Efficacy and safety of Woohwangchungsimwon in combination with donepezil for behavioral and psychological symptoms of dementia in probable Alzheimer's disease: An assessor-blinded randomized controlled trial

Background: Woohwangchungsimwon (WCW) is a traditional Korean herbal formula commonly used to treat anxiety and restlessness. However, its potential role in managing behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD) is unclear. Objective: This study evaluated the efficacy and safety of WCW as an adjunctive treatment for BPSD in patients with mild probable AD already receiving donepezil. Methods: Seventy-four patients receiving donepezil 5 mg daily were randomized 1:1 into an intervention group (WCW add-on, n = 37) or a control group (no additional treatment, n = 37) for 24 weeks. The primary outcome was the change in BPSD measured using the Neuropsychiatric Inventory (NPI). Secondary outcomes were cognitive function and emotional and physical well-being, including depression, anxiety, insomnia, quality of life, and severity of dementia. Safety was assessed via adverse events and laboratory results. Results: Sixty-three participants were included. The WCW group demonstrated significantly improved total NPI scores versus controls, particularly in the irritability/lability subdomain. Analysis of covariance (ANCOVA) confirmed these findings in both the full analysis set (FAS) and per-protocol set (PPS). T-test and rank ANCOVA showed significance in the PPS and a trend in the FAS. The general quality of life dementia scale showed a trend toward improvement. No significant differences in adverse events or laboratory results were observed. Conclusions: WCW may be a safe and effective adjunctive therapy for BPSD in patients with mild probable AD. Future studies should adopt more rigorous designs and include patients with broader disease severity to enhance clinical applicability. Trial registration: The trial was registered with the Clinical Research Information Service (CRIS) on December 10, 2020 (KCT0005669).