title: Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease.
abstract: OBJECTIVE
  Yokukansan (YKS), a traditional herbal medicine, has been used to treat behavioral and psychological symptoms of dementia (BPSD). The present study is the first double-blind, randomized, placebo-controlled trial to determine the efficacy and safety of YKS for the treatment of BPSD in Alzheimer's disease (AD).
  
  
  METHODS
  A total of 22 sites consisting of clinics, hospitals and nursing homes participated. A total of 145 patients with AD were randomized. Active YKS (7.5 g/day) and placebo were supplied to 75 and 70 participants, respectively. The primary outcome measure was the 4-week change in total score of the Neuropsychiatric Inventory Brief Questionnaire Form (NPI-Q), an instrument that evaluates BPSD. Secondary outcome measures included 12-week changes in NPI-Q scores, changes in NPI-Q subcategory scores and total scores of the Mini-Mental-State Examination.
  
  
  RESULTS
  Four-week changes in NPI-Q total scores did not differ significantly between the treatment and placebo groups. There were also no significant differences between groups in 12-week changes in total NPI-Q scores, NPI-Q subcategory scores or total Mini-Mental-State Examination scores. However, a subgroup with fewer than 20 points on the Mini-Mental-State Examination at baseline showed a greater decrease in "agitation/aggression" score in the YKS group than in the placebo group (P = 0.007). No serious adverse effects were observed during the study.
  
  
  CONCLUSIONS
  Our data did not reach statistical significance regarding the efficacy of YKS against BPSD; however, YKS improves some symptoms including "agitation/aggression" and "hallucinations" with low frequencies of adverse events. Geriatr Gerontol Int 2017; 17: 211-218.
authors.affiliation: Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer Tohoku University, Sendai, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer Tohoku University, Sendai, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tomita
authors.affiliation: Uematsu Neurological Clinic, Saitama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Uematsu
authors.affiliation: Keimei Memorial Hospital, Kunitomi, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Okahara
authors.affiliation: Department of Geriatrics and Neurology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Geriatric Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kozaki
authors.affiliation: Yamagata Kousei Hospital, Yamagata, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Aoba Neurosurgical Clinic, Sendai, Japan.
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Ogawa
authors.affiliation: Department of Community Healthcare & Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Umegaki
authors.affiliation: Department of Biological Regulation, School of Health Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Urakami
authors.affiliation: Hiroshi Nomura Neurology Clinic, Sendai, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nomura
authors.affiliation: Azuma Street Clinic, Fukushima, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Department of Neurology and Psychiatry, Osaka City Kousaiin Hospital, Suita, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Nakanishi
authors.affiliation: Department of Cognitive Disorders, National Center for Geriatrics and Gerontology, Obu, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Washimi
authors.affiliation: Department of Neurology, Iwate Medical University, Morioka, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yonezawa
authors.affiliation: Department of Neurology, Iwate Medical University, Morioka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Kusakabe Memorial Hospital, Yamanashi, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Neurology, Kurashiki Heisei Hospital, Kurashiki, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Wakutani
authors.affiliation: Department of Neurology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ito
authors.affiliation: Department of Neurology, School of Medicine, Saitama Medical University, Moroyama, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Neurology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Yufu, Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Matsubara
authors.affiliation: Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer Tohoku University, Sendai, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Une
authors.affiliation: Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer Tohoku University, Sendai, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Ishiki
authors.affiliation: Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yahagi
authors.affiliation: Department of Neurology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Yufu, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.affiliation: Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Neurology, Iwate Medical University, Morioka, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terayama
authors.affiliation: Department of Community Healthcare & Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kuzuya
authors.affiliation: Department of Neurology, School of Medicine, Saitama Medical University, Moroyama, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Araki
authors.affiliation: Kodama Hospital, Ishinomaki, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kodama
authors.affiliation: Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer Tohoku University, Sendai, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000523:psychology*; D001526:Behavioral Symptoms / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000209:etiology; D009483:Neuropsychological Tests; D008517:Phytotherapy
chemical_list: D004365:Drugs, Chinese Herbal; C524644:Yi-Gan San
keywords: Alzheimer's disease; Kampo medicine; Neuropsychiatric Inventory Brief Questionnaire Form; Yokukansan; behavioral and psychological symptoms of dementia