Is There a Potential of Misuse for Quetiapine?

This document is the Accepted Manuscript version. Under embargo until 28 February 2019. Reprinted from Journal of Clinical Psychopharmacology, Vol. 31(1): 72-79, February 2018, with permission of Kluwer Law International.Purpose/Background A recent years' increase in both prescribing and availability of second-generation antipsychotics (SGAs) has been observed. According to the literature, typically made up by case studies/series, quetiapine seems to be the most commonly misused SGA, with both intranasal and intravenous intake modalities having been described. Another SGA that has been anecdotally reported to be misused is olanzapine. For these molecules, both a previous history of drug misuse and being an inmate have been described as factors associated with misuse. Hence, while providing here an updated literature review of the topic, we aimed at assessing all cases of quetiapine misuse/abuse/dependence/withdrawal as reported to the European Medicines Agency's EudraVigilance (EV) database; this was carried out in comparison with the reference drug olanzapine. Methods All spontaneous, European Medicines Agency database reports relating to both quetiapine (2005-2016) and olanzapine (2004-2016) misuse/abuse/dependence/withdrawal issues were retrieved, and a descriptive analysis was performed. Results From the EV database, 18,112 (8.64% of 209,571) and 4178 (7.58% of 55,100) adverse drug reaction reports of misuse/abuse/dependence/withdrawal were associated with quetiapine and olanzapine, respectively. The resulting proportional reporting ratio values suggested that the misuse/abuse-, dependence-, and withdrawal-related adverse drug reactions were more frequently reported for quetiapine (1.07, 1.01, and 5.25, respectively) in comparison with olanzapine. Conclusions Despite data collection limitations, present EV data may suggest that, at least in comparison with olanzapine, quetiapine misuse may be a cause for concern.Peer reviewedFinal Accepted Versio

A Decade of Gabapentinoid Misuse: : An Analysis of the European Medicines Agency’s ‘Suspected Adverse Drug Reactions’ Database

This document is the Accepted Manuscript version of the following article: Stefania Chiappini, and Fabrizio Schifano, ‘A Decade of Gabapentinoid Misuse: An Analysis of the European Medicines Agency’s ‘Suspected Adverse Drug Reactions’ Database’, CNS Drugs, Vol. 30 (7): 647-654, July 2016. The final publication is available at Springer via https://doi.org/10.1007/s40263-016-0359-y. © 2016 Springer International Publishing. he paper was firstly submitted on December 16, 2015; last revised on May 24, 2016; accepted on May 31, 2016; and published online on June 16, 2016.Introduction: The gabapentinoids pregabalin and gabapentin are being increasingly prescribed for a range of clinical conditions. Recently, although gabapentinoids at therapeutic dosages may present with low addictive liability levels, cases of misuse and rising numbers of related fatalities have been reported. Objectives: The aim of the study was to identify and assess cases of gabapentinoid misuse or dependence as reported to the European Medicines Agency’s EudraVigilance database, to identify the magnitude of this problem and the characteristics of these reactions. Methods: All spontaneous reports of both gabapentin- (2004–2015) and pregabalin- (2006–2015) related misuse/abuse/dependence were retrieved. A descriptive analysis by source, sex, age, and type of report was performed. Results: From the EudraVigilance database 7639 (6.6 % of a total of 115,616) and 4301 (4.8 % of 90,166) adverse drug reaction reports of misuse/abuse/dependence were, respectively, associated with pregabalin and gabapentin, with an overall reporting frequency increasing over time. For both molecules, subjects typically involved were female adults. A total of 27 and 86 fatalities, respectively, associated with pregabalin and gabapentin, and mostly in combination with opioids, were identified. Analysis of proportional reporting ratios for drug abuse/dependence/intentional product misuse values seem to indicate that these adverse drug reactions were more frequently reported for pregabalin (1.25, 1.39, and 1.58, respectively) compared with gabapentin. Conclusions: Despite data collection/methodological approach limitations, the present data seem to suggest that gabapentinoid misuse may be a cause for concern, especially in patients with a history of substance misuse. Hence, healthcare professionals should be vigilant when prescribing these molecules.Peer reviewedFinal Accepted Versio

An update on psychoactive substances: Pharmacology and Toxicology issues

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Peer reviewe

Editorial: Prescribing Psychotropics: Misuse, Abuse, Dependence, Withdrawal and Addiction

© 2021 Chiappini, Schifano and Martinotti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/Peer reviewedFinal Published versio

Use of Medicinal Cannabis and Synthetic Cannabinoids in Posttraumatic Stress Disorder (PTSD): a systematic review

Background and Objectives: Post-traumatic stress disorder (PTSD) is a common psychiatric disorder resulting from a traumatic event, is manifested through hyperarousal, anxiety, depressive symptoms, and sleep disturbances. Despite several therapeutic approaches being available, both pharmacological and psychological, recently a growing interest has developed in using cannabis and synthetic cannabinoids stems from their consideration as more efficient and better tolerated alternatives for the treatment of this condition. The present paper aims to evaluate the clinical and therapeutic potentials of medical cannabis and synthetic cannabinoids in treating PTSD patients. Methods: A systematic electronic search was performed, including all papers published up to May 2019, using the following keywords (((cannabis[Title/Abstract]) OR (synthetic cannabinoids [Title/Abstract])) AND ((PTSD[Title/Abstract]) OR (Posttraumatic stress disorder[Title/Abstract]))) for the topics ‘Cannabis’, ‘Synthetic Cannabinoids’, ‘PTSD’, and MESH terms, on the PubMed, Cochrane Library, and Web of Science online databases. For data gathering purposes, PRISMA guidelines were followed. Results were organized into two groups, considering cannabis and synthetic cannabinoids as different therapeutic approaches for PTSD. Results: Present data show that cannabis and synthetic cannabinoids, both acting on the endocannabinoids system, may have a potential therapeutic use for improving PTSD symptoms, e.g., reducing anxiety, modulating memory-related processes, and improving sleep. Conclusions: Even though the current literature suggests that cannabis and synthetic cannabinoids may have a role in the treatment of PTSD, there is currently limited evidence regarding their safety and efficacy. Therefore, additional research is needed in order to better understand the effectiveness and therapeutic usage of these drug classes and monitor their safety.Peer reviewe

Beyond the ‘purple drank’: Study of promethazine abuse according to the European Medicines Agency adverse drug reaction reports

Submitted 30 April; revisions submitted 17 July 2020; accepted 8 August 2020; first published 10 January 2021.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 aimed at studying how this phenomenon has been reported to the European Monitoring Agency (EMA) Adverse Drug Reactions (ADRs) database. Methods: After a formal request to the EMA, the promethazine-specific dataset has been studied performing a descriptive analysis of the misuse/abuse/dependence related-ADR 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 1,543 ADRs’ cases, 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 ADRs. 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 EMA 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.Peer reviewe

Climate change, biodiversity loss and mental health: a global perspective

Climate change can have various psychopathological manifestations which have been more actively addressed by scientific research only in recent years. Indeed, extreme weather events and environmental changes have been shown to be associated with a range of mental health problems. Following the destruction of ecosystems, biodiversity loss can cause mental distress and emotional responses, including so-called 'psychoterratic' syndromes arising from negatively felt and perceived environmental change. Studies investigating relationships between biodiversity and mental health reveal a complex landscape of scientific evidence, calling for a better understanding of this challenging issue

COVID-19: The hidden impact on mental health and drug addiction

© 2020 Chiappini, Guirguis, John, Corkery and Schifano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY - https://creativecommons.org/licenses/by/4.0/). 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.There is concern the Coronavirus Disease (COVID)-19 pandemic is having a negative impact on the mental health of the general population through a range of suggested mechanisms: fear, uncertainty, and anxiety; social distancing/isolation; loneliness; and economic repercussions (1–3). Previous disasters such as the Severe Acute Respiratory Syndrome (SARS) in 2003 (4–6) contributed to increased anxiety, mood, and thought disorders, adjustment disorders, and post-traumatic stress disorders (PTSD) (1, 7–15), resulting, in extreme cases, in suicidal behaviours (e.g., suicidal ideation, suicide attempts, and actual suicide) (10, 16), especially in cases of concomitant Substance Use Disorder (SUD) (17, 18). According to a recent study from the Well Being Trust (18) the high levels of stress, isolation and unemployment due to the COVID-19 pandemic could cause up to 75,000 “deaths of despair” related to deaths to drug, alcohol, and suicide (18). High risk of mental illness was previously identified in individuals with existing or history of mental illnesses (1, 9, 12, 14, 19), but also vulnerable categories might be considered the elderly (>80 years old), children/adolescents, individuals from deprived areas, peri-natal women and BAME (Black, Asian and minority ethnicities) (1, 12, 14, 19). Finally, healthcare workers have been experiencing emotional overload due to several reasons, including both organizational issues relating to the shortage of suitable personal protective equipment, reduction in human resources and relentless work shifts (20–23), but also the burden developed by the fear of becoming infected and infecting relatives, high mortality rates, grieving the loss of patients and colleagues, separation from families (22–24). Specifically, according to Huang et al. (25), among the first-line medical staff of a Tertiary Infectious Disease Hospital for COVID-19 in China, the incidence of anxiety and post traumatic symptoms in female medical staff was higher than that in male, and in nurses more represented than that in doctors (25).Peer reviewe

A Focus on Abuse/Misuse and Withdrawal Issues with Selective Serotonin Reuptake Inhibitors (SSRIs): Analysis of Both the European EMA and the US FAERS Pharmacovigilance Databases

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)Despite increasing reports, antidepressant (AD) misuse and dependence remain underestimated issues, possibly due to limited epidemiological and pharmacovigilance evidence. Thus, here we aimed to determine available pharmacovigilance misuse/abuse/dependence/withdrawal signals relating to the Selective Serotonin Reuptake Inhibitors (SSRI) citalopram, escitalopram, paroxetine, fluoxetine, and sertraline. Both EudraVigilance (EV) and Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) datasets were analysed to identify AD misuse/abuse/dependence/withdrawal issues. A descriptive analysis was performed; moreover, pharmacovigilance measures, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayesian geometric mean (EBGM) were calculated. Both datasets showed increasing trends of yearly reporting and similar signals regarding abuse and dependence. From the EV, a total of 5335 individual ADR reports were analysed, of which 30% corresponded to paroxetine (n = 1,592), 27% citalopram (n = 1,419), 22% sertraline (n = 1,149), 14% fluoxetine (n = 771), and 8% escitalopram (n = 404). From FAERS, a total of 144,395 individual ADR reports were analysed, of which 27% were related to paroxetine, 27% sertraline, 18% citalopram, 16% fluoxetine, and 13% escitalopram. Comparing SSRIs, the EV misuse/abuse-related ADRs were mostly recorded for citalopram, fluoxetine, and sertraline; conversely, dependence was mostly associated with paroxetine, and withdrawal to escitalopram. Similarly, in the FAERS dataset, dependence/withdrawal-related signals were more frequently reported for paroxetine. Although SSRIs are considered non-addictive pharmacological agents, a range of proper withdrawal symptoms can occur well after discontinuation, especially with paroxetine. Prescribers should be aware of the potential for dependence and withdrawal associated with SSRIs.Peer reviewedFinal Published versio

3-Methoxy-Phencyclidine Induced Psychotic Disorder: A Literature Review and an 18 F-FDG PET/CT Case Report

© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/New Psychoactive Substances (NPS) are modifying the drug scenario worldwide and have become a public health concern because of their toxicological profiles and their harmful physical/psychological effects. 3-Methoxy-Phencyclidine (3-MeO-PCP), a non-competitive antagonist of glutamate N-methyl-D-aspartate (NMDA) receptors, belongs to the phencyclidine-like subfamily of arylcyclohexylamines and has gained attention for its toxic, sometimes fatal, effects. Despite several cases of intoxication and death reported in the literature, little is known about substance-induced psychotic disorders (SIP) and potential cognitive impairment following 3-MeO-PCP intake. This literature review aimed to summarize available evidence about 3-MeO-PCP mechanisms of action and physical and psychotropic effects and to spread preliminary findings about persistent psychotic symptoms and impaired cognitive functioning. Additionally, the case of an SIP is reported in a 29-year-old man with small oral intakes of 3-MeO-PCP over two weeks until a high dose ingestion. Psychometric and neuropsychological assessment and brain [18F]-fluorodeoxyglucose positron emission tomography integrated with computed tomography were used to support clinical description. Identifying and addressing the characteristic clinical features and neural substrates of NPS-induced psychoses might help clinicians with a more precise differentiation from other psychotic disorders. Although further studies are required, phenotyping the cognitive profile of NPS users might provide targets for tailored therapeutic approaches.Peer reviewe