Affiliations: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
Correspondence:
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Correspondence to: Shinji Matsunaga, MD, PhD, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. Tel.: +81 562 93 9250; Fax: +81 562 93 1831; E-mail: shinjim@fujita-hu.ac.jp and Taro Kishi, MD, PhD, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. Tel.: +81 562 93 9250; Fax: +81 562 93 1831; E-mail: tarok@fujita-hu.ac.jp.
Abstract: 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, I2 = 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.
Keywords: Alzheimer’s disease, behavioral and psychological symptoms of dementia, dementia, meta-analysis, yokukansan
