Emilie Jouanjus

Baclofen for alcohol dependence in France: incidence of treated patients and prescription patterns--a cohort study.

Recently, baclofen has been widely promoted for treatment of alcohol dependence in France. Our aim was firstly to describe the incidence of patients newly treated with baclofen for alcohol dependence in France from 2007 to 2011, and secondly to describe baclofen prescription patterns and prescribers. A retrospective cohort study of patients newly treated with baclofen was conducted using the Echantillon Généraliste des Bénéficiaires database (EGB). Patients with a first dispensation of baclofen between 01/01/2007 and 31/12/2011, followed by a second in the next 120 days, were included. Patients were considered treated with baclofen for neurological conditions if at least one of the following conditions was found to be true: (1) presence of a neurological condition for which baclofen could be prescribed, (2) dispensation of dantrolene, another anti-spastic drug, or (3) hospitalization for a neurological condition for which baclofen could be prescribed. We assumed that all the remaining patients were treated for alcohol dependence. During the 5-year period, 676 patients were incident users. While the annual incidence rate of patients newly treated with baclofen for neurological conditions remained stable, the annual incidence rate of patients newly treated with baclofen for alcohol dependence increased by a factor of 2.9 between 2007 (0.09/1000 person-years) and 2011 (0.26/1000 person-years). In the alcohol dependence group, median duration of baclofen treatment was 143.5 [74.0; 377.0] days; median daily dose was 24.4 [14.8; 39.5] mg. This study demonstrated the rapidly increasing use of baclofen in France for treatment of alcohol dependence.

Disproportionality Analysis for the Assessment of Abuse and Dependence Potential of Pregabalin in the French Pharmacovigilance Database

Background and ObjectivePregabalin abuse and dependence has been increasingly described; however, it is not described in France. Our study aimed to investigate the abuse and dependence potential of pregabalin by a disproportionality analysis, in the French Pharmacovigilance Database (FPVD), in comparison with amitriptyline and clonazepam.MethodsWe performed a case/noncase study in the FPVD. Between January, 1 2010 and December, 31 2015, we identified cases of abuse and or dependence (excluding isolated withdrawal syndromes) using MedDRA (Medical Dictionary for Regular Activities) terms. Exposure to pregabalin was defined as the mention of pregabalin in the report. Clonazepam was used as positive control and amitriptyline as negative control.ResultsAmong the 184,310 reports in the database, 521 were abuse or dependence cases. Exposure to pregabalin was found in eight (1.5xa0%) of them. We did not find any significant association between exposure to pregabalin and drug abuse or dependence: reporting odds ratio (ROR)xa0=xa01.1 95xa0% confidence interval (CI) (0.6–2.3). ROR for clonazepam was 5.7 95xa0% CI (3.5–9.2). No case of an amitriptyline-related abuse or dependence was recorded in the FPVD.ConclusionsThe first cases of pregabalin-related abuse or dependence reported in France occurred later than in other European countries, since none had been described before 2010. This analysis in the FPVD did not find a higher proportion of abuse/dependence with pregabalin in comparison with other drugs. Considering evidence of pregabalin abuse worldwide, this analysis underlines the limitations of spontaneous reporting system in the field of addictovigilance.

What is the Current Knowledge About the Cardiovascular Risk for Users of Cannabis-Based Products? A Systematic Review

Purpose of ReviewThe purpose of the study was to examine the published evidence on the cardiovascular risk related to the use of cannabis-based products by performing a systematic review of recent literature.Recent FindingsThe World Health Organization (WHO) emphasizes that cannabis use represents a risky behavior as it may lead to many adverse effects, and in particular, cardiovascular effects.SummaryA systematic review of articles published between January 1, 2011 and May 31, 2016 was performed in agreement with the PRISMA statement. Articles presenting data on humans exposed to cannabis-based products and suffering from any cardiovascular condition were eligible for inclusion. The inclusion process was based on a search algorithm and performed in a blinded standardized manner. Overall, 826 articles were found in the literature search, 115 of which remained after performing the inclusion procedure. These were 81 case reports, 29 observational studies, 3 clinical trials, and 2 experimental studies. A total of 116 individuals was the subject of case reports. The mean age was 31xa0years (95%CIxa0=xa029–34), and patients were more frequently men (81.9%) than women (18.1%). They mainly suffered from ischemic strokes or myocardial infarctions. Data provided by the 29 included observational studies evidenced an association between exposure to cannabis-based products and cardiovascular disease. Currently, this evidence is stronger for ischemic strokes than for any other cardiovascular diseases. While the data are limited, there is some suggestion that cannabis use may have negative cardiovascular consequences, particularly at large doses.

Pregabalin use disorder and secondary nicotine dependence in a woman with no substance abuse history.

This is an addictovigilance report of a pregabalin use disorder case in a young female patient who secondarily presented a tobacco use disorder after smoking initiation combined with pregabalin intake. Pregabalin was first prescribed for anxiety. Concomitant use of pregabalin with tobacco led to a synergic effect of both substances. She presented a craving behavior for pregabalin, with a tolerance phenomenon and a withdrawal syndrome between pregabaline intakes. The patient had a history of depressive disorder, personality disorder and anorexia, but never had any history of substance use disorder. This case report is noteworthy for 3 reasons: 1: this is one of the first report of pregabalin use disorder in a patient without any substance abuse disorder (licit or illicit), with the exception of a personal vulnerability factors to substance abuse; 2: the patient presented characteristics of pregabalin use disorder at usual dose (below 300mg per day), with drug-seeking behavior, tolerance phenomenon and intense craving with these moderate doses; 3: concomitant use of pregabalin with tobacco led to a synergic effect of both substances.

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.

Comment on: "Social Media Mining for Toxicovigilance: Automatic Monitoring of Prescription Medication Abuse from Twitter"

We read with great interest the article entitled ‘‘Social Media Mining for Toxicovigilance: Automatic Monitoring of Prescription Medication Abuse from Twitter’’ by Sarker and colleagues, published in a recent issue of Drug Safety [1]. It is an interesting research article dealing with the problem of monitoring abuse and addiction with prescription drugs in the real-life context. Sarker et al. are right to point out the crucial need for discovering new monitoring sources and methods to identify and better characterize the patterns of use of drugs with an abuse potential and the complications related to this use. This is indeed a critical point in the field of drug abuse and addiction as the knowledge on this topic is solely based on the collection of abuse/addiction cases reported by health professionals, published as case reports or case series, or reported to pharmacovigilance systems [2, 3]. Unfortunately, the high proportion of unreported cases limits these systems [4]. Therefore, spontaneous reporting systems must not be the only source of data [5] and need to be completed, as has been done in a few countries. For example, in the US, several complementary monitoring systems have been developed to survey the harmful consequences of drugs with an abuse potential [6, 7]. In France, the national surveillance system relies on the crossing of multiple data sources, including several original pharmacoepidemiological programs that have been specifically set up to complement the information provided by spontaneous notification and to improve the assessment of psychotropic medication misuse [8, 9]. Computerized data coming from the hospital database, or even the national reimbursement system database, are also explored [10, 11]. Combined with pharmacological data, all of these are useful for identifying addiction signals and launch alerts. Sarker et al. propose to explore the data collected by Twitter to raise data about prescription medication abuse. Furthermore, they provide a standardized method to automatically detect these data for future research. Nowadays, surveillance of the Internet seems essential as the Internet provides considerable information on the use of psychoactive substances. For example, online discussions have been explored to characterize the modalities of administration and the effects described by users of various licit or illicit psychoactive substances [12, 13]. As Twitter is a very popular social media platform, it appears to be a valuable data source to explore for addictovigilance purposes. This letter refers to the article available at doi:10.1007/s40264-0150379-4.

Adverse Drug Reaction Reports Received Through the Mobile App, VigiBIP®: A Comparison with Classical Methods of Reporting

IntroductionThe use of mobile apps is increasing in medicine. In pharmacovigilance, mobile apps may help to increase adverse drug reaction reporting and improve the communication of safety issues. The Toulouse University Pharmacovigilance Center has developed VigiBIP®, a free smartphone app available on Android and Apple stores, for reporting adverse drug reactions and requesting drug safety information.ObjectiveThe present study was performed to compare the main characteristics of spontaneous adverse drug reaction reports received through VigiBIP® with classical methods of reporting (phone, e-mail, fax, letter, website) during 25xa0months (2015–17).MethodsUsing the Chi squared test, we compared the type of reporter, adverse drug reaction seriousness, drugs involved and reported ADRs using VigiBIP® and classical methods of reportingResultsA total of 4102 reports were received by the Toulouse University Pharmacovigilance Center, including 4.7% through VigiBip®. Patients’ reports were significantly more frequent with VigiBip® (6.7%) than with classical methods (3.4%) [pxa0=xa00.01]. Reported adverse drug reactions and involved drugs differed according to the method of reporting used.ConclusionOur study shows that a mobile app is an additional tool used in pharmacovigilance. Types of reporters and adverse drug reactions in VigiBIP were different to those seen in classical methods of reporting.

Early signal of diverted use of tropicamide eye drops in France

AIMSnTropicamide is a mydriatic drug used as eye-drops for diagnostic or therapeutic purposes. From 2013, a diverted use by intravenous route has been suspected in Eastern Europe in opioids users. To date, no signal of misuse has been identified in France. The aims of this study were to investigate any early signals of a diverted use of tropicamide eye drops and to collect information regarding motives for the misuse and tropicamide-induced effects.nnnMETHODSnInformation was obtained at three levels: (1) at regional level (Midi-Pyrénées area), from reimbursement data and pharmacists reports on suspicious requests; (2) at national level: from reimbursement data and prescriptions suggesting possible abuse from the OSIAP (Ordonnances Suspectes, Indicateur dAbus Possible) survey; and (3) at international level: from VigiBase® reports and Web sources. Beta-blocker eye-drops were used as comparators.nnnRESULTSnIn France, in 2014-2015, 17 (0.91%, 95% CI [0.53-1.46%]) falsified prescriptions involving tropicamide were identified in the OSIAP survey (compared with 0%, 95% CI [0-0.19%] for beta-blockers). Moreover, 37 other suspicious prescriptions were presented in 2015 (notified in 2016). In Midi-Pyrénées, seven patients aged 35-49 were reimbursed for 19-45 vials of 10xa0ml, in a year. Since September 2014, the regional Addictovigilance Centre has received 91 notifications of suspicious requests to obtain tropicamide. In VigiBase® , two cases were identified but none in France. An increased interest in tropicamide-related Internet searches was observed from Russia and Ukraine.nnnCONCLUSIONSnThese results represent the first early warnings of a tropicamide diverted use in France. Tropicamide abusers would seek euphoria or hallucinations. The high doses involved in intravenous administration could lead to serious complications.

Detecting the diverted use of psychoactive drugs by adolescents and young adults: A pilot study

The increasing trend of diversion of nonprescription drugs (NPDs) by adolescents or young adults is worrying. We implemented this pilot study before a national investigation to identify requests for suspected recreational use of psychoactive drugs made by young subjects to community pharmacies.

Identification of Somatic Disorders Related to Psychoactive Drug Use from an Inpatient Database in a French University Hospital

Background and ObjectiveStudies have explored hospital records to identify serious complications related to use of psychoactive drugs, but this approach is time consuming with a high rate of false positives. We propose a method to improve the detection of these somatic complications from an inpatient database.MethodsHospitalisations in Toulouse University Hospital (France) between 1 July and 31 December 2013 with at least one International Classification of Diseases, Tenth Edition (ICD-10) code related to possible abuse/addiction (F11–F19: “mental and behavioural disorder due to psychoactive substance use”, T40–T43: “poisoning”, or X61–X62: “self-poisoning”) and at least another ICD-10 code unrelated to abuse/addiction were extracted. Hospital discharge summaries (HDS) were reviewed using two strategies: in Strategy 1, all HDS were reviewed, whereas in Strategy 2, associated ICD-10 codes unrelated to abuse/addiction were firstly assessed to preselect some HDS. Positive predictive values (PPVs) were calculated to evaluate their performance.ResultsWith Strategy 1, we found 58 psychoactive drug-related somatic complications among the 578 hospitalisations extracted (PPVu2009=u200910.0%), including three cases spontaneously reported to the French Addictovigilance Network. Strategy 2 retained 94.8% of the hospitalisations identified with Strategy 1, while the number of reviewed HDS was reduced by half (PPVu2009=u200920.1%). Cannabis (56.9%), cocaine (27.6%) and prescription opioids (22.4%) were mainly involved. Complications mainly corresponded to nervous (25.9%) and respiratory and circulatory (22.4%) system disorders.ConclusionsCombining extraction of ICD-10 codes and a focused review of a preselection of relevant hospitalisations appears to be efficient and time-saving. This method should be applied in other hospital settings before considering the exploration of inpatient data on a wider scale.