title: Yokukansan (TJ-54) for treatment of pervasive developmental disorder not otherwise specified and Asperger's disorder: a 12-week prospective, open-label study.
abstract: BACKGROUND
  Numerous medications have been tested on patients with pervasive developmental disorder not otherwise specified (PDD-NOS) and Asperger's disorder. Although many of these medications have been demonstrated to be useful, no clear primary treatment for PDD-NOS and Asperger's disorder has emerged. Despite the efficacy of some of the medicines, the acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Japanese herbal medicine yokukansan (TJ-54) may be safe and useful in treating behavioral and psychological symptoms in dementia and some neuropsychiatric disorders. We aimed at evaluating both the efficacy and safety of TJ-54 in patients with well-defined PDD-NOS and Asperger's disorder.
  
  
  METHODS
  This was a 12-week prospective, open-label investigation of TJ-54 in 40 children, adolescents, and adults diagnosed with PDD-NOS or Asperger's disorder. Primary outcome measures included the Clinical Global Impressions-Severity of Illness Scale (CGI-S) and the Aberrant Behavior Checklist-Iritability subscale score (ABC-I).
  
  
  RESULTS
  Forty subjects, ages 8-40 years (mean 22.7 ± 7.3 years) received a mean final TJ-54 dosage of 6.4 ± 1.3 g/day (range 2.5-7.5 g/day). Full-scale intelligence quotient (IQ) scores ranged from 70 to 110 (mean 88.9 ± 13.2). Thirty-six (90%) of 40 subjects showed fewer interfering symptoms of irritability, including aggression, self-injury, and tantrums, with a final CGI-S of 1 or 2 (normal, not at all ill or borderline mentally ill) and a 80% or greater improvement on the ABC-I. The mean CGI-S score at baseline was 6.8 ± 0.8 whereas scores at end point was 1.9 ± 0.1 (< 0.0001). ABC-I scores ranged from 11 to 29 (mean 17.4 ± 3.66) at baseline, whereas scores at week 12 ranged from 0 to 5 (mean 0.93 ± 0.97) (p <0.0001). TJ-54 was well tolerated. No subject exited the study due to a drug-related adverse event.
  
  
  CONCLUSIONS
  These preliminary data suggest that TJ-54 may be effective and well tolerated for treatment of severe irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech in patients with PDD-NOS or Asperger's disorder. However, given the characteristics of this trial, the present findings should be taken cautiously, and larger-scale placebo-controlled studies are needed to elucidate the efficacy and tolerability of TJ-54 in this understudied population.
authors.affiliation: Department of Psychiatry, Shimane University School of Medicine, 89-1 Enyacho, Izumo 693-8501, Japan. miyanyan@med.shimane-u.ac.j
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyaoka
authors.forename: Rei
authors.initials: R
authors.lastname: Wake
authors.forename: Motohide
authors.initials: M
authors.lastname: Furuya
authors.forename: Kristian
authors.initials: K
authors.lastname: Liaury
authors.forename: Masa
authors.initials: M
authors.lastname: Ieda
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawakami
authors.forename: Keiko
authors.initials: K
authors.lastname: Tsuchie
authors.forename: Takuji
authors.initials: T
authors.lastname: Inagaki
authors.forename: Jun
authors.initials: J
authors.lastname: Horiguchi
mesh_terms: D000293:Adolescent; D000328:Adult; D020817:Asperger Syndrome / Q000188:drug therapy*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004365:Drugs, Chinese Herbal; C524644:Yi-Gan San