Safety profile of chloroquine and hydroxychloroquine: a disproportionality analysis of the FDA Adverse Event Reporting System database.

OBJECTIVE: The present study aims to identify potential safety signals of chloroquine (CQ) and hydroxychloroquine (HCQ), over the period preceding their repurpose as COVID-19 treatment options, through the analysis of safety data retrieved from the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database. MATERIALS AND METHODS: We performed a disproportionality analysis of FAERS data between the first quarter of 2004 and December 2019 using the OpenVigil2.1-MedDRA software. Disproportionality was quantified using the reporting odds ratio (ROR) and its 95% confidence interval (CIs). The reported mortality of CQ and HCQ was also investigated. RESULTS: The dataset contained 6,635,356 reports. Comparison of the RORs revealed significant differences between CQ and HCQ for the following adverse events: cardiomyopathy, cardiac arrhythmias, retinal disorders, corneal disorders, hearing disorders, headache, hepatic disorders, severe cutaneous reactions, musculoskeletal disorders, and cytopenia. Only CQ was associated with psychotic disorders, suicide, self-injury, convulsions, peripheral neuropathy, and decreased appetite. In multivariable logistic regression, death was more frequently associated with CQ use, advanced age, male sex, co-reported suicide and self-injury, cardiomyopathy, cardiac arrhythmias, and decreased appetite. CONCLUSIONS: Our results confirm previously published evidence and suggest that HCQ has a safer clinical profile compared to CQ, and thus could serve as the drug of choice for future therapeutic purposes.

A white paper on a neurodevelopmental framework for drug discovery in autism and other neurodevelopmental disorders.

In the last decade there has been a revolution in terms of genetic findings in neurodevelopmental disorders (NDDs), with many discoveries critical for understanding their aetiology and pathophysiology. Clinical trials in single-gene disorders such as fragile X syndrome highlight the challenges of investigating new drug targets in NDDs. Incorporating a developmental perspective into the process of drug development for NDDs could help to overcome some of the current difficulties in identifying and testing new treatments. This paper provides a summary of the proceedings of the 'New Frontiers Meeting' on neurodevelopmental disorders organised by the European College of Neuropsychopharmacology in conjunction with the Innovative Medicines Initiative-sponsored AIMS-2-TRIALS consortium. It brought together experts in developmental genetics, autism, NDDs, and clinical trials from academia and industry, regulators, patient and family associations, and other stakeholders. The meeting sought to provide a platform for focused communication on scientific insights, challenges, and methodologies that might be applicable to the development of CNS treatments from a neurodevelopmental perspective. Multidisciplinary translational consortia to develop basic and clinical research in parallel could be pivotal to advance knowledge in the field. Although implementation of clinical trials for NDDs in paediatric populations is widely acknowledged as essential, safety concerns should guide each aspect of their design. Industry and academia should join forces to improve knowledge of the biology of brain development, identify the optimal timing of interventions, and translate these findings into new drugs, allowing for the needs of users and families, with support from regulatory agencies.

Prevalence of illicit drug use among medical students in Northern Greece and association with smoking and alcohol use.

AIM: The aim of this study was to estimate the prevalence of illicit drug use among medical students in Northern Greece, to identify the motivations for cannabis use and also to investigate the possible associations with smoking and alcohol misuse. METHODS: A sample of undergraduate students completed an anonymous, self-administered, web-based survey assessing lifetime and past-year illicit substance use. To further evaluate the motivation to use, the responders were classified into three subtypes (self-medication, recreational, and mixed). The CAGE questionnaire and a question assessing binge drinking were also used. Illicit substance use was correlated with age, gender, study year, CAGE and binge drinking. RESULTS: Five hundred and ninety-one undergraduate medical students completed the survey. The lifetime prevalence of illicit drug use was 24.7 %, while the most used drug was cannabis (22.2 %). The past-month prevalence of cannabis use was 8.1 %. Experimentation was the predominant reported motivation for its use, and the recreational subtype was the most prevalent. Binge drinking behavior was reported by 22.7 % of the sample, and the CAGE screening test was positive for 6.4 % of the students. Most students (80.4 %) characterized themselves as non-smokers. In the multivariate analysis, lifetime use of illicit drugs was significantly correlated with smoking and binge drinking. No associations were found with gender, age, study year or CAGE. CONCLUSION: Smoking and binge drinking were found to be risk factors for illicit drug use, whereas no association was found with gender, age, study year and CAGE. HIPPOKRATIA 2017, 21(1): 13-18.