Among over-the-counter (OTC) drugs, loperamide has recently emerged for its potential of misuse and cardiotoxicity issues. Hence, we aimed here at assessing the loperamide-related cases being ...reported to the EMA's EudraVigilance (EV) database.
All spontaneous EV reports relating to loperamide misuse/abuse/dependence/withdrawal and cardiotoxicity issues were here retrieved, performing a descriptive analysis.
During the years 2005-2017, EV collected a number of 1,983 (out of a total of 7,895; 25.11%) loperamide-related misuse/abuse/dependence/withdrawal adverse drug reaction (ADR) reports, with a progressively increasing trend since 2014. Most cases were classified as drug use disorder (37.4%) or intentional overdose (25.4%). Loperamide was used on its own in 41.9% of cases; remaining, polydrug, cases included antidepressants; benzodiazepines; and other OTCs. Some 1,085 (1,085/7,895 = 13.7%) cardiovascular ADRs were reported, being conduction abnormalities and EKG alterations the most frequently identified.
EV data may support the levels of concern relating to loperamide potential of abuse and associated cardiotoxicity issues.
Recently, a range of prescription and over-the-counter (OTC) drugs have emerged as being used recreationally, either on their own or in combination with other substances, both licit and illicit, ...including new psychoactive substances (NPS). Among them, the misuse of prescription drugs involves not only traditionally recorded substances, such as benzodiazepines and opioid pain relievers, but also gabapentinoids (e.g., pregabalin and gabapentin); some antidepressants, e.g., bupropion and venlafaxine; some second-generation antipsychotics, e.g., quetiapine and olanzapine. Moreover, the use of some OTC for recreational purposes appears on the increase, especially in vulnerable categories such as young people/youths, including the use of high dosages of the antidiarrheal loperamide; first-generation antihistamines, e.g., promethazine, cyclizine, and diphenhydramine; cough and cold preparations containing dextromethorphan and/or codeine. In this context, the role of the Internet has rapidly increased, playing a significant role both in the diffusion of emerging trends of drug misuse among users and experimenters, and the marketing, sale, and distribution of drugs through online pharmacies. This phenomenon within the context of a rapidly modifying drug scenario is a globally recognized health problem, determining severe adverse consequences, including fatalities, and represents a challenge for clinicians in general, psychiatrists, public health, and drug-control policies.
This Special Issue, titled “Psychoactive Substances: Pharmacology and Toxicology”, aims to provide an up-to-date overview of the pharmacology, clinical information, and toxicology of psychotropics, ...as well as the effects associated with their intake ...
Background:
Promethazine is a medicinal product, available on its own or in combination with other ingredients including dextromethorphan, paracetamol and/or expectorants. Anecdotal reports have ...however indicated that promethazine may have a misuse potential, especially in adolescents.
Objective:
We here aimed at studying how this phenomenon has been reported to the European Monitoring Agency Adverse Drug Reactions database.
Methods:
After a formal request to the European Monitoring Agency, the promethazine-specific dataset has been studied, performing a descriptive analysis of misuse/abuse/dependence-related adverse drug reaction reports. The study was approved by the University of Hertfordshire (LMS/PGR/UH/03234).
Results:
The analysis of promethazine data showed increasing levels of misuse/abuse/ dependence issues over time (2003–2019). Out of a total number of 1543 cases of adverse drug reactions, the abuse/misuse/dependence-related cases reported were 557, with ‘drug abuse’ (300/557: 53.8%) and ‘intentional product misuse’ (117/557: 21.0%). being the most represented adverse drug reactions. A high number of fatalities were described (310/557: 55.6%), mostly recorded as ‘drug toxicity/drug abuse’ cases, with opiates/opioids having been the most commonly reported concomitant drugs used.
Conclusion:
Anecdotal promethazine misuse/abuse reports have been confirmed by European Monitoring Agency data. Promethazine misuse/abuse appears to be an alarming issue, being associated with drug-related fatalities. Thus, healthcare professionals should be warned about a possible misuse of promethazine and be vigilant, as in some countries medicinal products containing promethazine can be purchased over the counter. Since promethazine is often available in association with opioids, its abuse may be considered a public health issue, with huge implications for clinical practice.
Traditionally, studies on the non-medical use of pharmaceutical products have focused on controlled substances; e.g., opiates/opioids; and benzodiazepines. Although both bupropion and venlafaxine ...have been reported as being misused, only anecdotal reports have been made available so far. Hence, the European Monitoring Agency (EMA) Adverse Drug Reactions (ADRs), misuse/abuse/dependence and withdrawal, venlafaxine- and bupropion-related, database was here analyzed.
All EMA spontaneous reports relating to venlafaxine (2005-2016) and bupropion (2003-2016) notifications were here analyzed, to provide a descriptive analysis by source, gender, age, and type of report. The UK-based, 2000-2016, Yellow Card Scheme pharmacovigilance database, bupropion and venlafaxine withdrawal reports were compared as well with those pertaining to fluoxetine and paroxetine.
Out of 20,720 (bupropion) and 47,516 (venlafaxine) total number of ADRs, some 2,232 (10.8%), and 4,071 (8.5%) misuse/abuse/dependence ADRs were respectively associated with bupropion and venlafaxine. Conversely, bupropion withdrawal-related ADRs were here reported in 299/20,720 (1.44%) cases and in 914/47,516 (1.92%) cases for venlafaxine. Overall, all bupropion and venlafaxine misuse-/abuse-/dependence- and withdrawal-ADRs were related to a respective number of 264 and 447 patients. According to the Proportional Reporting Ratio (PRR) computation, in comparison with venlafaxine bupropion resulted to be more frequently misused/abused (PRR: 1.50), but less frequently associated with both dependence (PRR: 0.92) and withdrawal (PRR: 0.77) issues. Yellow Card Scheme data suggested that paroxetine and venlafaxine, in comparison with fluoxetine and bupropion, were associated with higher number of withdrawal-related reports.
The dopaminergic, stimulant-like, bupropion activities may be associated with its possible recreational value. Present data may confirm that the occurrence of a withdrawal syndrome may be a significant issue for venlafaxine-treated patients.
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.
Descriptive analysis of both ADRs and related cases.
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
= 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%).
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.
Background:
The benzodiazepine drug alprazolam, a fast-acting tranquiliser, cannot be prescribed on the National Health Service in the United Kingdom. Illicit alprazolam supply and consumption have ...increased. Concern about increasing numbers of alprazolam-related fatalities started circulating in 2018. However, statistics on this issue are very limited. This study examined patterns in such mortality in Scotland.
Methods:
Statistics on deaths where alprazolam was mentioned in the ‘cause of death’ were obtained from official mortality registers. Anonymised Scottish case-level data were obtained. Data were examined in respect of the characteristics of decedents and deaths using descriptive statistics.
Results:
Scotland registered 370 deaths in 2004–2020; 366 of these occurred in 2015–2020: most involved males (77.1%); mean age 39.0 (SD 12.6) years. The principal underlying cause of death was accidental poisoning: opiates/opioids (77.9%); sedatives/hypnotics (15.0%). Two deaths involved alprazolam alone. Main drug groups implicated: opiates/opioids (94.8%), ‘other benzodiazepines’ (67.2%), gabapentinoids (42.9%), stimulants (30.1%), antidepressants (15.0%). Two-thirds (64.2%) involved combinations of central nervous system (CNS) depressants.
Discussion:
Alprazolam-related deaths are likely due to an increasing illicit supply. The fall in deaths in 2019–2020 is partially due to increased use of designer benzodiazepines. Treatment for alprazolam dependence is growing. Clinicians need to be aware of continuing recreational alprazolam use. When such consumption occurs with CNS depressants, overdose and death risks increase.
Conclusions:
More awareness of alprazolam contributing to deaths, especially in conjunction with other CNS depressants, is needed by consumers and clinicians. Improved monitoring of illicit supplies could identify emerging issues of medicines’ abuse.
Background: NPS belonging to the benzodiazepine (BZD) class, e.g., ‘legal/designer BZDs’/‘research chemicals’, have recently emerged in the drug (mainly online/virtual) market.
Objective: ...While certain NPS belonging to the BZD class possess pharmacological profiles similar to controlled pharmaceutical BZDs, clinical and pharmacological profiles of current emerging BZDs are still not well-described. Therefore, there is a need to increase clinicians’/public health knowledge/awareness, to incentive harm reduction strategies.
Method: A comprehensive overview was carried out by using the EMCDDA/EDND database regularly monitored by our research team, by specifically looking at the ‘new BZDs’ so far notified. Furthermore, given the limitation of peer-reviewed data published so far, a nonparticipant multilingual qualitative netnographic study was conducted to obtain further clinical/pharmacological/ toxicological data, including psychonauts’ online trip reports.
Results: First designer BZDs appeared as NPS around 2007. So far, 29 designer BZDs have been notified to the EMCDDA, being some of them extremely powerful, also at lower dosages. They are sold as tablets/powder/pellets/capsules/blotters/liquids, at very affordable prices, and variably administered. Some are also sold on the illicit drugmarket as counterfeit forms of traditional BZDs or as either adulterants or diluents in heroin or other synthetic opioids/cannabinoids. Nowadays, there is no guarantee of the quality of designer BZDs composition/purification and, hence, most NPS consumers may be inadvertently exposed to unsafe and harmful compounds.
Conclusion: Given the limited information on their pharmacology/toxicity, variations in dosage, onset of effects, combination of substances, potency, and general patient or individual variability, the concomitant use of these substances with other drugs entails several and unpredictable risks.
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