Risk of delirium with antiepileptic drug use: a study based on the Japanese Adverse Drug Event Report database

Background Antiepileptic drugs may cause delirium, and the risk may vary with each drug. However, related studies have provided inconsistent results. Aim The aim of this study was to investigate whether the use of antiepileptic drugs is a risk factor for delirium development. Method Using the Japanese Adverse Drug Event Report database, we analysed 573,316 reports pertaining to the period from 2004 to 2020. Reporting odds ratios and 95% confidence intervals of delirium associated with use of antiepileptic drugs were calculated after adjusting for potential confounders. Furthermore, for each antiepileptic drug, we performed an analysis stratified based on older age and benzodiazepine receptor agonist usage. Results There were 27,439 reports of antiepileptic drug-related adverse events. Of these, 191 reports were associated with antiepileptic drugs and delirium (crude reporting odds ratio [cROR], 1.66; 95% confidence interval [CI], 1.43–1.93). The use of lacosamide (adjusted reporting odds ratio [aROR], 2.44; 95% CI, 1.24–4.80), lamotrigine (aROR, 1.54; 95% CI, 1.05–2.26), levetiracetam (aROR, 1.91; 95% CI, 1.35–2.71), and valproic acid (aROR, 1.49; 95% CI, 1.16–1.91) was related to a significantly higher reporting odds ratio for delirium, even after adjustment for possible confounding factors. However, when used in combination with benzodiazepine receptor agonists, none of the antiepileptic drugs were found to be associated with delirium. Conclusion Our study’s findings suggest that antiepileptic drug usage may be associated with delirium development.