METHODS: This is a retrospective observational study conducted over a nine-month period at the psychotherapeutic center of Nancy (CPN). The codes used for the PMSI request are those of the international classification of diseases, tenth revision (ICD-10), codes F10 to F19 that characterize mental and behavioral disorders associated with the use of PAS. Cases presenting the four criteria necessary for an addictovigilance notification: (1) identified notifier, (2) identified patient, (3) known consumed product (s) and (4) presence of an effect related to the abuse/dependence of PAS; were retained and analyzed. RESULTS: On an initial number of 252 cases, 82 cases of abuse/dependence were retained. The selected sample is predominantly male (67%). Cannabis (29%) and heroin (15%) are the most common illicit PAS. Regarding drugs, the consumption of benzodiazepines, a predominantly female phenomenon, is observed in 34% of subjects. Sixty-four per cent of the subjects were diagnosed "disorders related to the use of PAS", 14% as neurotic disorders, 9% as schizophrenia and 5% as of the mood disorders. CONCLUSION: This study identified a significant number of potentially reportable cases to the French Addictovigilance Network and demonstrated the interest of investigating cases of abuse/dependence in a psychiatric hospital.

Ephenidine, diphenidine, and methoxphenidine complications reported to the French Addictovigilance Network.

Ephenidine, diphenidine, and methoxphenidine belong to the family of diarylethylamines that are psychoactive substances derived from lefetamine (N, N-di-methyl-1,2-diphenylethylamine, also called L-SPA). These dissociative anesthetic compounds act as potent and selective N-methyl-d-aspartate receptor antagonists and were recently classified as narcotic drugs in France. The available data suggest a significant risk of psychic and somatic complications. To obtain more information, this retrospective study analyzed all spontaneous notifications of serious cases of ephenidine, diphenidine, and methoxphenidine abuse collected by the French Addictovigilance Network from 2012 to 2016 and classified them as proven, probable, and possible. For each case, age, sex, concomitantly ingested substances, pattern of abuse of psychoactive drugs, and related complications (scored using the poisoning severity score) were collected. Eighteen cases were identified (one in 2013, five in 2015, and 12 in 2016) in 16 men (median age: 31.5 years [IQR 25-75% 27-34]). Ephenidine, diphenidine, and methoxphenidine were involved in four, seven, and 11 cases, respectively. No case was considered proven, 16 cases were considered possible, and two probable due to polysubstance abuse (co-ingestion of other new psychoactive substances). The reported clinical complications were minor in five cases, moderate in six cases, and serious in four cases, and included psychiatric, neurologic, and cardiovascular problems. This analysis indicates that the number of reported cases progressively increased from 2012 to 2016 and mainly concerned methoxphenidine. The addictive potential of these substances seems highly probable; but further investigations are needed to limit their harmful effects.

Opioid substitution therapy or hidden opioids are a minefield for nalmefene: an atypical case series of 11 patients in Lorraine.

Opioid antagonists such as naltrexone and nalmefene are used in drug therapy for alcoholism. Nalmefene, approved in Europe in February 2013 for the reduction of alcohol consumption, is used in patients with alcohol dependence. We report 11 cases of opioid withdrawal syndrome after a single dose of nalmefene in patients usually treated with methadone, buprenorphine, but also with fentanyl or loperamide. Nalmefene is both a partial agonist and an antagonist of opioid receptors. Regarding to its opioid antagonist activity, nalmefene is contraindicated in patients with an opioid treatment. Therefore, when prescribing or delivering nalmefene, healthcare professionals need to be vigilant about any type of opioid exposure, even masked or hidden, to avoid these potential life-threatening syndromes.