Delirium Risk of Antiepileptic Drugs: A Study Based on the Adverse Drug Event Reporting Database in Japan

Abstract

Abstract Background Antiepileptic drugs may cause delirium, and the risk may vary with each drug. However, related studies have provided inconsistent results. Aim To investigate whether antiepileptic drugs cause delirium by analysing adverse drug event reports compiled in the post-marketing stages of drugs and recorded in a database established by Japanese regulatory authorities. Method A total of 573,316 reports registered between 2004 and 2020 were used to create a dataset. The search terms for delirium as the item of interest were selected from the Standardized Medical Dictionary for Regulatory Activities Queries. Reporting odds ratios and 95% confidence intervals of adverse events associated with use of antiepileptic drugs were calculated after adjusting for potential confounders. Results There were 27,194 reports of antiepileptic drug-related adverse events. Of these, 189 reports were associated with antiepileptic drugs and delirium (crude reporting odds ratio, 1.66; 95% confidence interval, 1.43–1.92). The use of lacosamide (adjusted reporting odds ratio, 2.51; 95% confidence interval, 1.28–4.94), lamotrigine (adjusted reporting odds ratio, 1.71; 95% confidence interval, 1.16–2.52), levetiracetam (adjusted reporting odds ratio, 1.82; 95% confidence interval, 1.28–2.59), and valproic acid (adjusted reporting odds ratio, 1.53; 95% confidence interval, 1.19–1.97) was related to a significantly higher reporting odds ratio for delirium, even after adjustment for possible confounding factors. However, no signals for delirium were detected with any of these drugs under benzodiazepine receptor agonist usage. Conclusion The study findings suggest that antiepileptic drugs may cause delirium.