PMID- 24923986
OWN - NLM
STAT- MEDLINE
DCOM- 20151016
LR  - 20211021
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 232
IP  - 1
DP  - 2015 Jan
TI  - Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a 
      randomized, double-blind, placebo-controlled trial (a Positive and Negative 
      Syndrome Scale, five-factor analysis).
PG  - 155-64
LID - 10.1007/s00213-014-3645-8 [doi]
AB  - BACKGROUND: Treating schizophrenia patients who fail to respond to antipsychotics 
      is a major challenge, and the percentage of treatment-resistant patients is 
      estimated to be 20-25 %. Recent studies indicate that yokukansan (YKS; D2 and 
      5HT1A partial agonist and 5HT2A and glutamate antagonist) to be safe and useful 
      in treating behavioral and psychological symptoms associated with dementia and 
      other neuropsychiatric conditions. We aimed at evaluating both the efficacy and 
      safety of YKS in patients with treatment-resistant schizophrenia. METHODS: This 
      randomized, multicenter, double-blind, placebo-controlled study was conducted 
      between May 2010 and August 2012. One hundred twenty antipsychotic-treated 
      inpatients from 34 psychiatric hospitals in Japan were included. Patients were 
      randomized to adjuvant treatment with YKS 7.5 g/day or placebo. During a 4-week 
      follow-up, psychopathology was assessed using the Positive and Negative Syndrome 
      Scale (PANSS) with five factors [excitement/hostility (P4, P7, G8, and G14), 
      depression/anxiety (G1, G2, G3, G4, and G6), cognition (P2, N5, N7, G5, G10, G11, 
      G12, G13, and G15], positive (P1, P3, P5, P6, and G9), and negative (N1, N2, N3, 
      N4, N6, G7, and G16]]. Other assessments included, Clinical Global 
      Impression-Severity (CGI-S), Global Assessment of Functioning (GAF), and 
      Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The primary efficacy outcome 
      was the change in PANSS five-factor scores. The secondary outcomes were changes 
      in the scores of CGI-S. The analysis was made on a modified intention to treat 
      basis with the help of a last observation carried forward method. RESULTS: YKS 
      showed a tendency of superiority to placebo in reducing total all PANSS 
      five-factor scores in treatment-resistant schizophrenia, but the difference was 
      not statistically significant in total, depression/anxiety, cognition, positive, 
      and negative factors. However, compared to the placebo group, the YKS group 
      showed statistically significant improvements in the PANSS excitement/hostility 
      factor scores (p<0.05). No substantial side effects were recorded. CONCLUSION: 
      The results of the present study indicate YKS to be a potential adjunctive 
      treatment strategy for treatment-resistant schizophrenia, particularly to improve 
      excitement/hostility symptoms.
FAU - Miyaoka, Tsuyoshi
AU  - Miyaoka T
AD  - Department of Psychiatry, Shimane University School of Medicine, Izumo, Japan, 
      miyanyan@med.shimane-u.ac.jp.
FAU - Furuya, Motohide
AU  - Furuya M
FAU - Horiguchi, Jun
AU  - Horiguchi J
FAU - Wake, Rei
AU  - Wake R
FAU - Hashioka, Sadayuki
AU  - Hashioka S
FAU - Tohyama, Masaya
AU  - Tohyama M
FAU - Mori, Norio
AU  - Mori N
FAU - Minabe, Yoshio
AU  - Minabe Y
FAU - Iyo, Masaomi
AU  - Iyo M
FAU - Ueno, Shyuichi
AU  - Ueno S
FAU - Ezoe, Sachiko
AU  - Ezoe S
FAU - Murotani, Kenta
AU  - Murotani K
FAU - Hoshino, Syuzo
AU  - Hoshino S
FAU - Seno, Haruo
AU  - Seno H
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140613
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Yi-Gan San)
SB  - IM
MH  - Adult
MH  - Antipsychotic Agents/adverse effects/*therapeutic use
MH  - Double-Blind Method
MH  - Drugs, Chinese Herbal/adverse effects/*therapeutic use
MH  - Factor Analysis, Statistical
MH  - Female
MH  - Follow-Up Studies
MH  - Gastrointestinal Diseases/chemically induced/epidemiology
MH  - Humans
MH  - Japan/epidemiology
MH  - Male
MH  - Middle Aged
MH  - *Psychiatric Status Rating Scales/statistics & numerical data
MH  - Schizophrenia/diagnosis/*drug therapy/epidemiology
EDAT- 2014/06/14 06:00
MHDA- 2015/10/17 06:00
CRDT- 2014/06/14 06:00
PHST- 2013/09/03 00:00 [received]
PHST- 2014/05/30 00:00 [accepted]
PHST- 2014/06/14 06:00 [entrez]
PHST- 2014/06/14 06:00 [pubmed]
PHST- 2015/10/17 06:00 [medline]
AID - 10.1007/s00213-014-3645-8 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2015 Jan;232(1):155-64. doi: 
      10.1007/s00213-014-3645-8. Epub 2014 Jun 13.