JADERを用いた睡眠薬と強抗コリン薬の併用における認知症・せん妄報告の相互作用評価

抄録

This study aimed to assess whether the concomitant use of hypnotics and strong anticholinergic drugs is associated with an interaction in reports of dementia and delirium using a reporting database. We analyzed the Japanese Adverse Drug Event Report (JADER) database from 2015 to 2024. Outcomes were defined using MedDRA/J Standardized MedDRA Queries (SMQs) for dementia and delirium (narrow and broad), with broad SMQs used as the primary outcomes. Hypnotics were categorized into three groups: GABAergic ultra–short-acting, short- to intermediate-acting GABAergic, and non-GABAergic (orexin receptor antagonists and melatonin receptor agonists). Strong anticholinergic drugs were selected primarily from drugs with a Japanese Anticholinergic Risk Scale score of 3 and classified into five groups: first-generation H1 antihistamines, tricyclic antidepressants, overactive bladder antimuscarinics, chlorpromazine, and antiparkinsonian anticholinergics. Older adults were defined as individuals aged ≥70 years. Associations were evaluated using odds ratios. Interactions were assessed using generalized linear models (binomial distribution) with an identity link (additive model; risk difference) and a log link (multiplicative model). In older adults, reports of dementia and delirium (broad SMQs) were relatively frequent in the hypnotic groups and tended to be higher than the overall background for the strong anticholinergic groups. However, the concomitant exposure was sparse, and interaction estimation was infeasible for SMQs. Positive risk differences were observed in a limited number of estimable combinations for broad SMQs, but statistically robust positive interactions were scarce. While hypnotics and strong anticholinergic drugs may be associated with dementia and delirium, sparse concomitant exposure limits the assessment of interactions in JADER. Careful signal exploration and clinical validation are therefore warranted.