Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease

Katsutoshi Furukawa, Naoki Tomita, Daisuke Uematsu, Kazunori Okahara, Hiroyuki Shimada, Masaki Ikeda, Toshifumi Matsui, Koichi Kozaki, Masahiko Fujii, Tatsuji Ogawa, Hiroyuki Umegaki, Katsuya Urakami, Hiroshi Nomura, Naoto Kobayashi, Aki Nakanishi, Yukihiro Washimi, Hisashi Yonezawa, Satoshi Takahashi, Masaharu Kubota, Yosuke WakutaniDaisuke Ito, Takahiro Sasaki, Etsuro Matsubara, Kaori Une, Aiko Ishiki, Yukie Yahagi, Mikio Shoji, Hiroyasu Sato, Yasuo Terayama, Masafumi Kuzuya, Nobuo Araki, Manabu Kodama, Takuhiro Yamaguchi, Hiroyuki Arai

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Aim: 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 (7.5g/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.

Original languageEnglish
JournalGeriatrics and Gerontology International
DOIs
Publication statusAccepted/In press - 2015

Fingerprint

dementia
Multicenter Studies
Behavioral Symptoms
Alzheimer Disease
Placebos
Dementia
Psychology
Aggression
Outcome Assessment (Health Care)
aggression
examination
Herbal Medicine
Hallucinations
Traditional Medicine
Group
Nursing Homes
Yi-Gan San
traditional medicine
Randomized Controlled Trials
statistical significance

Keywords

  • Alzheimer's disease
  • Behavioral and psychological symptoms of dementia
  • Kampo medicine
  • Neuropsychiatric Inventory Brief Questionnaire Form
  • Yokukansan

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Gerontology
  • Health(social science)

Cite this

Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease. / Furukawa, Katsutoshi; Tomita, Naoki; Uematsu, Daisuke; Okahara, Kazunori; Shimada, Hiroyuki; Ikeda, Masaki; Matsui, Toshifumi; Kozaki, Koichi; Fujii, Masahiko; Ogawa, Tatsuji; Umegaki, Hiroyuki; Urakami, Katsuya; Nomura, Hiroshi; Kobayashi, Naoto; Nakanishi, Aki; Washimi, Yukihiro; Yonezawa, Hisashi; Takahashi, Satoshi; Kubota, Masaharu; Wakutani, Yosuke; Ito, Daisuke; Sasaki, Takahiro; Matsubara, Etsuro; Une, Kaori; Ishiki, Aiko; Yahagi, Yukie; Shoji, Mikio; Sato, Hiroyasu; Terayama, Yasuo; Kuzuya, Masafumi; Araki, Nobuo; Kodama, Manabu; Yamaguchi, Takuhiro; Arai, Hiroyuki.

In: Geriatrics and Gerontology International, 2015.

Research output: Contribution to journalArticle

Furukawa, K, Tomita, N, Uematsu, D, Okahara, K, Shimada, H, Ikeda, M, Matsui, T, Kozaki, K, Fujii, M, Ogawa, T, Umegaki, H, Urakami, K, Nomura, H, Kobayashi, N, Nakanishi, A, Washimi, Y, Yonezawa, H, Takahashi, S, Kubota, M, Wakutani, Y, Ito, D, Sasaki, T, Matsubara, E, Une, K, Ishiki, A, Yahagi, Y, Shoji, M, Sato, H, Terayama, Y, Kuzuya, M, Araki, N, Kodama, M, Yamaguchi, T & Arai, H 2015, 'Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease', Geriatrics and Gerontology International. https://doi.org/10.1111/ggi.12696
Furukawa, Katsutoshi ; Tomita, Naoki ; Uematsu, Daisuke ; Okahara, Kazunori ; Shimada, Hiroyuki ; Ikeda, Masaki ; Matsui, Toshifumi ; Kozaki, Koichi ; Fujii, Masahiko ; Ogawa, Tatsuji ; Umegaki, Hiroyuki ; Urakami, Katsuya ; Nomura, Hiroshi ; Kobayashi, Naoto ; Nakanishi, Aki ; Washimi, Yukihiro ; Yonezawa, Hisashi ; Takahashi, Satoshi ; Kubota, Masaharu ; Wakutani, Yosuke ; Ito, Daisuke ; Sasaki, Takahiro ; Matsubara, Etsuro ; Une, Kaori ; Ishiki, Aiko ; Yahagi, Yukie ; Shoji, Mikio ; Sato, Hiroyasu ; Terayama, Yasuo ; Kuzuya, Masafumi ; Araki, Nobuo ; Kodama, Manabu ; Yamaguchi, Takuhiro ; Arai, Hiroyuki. / Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease. In: Geriatrics and Gerontology International. 2015.
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abstract = "Aim: 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 (7.5g/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.",
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author = "Katsutoshi Furukawa and Naoki Tomita and Daisuke Uematsu and Kazunori Okahara and Hiroyuki Shimada and Masaki Ikeda and Toshifumi Matsui and Koichi Kozaki and Masahiko Fujii and Tatsuji Ogawa and Hiroyuki Umegaki and Katsuya Urakami and Hiroshi Nomura and Naoto Kobayashi and Aki Nakanishi and Yukihiro Washimi and Hisashi Yonezawa and Satoshi Takahashi and Masaharu Kubota and Yosuke Wakutani and Daisuke Ito and Takahiro Sasaki and Etsuro Matsubara and Kaori Une and Aiko Ishiki and Yukie Yahagi and Mikio Shoji and Hiroyasu Sato and Yasuo Terayama and Masafumi Kuzuya and Nobuo Araki and Manabu Kodama and Takuhiro Yamaguchi and Hiroyuki Arai",
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T1 - Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease

AU - Furukawa, Katsutoshi

AU - Tomita, Naoki

AU - Uematsu, Daisuke

AU - Okahara, Kazunori

AU - Shimada, Hiroyuki

AU - Ikeda, Masaki

AU - Matsui, Toshifumi

AU - Kozaki, Koichi

AU - Fujii, Masahiko

AU - Ogawa, Tatsuji

AU - Umegaki, Hiroyuki

AU - Urakami, Katsuya

AU - Nomura, Hiroshi

AU - Kobayashi, Naoto

AU - Nakanishi, Aki

AU - Washimi, Yukihiro

AU - Yonezawa, Hisashi

AU - Takahashi, Satoshi

AU - Kubota, Masaharu

AU - Wakutani, Yosuke

AU - Ito, Daisuke

AU - Sasaki, Takahiro

AU - Matsubara, Etsuro

AU - Une, Kaori

AU - Ishiki, Aiko

AU - Yahagi, Yukie

AU - Shoji, Mikio

AU - Sato, Hiroyasu

AU - Terayama, Yasuo

AU - Kuzuya, Masafumi

AU - Araki, Nobuo

AU - Kodama, Manabu

AU - Yamaguchi, Takuhiro

AU - Arai, Hiroyuki

PY - 2015

Y1 - 2015

N2 - Aim: 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 (7.5g/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.

AB - Aim: 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 (7.5g/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.

KW - Alzheimer's disease

KW - Behavioral and psychological symptoms of dementia

KW - Kampo medicine

KW - Neuropsychiatric Inventory Brief Questionnaire Form

KW - Yokukansan

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