Understanding the Opioid Epidemic through Pharmacovigilance Signals: an Analysis of Pharmacovigilance Datasets collecting Adverse Drug Reactions (ADRs) reported to EudraVigilance (EV) and the FDA Adverse Event Reporting System (FAERS) over 10 Years

Introduction In the past twenty years, the consumption of opioid medications has reached significant proportions, leading to the so-called opioid epidemic, characterized by cyclical waves of heroin use and the non-medical use of pharmaceutical opioids, increased dependence, and an alarming rate of opioid overdose deaths due to illicitly manufactured fentanyl, fentanyl analogues, and other chemicals, known as novel synthetic opioids (NOSs). The purpose of this study was to determine whether there are pharmacovigilance signals of abuse, misuse, and dependence, and their nature for the following prescription opioids: codeine, dihydrocodeine, fentanyl, oxycodone, pentazocine, and tramadol. Methods Both the pharmacovigilance datasets EudraVigilance (EV) and the FDA Adverse Events Reporting System (FAERS) were analyzed. A descriptive analysis of the selected Adverse Drug Reactions (ADRs) was performed, and pharmacovigilance signal measures (i.e., reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean) were computed for preferred terms (PTs) of abuse, misuse, dependence, and withdrawal, as well as PTs eventually related to them (e.g., aggression, euphoric mood, etc.). Results From 2003 to 2018, there was an increase in ADR reports for the selected opioids in both datasets. Overall, 16,506 and 130,293 individual ADRs for the selected opioids were submitted to EV and FAERS, respectively. Compared with other opioids, abuse concerns were mostly recorded in relation to fentanyl and oxycodone, while tramadol and oxycodone were more associated with drug dependence and withdrawal. Benzodiazepines, antidepressants, antihistamines, recreational drugs (e.g., cocaine and alcohol, etc.), and several new psychoactive substances, e.g., mitragynine and cathinones, were the most commonly reported concomitant drugs. Conclusions Pharmacovigilance databases confirmed previous data on the abuse and dependence of prescription opioids and should be considered a resource for monitoring and preventing such issues. Psychiatrists and clinicians prescribing opioids should be aware of their misuse and dependence liability and effects that may accompany their use.