Abuse, dependence and withdrawal associated with fentanyl and the role of its (designated) route of administration: an analysis of spontaneous reports from Europe

PURPOSE: Fentanyl, a highly potent synthetic opioid used in cancer and non-cancer pain, is approved for various routes of administration. In Europe, fentanyl consumption increased substantially in the last decades but information on abuse, dependence and withdrawal associated with fentanyl is scarce, especially with respect to its different formulations. METHODS: We analysed case characteristics of spontaneous reports of suspected fentanyl-associated abuse, dependence or withdrawal from European countries recorded in the EudraVigilance database up to 2018 with respect to the (designated) routes of administration and potential indications. RESULTS: A total of 985 reports were included (mainly from France and Germany) with 43% of cases referring to transdermal fentanyl. Median age was 45 years (48.8% female) and 21.6% had musculoskeletal disorders. Only 12.6% of those using transdermal fentanyl had a cancer diagnosis compared to 40.2% and 26.8% of those using intranasal and oral transmucosal fentanyl, respectively. Depression was common (10.7%) and highest in cases with musculoskeletal disorders (24.9%) as was the use of benzodiazepines. Overall, 39.5% of reports resulted in a prolonged hospital stay and for 23.2% a fatal outcome was recorded. The respective proportions were especially high in cases with musculoskeletal disorders (56.3% with prolonged hospitalisation) and in those using transdermal fentanyl (35.2% fatalities). CONCLUSIONS: In suspected cases of abuse, dependence or withdrawal, fentanyl was mainly used for non-cancer pain indications and most often as transdermal formulations. Depression and prolonged hospitalisations were common, especially in patients with musculoskeletal disorders, indicating a vulnerable patient group and complex treatment situations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00228-022-03431-x.