Real-World Data Mining for Signal Detection of Antipsychotics-Associated Adverse Events Using the Korea Adverse Event Reporting System (KAERS) Database

Abstract

Background and Objectives: Recent studies suggest that the binary categorization of first-generation antipsychotics (FGAs) as being primarily responsible for extrapyramidal symptoms (EPSs) and second-generation antipsychotics (SGAs) for cardiometabolic abnormalities is an oversimplification. SGAs also demonstrate antagonistic affinity for D2 receptors, indicating their potential to induce EPSs. This study utilized the Korea Adverse Event Reporting System (KAERS) database to explore adverse drug event (ADE) signals related to both FGAs and SGAs. Materials and Methods: Relevant ADE reports from January 2013 to December 2022 were extracted from the KAERS database and analyzed using disproportionality analysis, employing the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) with its 95% lower confidence interval (LCI) indices. Results: Of the initial dataset of 2,890,702 ADE reports, those with insufficient data and duplicates were removed, resulting in a final dataset of 5249 reports for analysis. Aripiprazole, an SGA, showed signals for movement disorders, including EPSs (PRR 4.7, ROR 4.8, IC 2.2), tremors (PRR 5.3, ROR 5.4, IC 2.4), and akathisia (PRR 18.6, ROR 19.3, IC 3.5). Notably, for quetiapine, cardiovascular signals were detected, including increased blood pressure (PRR 2.1, ROR 2.3, IC 0.5), and tachyarrhythmia (PRR 13.9, ROR 14.1, IC 1.8), along with peripheral edema (PRR 2.5, ROR 2.5, IC 0.2). Metabolic abnormalities, such as weight gain and increased appetite, were identified for four SGAs: aripiprazole, olanzapine, quetiapine, and risperidone. Safety signals related to movement disorders were not detectable for FGAs, likely due to the limited number of ADE reports available for analysis. Conclusions: Our study findings support that the distribution of ADEs between FGAs and SGAs is not strictly binary. Aripiprazole, despite being an SGA, showed signals for extrapyramidal movement disorders. Four SGAs (aripiprazole, olanzapine, quetiapine, and risperidone) were linked to metabolic side effects, while quetiapine was associated with cardiovascular safety signals.

Keywords

• antipsychotics
• drug-induced movement disorders
• adverse drug events
• pharmacovigilance
• disproportionality analysis
• signal detection analysis