Yokukansan in the Treatment of Behavioral and Psychological Symptoms of Dementia: An Updated Meta-Analysis of Randomized Controlled Trials

Background: Previous clinical studies found that yokukansan has a therapeutic effect on behavioral and psychological symptoms of dementia (BPSD) in dementia patients. Objective: To perform an updated meta-analysis of randomized controlled trials (RCTs) testing yokukansan for patients with BPSD. Methods: Primary efficacy and safety endpoints were BPSD total scores and all-cause discontinuation, respectively. Secondary outcomes were BPSD subscales, cognitive function scores [Mini-mental state examination (MMSE)], activities of daily living (ADL) scores, discontinuation due to adverse events (AEs), and incidences of AEs. Results: Five RCTs with 381 patients with BPSD were included. Compared with controls [placebo+ usual care (UC)], yokukansan significantly decreased BPSD total scores [standardized mean difference (SMD) = -0.32, 95% confidence interval (CI) = - 0.53 to -0.11, p = 0.003, I-2 = 0%, N= 5 studies, n = 361]. Yokukansan was more efficacious in reducing BPSD subscale scores (delusions: SMD=-0.51, 95% CI = -0.98 to -0.04, hallucinations: SMD= -0.54, 95% CI = -0.96 to -0.12, agitation/aggression: SMD=- 0.37, 95% CI = -0.60 to -0.15) than placebo+UC. However, yokukansan was not superior to placebo+UC for BPSD total as well as any subscales scores only in Alzheimer's disease patients. Compared with UC, yokukansan treatment improved ADL scores (SMD = -0.32, 95% CI = -0.62 to -0.01). MMSE scores did not differ between the yokukansan and placebo+UC treatment groups. No significant differences were found in all-cause discontinuation, discontinuation due to AEs, and incidences of AEs between yokukansan and placebo+UC treatments. Conclusions: Our results suggest that yokukansan is beneficial for the treatment of patients with BPSD and is well-tolerated; it was not beneficial for BPSD total and any subscale scores only in Alzheimer's disease patients.