Abstract
BACKGROUND: Cholinesterase inhibitors (ChEIs) are recognized as first-line therapies for patients with mild-to-moderate dementia. However, there is limited comparative evidence regarding antipsychotic initiation risk among individual ChEIs to manage behavioral symptoms of dementia. OBJECTIVE: This study aims to evaluate and compare the risk of antipsychotic initiation among dementia patients prescribed individual ChEIs. METHODS: This is a retrospective cohort study using the 2009-2018 TriNetX electronic medical records data. Dementia patients aged over 60 years who were incident users of rivastigmine, donepezil, or galantamine with a 12-month washout period were included. Patients with a history of antipsychotic use during baseline and 30 days post-initiation of ChEIs were excluded. Patients were followed up to 12 months to identify the antipsychotic use. A generalized boosted model-based inverse probability treatment weights-adjusted Cox Proportional Hazard (CPH) model was applied to compare the risk of antipsychotic initiation across the different ChEIs. RESULTS: Among the 7,878 eligible dementia patients initiating ChEIs, 89.40% (n=7,043) were incident donepezil users, followed by 8.13% of (n=641) rivastigmine users, and 2.46% (n=194) galantamine users. During the 12-month follow-up, 807 patients (10.24%) initiated antipsychotics. The CPH model showed that rivastigmine users were at an increased risk of antipsychotic use compared to donepezil users (adjusted hazard ratio=1.45, 95% confidence interval: 1.11-1.88). No significant difference was observed in the risk of antipsychotic initiation between galantamine and donepezil users. CONCLUSION: This study found that rivastigmine users were more likely to initiate antipsychotics compared to donepezil users, while no significant difference between galantamine and donepezil users was observed. These findings emphasize the importance of careful medication monitoring and management to prevent prescribing cascades and reduce related adverse effects in dementia patients.