title: 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).
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Shimane University School of Medicine, Izumo, Japan, miyanyan@med.shimane-u.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyaoka
authors.forename: Motohide
authors.initials: M
authors.lastname: Furuya
authors.forename: Jun
authors.initials: J
authors.lastname: Horiguchi
authors.forename: Rei
authors.initials: R
authors.lastname: Wake
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Hashioka
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Minabe
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Shyuichi
authors.initials: S
authors.lastname: Ueno
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ezoe
authors.forename: Kenta
authors.initials: K
authors.lastname: Murotani
authors.forename: Syuzo
authors.initials: S
authors.lastname: Hoshino
authors.forename: Haruo
authors.initials: H
authors.lastname: Seno
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000627:therapeutic use*; D005163:Factor Analysis, Statistical; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D014150:Antipsychotic Agents; D004365:Drugs, Chinese Herbal; C524644:Yi-Gan San