Analysis of Adverse Events of Cholinesterase Inhibitors and NMDA Receptor Antagonists on Arrhythmias Using the Japanese Adverse Drug Event Report Database

Background: The association between anti-dementia drugs and arrhythmia is uncertain. In addition, the effects of certain drug combinations are not yet well known.

Objective: We investigated the association between anti-dementia drugs and arrhythmia. Furthermore, we investigated the effects of anti-dementia drugs both alone and in combination on the likelihood of arrhythmia in patients with dementia.

Methods: We examined the Japanese Adverse Drug Event Report database (JADER) from April 2004 to May 2022 for dementia drug users aged ≥ 60 years. We calculated the unadjusted reported odds ratio (ROR) and adjusted ROR for confounding factors. Furthermore, we examined the association of various combinations of anti-dementia drugs with the development of arrhythmias.

Results: There were 6718 arrhythmia cases identified out of 333,702 reported cases. The unadjusted ROR results were as follows: donepezil alone (ROR 4.39, 95% confidence interval [CI] 3.89-4.95), rivastigmine alone (2.10, 1.53-2.87), galantamine alone (3.87, 3.04-4.94), memantine alone (2.25, 1.59-3.20), and combination of choline esterase inhibitor and memantine (2.56, 1.84-3.57). In a multivariate analysis, the RORs remained significant.

Conclusions: Regardless of whether anti-dementia drugs were used alone or in combination, attention should be paid to the occurrence of arrhythmias.