Abstract
Background and Aims
The current opioid epidemic in the USA began 20 years ago and has become the leading cause of accidental deaths in the country. This crisis prompted us to explore trends in opioid abuse and dependence worldwide. We sought to identify other countries at high-risk of opioid use disorders, using the World Health Organization’s (WHO) pharmacovigilance database.
Methods
We performed a disproportionality analysis using VigiBase, the WHO global Individual Case Safety Report (ICSR) database. Five opioids used worldwide were included: oxycodone, fentanyl, morphine, tramadol and codeine. We extracted all ICSRs associated with the drugs of interest, considered as suspect medication and recorded up until 5 June 2021, using the narrow Standardised MedDRA Query (SMQ) for drug abuse and dependence. Countries with at least one ICSR for each of the 5 opioids were retained. The relationship between the use of a drug (i.e. an opioid) and the occurrence of an adverse drug reaction (i.e. drug abuse and dependence) for each country was assessed by calculating the Information Component (IC) and its 99.9% confidence interval [IC0005;IC9995], using a quasi-Bayesian Confidence Propagation Neural Network (BCPNN). A hierarchical cluster analysis (Ward’s method) of the IC0005 value for each of the 5 opioids was performed in order to identify subgroups of countries with similar reported risks of opioid abuse and dependence.
Results
Among 21 countries, the optimal number of clusters was calculated to be four, each with a Jaccard index greater than 0.5 (0.95, 0.78, 0.65, and 0.75 respectively). Six countries with the highest signals of drug abuse and dependence were identified in cluster 1, with significant confidence intervals for the 5 opioids of interest (IC0005>0), ranging from 0.9 to 5.8 for the lower endpoint.
Conclusions
There appear to be four distinct clusters of countries with similar opioid abuse and dependence profiles. The group with the highest reported risk for the opioids oxycodone, fentanyl, morphine, tramadol and codeine includes Australia, Canada, France, Germans, the UK, and the USA.