The efficacy and safety of Yokukansan for concomitant behavioral and psychological symptoms of Alzheimer's disease: a randomized, double-blinded clinical trial.

ETHNOPHARMACOLOGY RELEVANCE: Yokukansan (YKS), a traditional Japanese formula, relieves agitation, anxiety, and sleep disturbance and has demonstrated potential in alleviating behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). However, the evidence regarding its efficacy and safety remains limited. AIM OF THE STUDY: The paper assessed the effect of YKS on managing BPSD and cognition in AD compared to placebo. MATERIALS AND METHODS: This was a single-center, randomized, double-blinded, placebo-controlled trial performed between July 2023 and May 2024. A total of 100 subjects with AD and BPSD were registered. The YKS group received 2.5g of YKS thrice daily for 4 weeks; the placebo group received identical granules. Evaluations were conducted at baseline and at weeks 2, 4, and 8. The primary outcome was the change in Neuropsychiatric Inventory (NPI) scores from baseline to week 4. Secondary outcomes included the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Hamilton Depression Rating Scale (HAMD-17), and Liver Qi Stagnation and Spleen Qi Deficiency (LQSSQD). RESULTS: Of the 100 participants, 89 completed the trial. The mean reduction in NPI scores was more significant in the YKS group than in the Placebo group at week 4 (P < 0.05). YKS showed trends of improvement in ADCS-ADL and MMSE scores, but no significant cognitive or mood changes were observed at week 4. CONCLUSION: It was more effective than a placebo in reducing BPSD in AD patients, suggesting potential as an adjunct therapy. Larger studies are needed to confirm these results. CHINESE CLINICAL TRIAL REGISTRY: ChiCTR2300069404.