Antipsychotic abuse and dependence: A 10-year review of reports to the European Pharmacovigilance System

Background: The phenomenon of antipsychotic abuse and dependence holds substantial implications for public health, intersecting with concerns regarding mental health management and societal responses to substance misuse. Understanding and addressing this issue is crucial for safeguarding the health and well-being of affected individuals.

Objectives: To assess Individual Case Safety Reports (ICSRs) associated with antipsychotic abuse and dependence reported to the European Pharmacovigilance System over the last 10 years.

Methods: We conducted a retrospective analysis of ICSRs containing at least one medicinal product classified under the Anatomical Therapeutic Chemical (ATC) group NO5A (antipsychotics), reported as suspect or interacting to the EudraVigilance database, from January 1, 2014, to December 31, 2023. ICSRs with at least one MedDRA Preferred Term (PT) under the Standardised MedDRA Query (SMQ) narrow terms “Drug abuse and dependence” were included. The number of ICSRs per ATC 4th and 5th level was measured, along with patient demographic data, category of adverse drug reaction (MedDRA PT), seriousness, and the type of pharmacological substance reported concomitantly. Descriptive methods were used for statistical analysis.

Results: A total of 8613 ICSRs were identified, with 52.4% (n=4512) of these concerning women and 71.0% (n=6113) involving individuals aged between 18 and 64 years old. Among the ICSRs, the majority (57.1%; n=4914), contained at least one medicinal product classified under the ATC group N05AH (diazepines, oxazepines, thiazepines, and oxepines), with quetiapine being the most reported medicinal product, representing 36.7% (n=3164) of the total reports. Regarding seriousness, 95.3% (n=8205) of the ICSRs were classified as serious, with 39.7% (n=3420) leading to hospitalization and 13.9% (n=1201) resulting in the death of the individual. One-fifth of the reports (n=1735) were related to cases of suicide attempt. Somnolence was the most frequently reported adverse drug reaction, occurring in 11.4% (n=984) of cases. The most frequently reported therapeutic classes concomitantly were antidepressants, anxiolytics, and antiepileptics, noting that approximately 8% (n=662) of the ICSRs referred to the concurrent use of ethanol, cocaine, or cannabis.

Conclusions: Our findings reinforce the urgent need to address antipsychotic abuse and dependence, given their profound societal implications. Furthermore, it is important to note that the extent of this issue may exceed our current understanding, due to potential underreporting and the influence of existing pharmacovigilance regulations.