Assessing the 2004-2018 fentanyl misusing issues reported to an international range of adverse reporting systems

© 2019 Schifano, Chiappini, Corkery and Guirguis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Submitted 2 October 2018, Accepted 14 January 2019, published 1 February 2019.Objective: A recent, global, increase in the use of opioids including the prescribing, highly potent, fentanyl has been recorded. Due its current popularity and the potential lethal consequences of its intake, we aimed here at analyzing the fentanyl misuse, abuse, dependence and withdrawal-related adverse drug reactions (ADRs) identified within the European Medicines Agency (EMA), the United Kingdom Yellow Card Scheme (YCS), and the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) databases. Methods: Descriptive analysis of both ADRs and related cases. Results: The analysis of fentanyl-related misuse, abuse, dependence and withdrawal cases reported during years 2004-2018 to the EMA, the YCS, and the FAERS showed increasing levels overtime, specifically, EMA-related data presented two peaks (e.g., in 2008 and 2015), whilst the FAERS dataset was characterized by a dramatic increase of the ADRs collected over the last 18 months, and particularly from 2016. Some 127,313 ADRs (referring to n = 6,161 patients/single cases) related to fentanyl's misuse/abuse/dependence/withdrawal issues were reported to EMA, with 14,287 being judged by the reporter as "suspect." The most represented ADRs were: "drug dependence "(76.87%), "intentional product misuse" (13.06%), and "drug abuse" (7.45%). Most cases involved adult males and the concomitant use of other prescribing/illicit drugs. A range of idiosyncratic (i.e., ingestion/injection of transdermal patches' fentanyl) and very high-dosage intake cases were here identified. Significant numbers of cases required either a prolonged hospitalization (192/559 = 34.35%) or resulted in death (185/559 = 33.09%). Within the same time frame, YCS collected some 3,566 misuse/abuse/dependence/withdrawal ADRs, corresponding to 1,165 single patients/cases, with those most frequently reported being "withdrawal," "intentional product misuse," and "overdose" ADRs. Finally, FAERS identified a total of 19,145 misuse/abuse/dependence/withdrawal-related cases, being "overdose," withdrawal, and "drug use disorder/drug abuse/drug diversion" the most represented ADRs (respectively, 43.11, 20.80, and 20.29%). Conclusion: Fentanyl abuse may be considered a public health issue with significant implications for clinical practice. Spontaneous pharmacovigilance reporting systems should be considered for mapping new trends of drug abuse.Peer reviewe

Over 1200 drugs-related deaths and 190,000 opiate-user-years of follow-up : relative risks by sex and age-group

Heroin users/injectors' risk of drugs-related death by sex and current age is weakly estimated both in individual cohorts of under 1000 clients, 5000 person-years or 50 drugs-related deaths and when using cross-sectional data. A workshop in Cambridge analysed six cohorts who were recruited according to a common European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) protocol from drug treatment agencies in Barcelona, Denmark, Dublin, Lisbon, Rome and Vienna in the 1990s; and, as external reference, opiate-user arrestees in France and hepatitis C diagnosed ever-injectors in Scotland in 1993-2001, both followed by database linkage to December 2001. EMCDDA cohorts recorded approximately equal numbers of drugs-related deaths (864) and deaths from other non-HIV causes (865) during 106,152 person-years of follow-up. External cohorts contributed 376 drugs-related deaths (Scotland 195, France 181) and 418 deaths from non-HIV causes (Scotland 221, France 197) during 86,417 person-years of follow-up (Scotland 22,670, France 63,747). EMCDDA cohorts reported 707 drugs-related deaths in 81,367 man-years {8.7 per 1000 person-years, 95% CI: 8.1 to 9.4} but only 157 in 24,785 person-years for females {6.3 per 1000 person-years, 95% CI: 5.4 to 7.4}. Except in external cohorts, relative risks by current age-group were not particularly strong, and more modest in Poisson regression than in cross-sectional analyses: relative risk was 1.2 (95% CI: 1.0-1.4) for 35-44 year olds compared to 15-24 year 3 olds, but 1.4 for males (95%CI: 1.2-1.6), and dramatically lower at 0.44 after the first year of follow-up (95% CI: 0.37-0.52)

Closing Evidence Gaps on the Prevalence and Harms of New Psychoactive Substances in Scotland

This paper considers the state of knowledge on New Psychoactive Substances (NPS) in Scotland, with a focus on prevalence and harms and puts forward proposals which may assist in closing existing evidence gaps

Novel psychoactive substances (NPS) – knowledge and experiences of drug users from Hungary, Poland, the UK and the USA

Submitted 19 September 2019; Accepted 29 November 2019; Proof received 29 November 2019; Published 18 February 2020. Note: No DOI allocated.Dopamine D 3 receptor partial agonists represent a new generation of atypical antipsychotics. Cariprazine, which has received centralized market authorization from the European Medicines Agency in 2017 for the treatment of adult patients with schizophrenia (including those with predominant negative symptoms of schizophrenia) differs from the other two partial agonist antipsychotics aripiprazole and brexpiprazole due to its unique features. Cariprazine is a dopamine D 3 preferring D 3/D2 partial agonist with very similar dopamine receptor sub-type selectivity as dopamine. It has proven efficacy in the treatment of positive and negative symptoms of schizophrenia, as well as for relapse prevention. Further phase-3 clinical studies proved the efficacy of cariprazine in the acute treatment of manic or mixed episodes associated with bipolar I disorder, as well as in bipolar depression. For the adjunctive treatment of major depressive disorder, phase 3 studies are in progress.Peer reviewedFinal Published versio

Public spending for illegal drug and alcohol treatment in hospitals: an EU cross-country comparison

Background: In view of the current economic crisis and the resulting austerity measures being implemented by governments across Europe, public expenditure for substance abuse treatment has increasingly become a subject of discussion. An EU cross-country comparison would allow an estimation of the total amount of public resources spent on substance abuse treatment, compare various substance abuse treatment funding options, and evaluate the division of expenditures between alcohol and illegal drugs. The purpose of this study is to estimate the public spending of EU countries for alcohol and illegal drug abuse treatment in hospitals. Methods: Our study uses a uniform methodology in order to enable valid cross-national comparisons. Our data are drawn from the Eurostat database, which provides anno 2010 data on government spending for the treatment of illegal drug and alcohol abuse in 21 EU member states. The cross-country comparison is restricted to hospitals, since data were unavailable for other types of treatment providers. The systematic registration of in- and outpatient data is essential to monitoring public expenditures on substance abuse treatment using international databases. Results: Total public spending for hospital-based treatment of illegal drug and alcohol abuse in the 21 EU member states studied is estimated to be 7.6 billion euros. Per capita expenditures for treatment of illegal drug abuse vary, ranging from 0.1 euros in Romania to 13 euros in Sweden. For alcohol abuse, that figure varied from 0.9 euros in Bulgaria to 24 euros in Austria. These results confirm other studies indicating that public expenditures for alcohol treatment exceed that for illegal drug treatment. Conclusions: Multiple factors may influence the number of hospital days for alcohol or illegal substance abuse treatment, and expenditures fluctuate accordingly. In this respect, we found a strong correlation between gross domestic product (GDP) per capita and public expenditures per hospital day. The prevalence of problematic ( illegal or legal) drug use in a country did not correlate significantly with the number of hospital days. Other factors must be included in the analysis of public expenditures for the treatment of substance abuse, such as the drug policy in a given country and the social norms regarding alcohol consumption

The role of setting for ketamine abuse: clinical and preclinical evidence

Drug abuse is often seen as a unitary phenomenon, partly as a result of the discovery over the past three decades of shared mechanisms of action for addictive substances. Yet the pattern of drug taking is often very different from drug to drug. This is particularly evident in the case of 'club drugs', such as ketamine. Although the number of ketamine abusers is relatively small in the general population, it is quite substantial in some settings. In particular, ketamine abuse is almost exclusively limited to clubs and large music parties, which suggests a major role of context in modulating the reward effects of this drug. This review focuses on recent preclinical and clinical findings, including previously unpublished data, that provide evidence that, even under controlled conditions, ketamine reward is a function of the setting of drug taking

Drugnet Europe 94.

Contents: • 2016 EU Drug Markets Report • Monitoring illicit drugs in wastewater • UNGASS 2016 • Strengthening early warning on new synthetic opioids • New EMCDDA products and services • Upcoming ESPAD report • EMCDDA scientific paper awar

Illicit substance use among university students from seven European countries: A comparison of personal and perceived peer use and attitudes towards illicit substance use

Objective: To compare European students' personal use and approval of illicit substance use with their perceptions of peer behaviours and attitudes, and investigate whether perceptions of peer norms are associated with personal use of illicit substances and attitudes. Method: This study used baseline data fromthe Social Norms Intervention for the prevention of Polydrug usE (SNIPE) project involving 4482 students from seven European countries in 2012. Students completed an online surveywhich included questions on personal and perceived peer illicit substance use and personal and perceived peer attitude towards illicit substances. Results: 8.3% of students reported having used illicit substances at least once in their life. 49.7% of students perceived that the majority of their peers have used illicit substances more frequently than themselves. The perception was significantly associated with higher odds for personal illicit substance use (OR: 1.97, 95% CI: 1.53–2.54). The perception that the majority of peers approve illicit substance use was significantly associated with higher odds for personal approval of illicit substance use (OR: 3.47, 95% CI: 2.73–4.41). Conclusion: Students commonly perceived that their peers used illicit subtances more often than themselves. We found an association between the perceived peer norms/attitudes and reported individual behaviour/ attitudes