title: The Treatment of Severe Childhood Aggression Study: 12 Weeks of Extended, Blinded Treatment in Clinical Responders.
abstract: Previous "Treatment of Severe Childhood Aggression" (TOSCA) reports demonstrated that many children with severe physical aggression and attention-deficit/hyperactivity disorder (ADHD) responded well to two randomized treatments (parent training [PT]+stimulant+placebo = Basic vs. PT+stimulant+risperidone = Augmented) for 9 weeks. An important clinical question is whether these favorable outcomes are maintained over longer times.
  
  
  
  Clinical responders to the 9-week trial (n = 103/168), defined as Clinical Global Impressions (CGI)-Improvement of much/very much improved plus substantial reduction in parent ratings of disruptiveness, were followed another 12 weeks (21 weeks total) while remaining on blinded treatment. Outcome measures included Clinical Global Impressions scale, Nisonger Child Behavior Rating Form (NCBRF), other parent/teacher-rated scales, laboratory tests, clinician ratings of abnormal movement, and other adverse events (AEs).
  
  
  
  Parent ratings of problem behavior showed minimal worsening of behavior from end of the 9-week acute trial (expected from regression to the mean after selecting best responders), but outcomes at Extension endpoint were meaningfully improved compared with acute study baseline. As expected, outcomes for Basic and Augmented treatment did not differ among these children selected for good clinical response. During Extension, more Augmented subjects had elevated prolactin; there were no clinically confirmed cases of tardive dyskinesia. Delayed sleep onset was the most frequent Basic AE. We also conducted a last-observation-carried-forward analysis, which included both nonresponders and responders. We found that, at the end of Extension, Augmented subjects had more improvement than Basic subjects on the NCBRF Positive Social subscale (p = 0.005; d = 0.44), the Antisocial Behavior Scale Reactive Aggression subscale (p = 0.03; d = 0.36), and marginally so on the Disruptive Behavior Total subscale (p = 0.058; d = 0.29, the primary outcome).
  
  
  
  The medium-term outcomes were good for the participants in both treatment groups, perhaps because they were selected for good response. When nonresponders were included in ITT analyses, there was some indication that Augmented surpassed Basic treatment.
authors.affiliation: 1 Division of Child and Adolescent Psychiatry, Johns Hopkins University , Baltimore, Maryland.|2 Department of Psychiatry, Kennedy Krieger Institute , Baltimore, Maryland.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.affiliation: 1 Division of Child and Adolescent Psychiatry, Johns Hopkins University , Baltimore, Maryland.|3 Department of Mental Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Townsend
authors.affiliation: 4 Center for Biostatistics, Ohio State University Medical Center , Columbus, Ohio.
authors.forename: Nicole V
authors.initials: NV
authors.lastname: Brown
authors.affiliation: 5 Department of Psychiatry, Ohio State University , Columbus, Ohio.
authors.forename: L Eugene
authors.initials: LE
authors.lastname: Arnold
authors.affiliation: 6 Department of Psychiatry, Stony Brook University , Stony Brook, New York.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Gadow
authors.affiliation: 7 Department of Psychiatry and Psychology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kolko
authors.affiliation: 8 Department of Psychiatry, Case Western Reserve University , Cleveland, Ohio.
authors.forename: Nora K
authors.initials: NK
authors.lastname: McNamara
authors.affiliation: 2 Department of Psychiatry, Kennedy Krieger Institute , Baltimore, Maryland.
authors.forename: Devin S
authors.initials: DS
authors.lastname: Gary
authors.affiliation: 1 Division of Child and Adolescent Psychiatry, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Dana B
authors.initials: DB
authors.lastname: Kaplin
authors.affiliation: 9 Pediatrics & Developmental Neuroscience Branch, National Institute of Mental Health , Bethesda, Maryland.
authors.forename: Cristan A
authors.initials: CA
authors.lastname: Farmer
authors.affiliation: 7 Department of Psychiatry and Psychology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Heidi
authors.initials: H
authors.lastname: Kipp
authors.affiliation: 10 The Nisonger Center (UCEDD), Ohio State University , Columbus, Ohio.
authors.forename: Craig
authors.initials: C
authors.lastname: Williams
authors.affiliation: 11 Division of Pediatric Psychology and Neuropsychology, Nationwide Children's Hospital , Columbus, Ohio.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Butter
authors.affiliation: 12 Harvard University Children's Hospital , Boston, Massachusetts.
authors.forename: Oscar G
authors.initials: OG
authors.lastname: Bukstein
authors.affiliation: 10 The Nisonger Center (UCEDD), Ohio State University , Columbus, Ohio.
authors.forename: Robert
authors.initials: R
authors.lastname: Rice
authors.affiliation: 10 The Nisonger Center (UCEDD), Ohio State University , Columbus, Ohio.
authors.forename: Kristin
authors.initials: K
authors.lastname: Buchan-Page
authors.affiliation: 7 Department of Psychiatry and Psychology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Brooke S G
authors.initials: BS
authors.lastname: Molina
authors.affiliation: 10 The Nisonger Center (UCEDD), Ohio State University , Columbus, Ohio.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Aman
mesh_terms: D000374:Aggression / Q000187:drug effects* / Q000523:psychology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000627:therapeutic use; D002648:Child; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010290:Parents / Q000193:education; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000008:administration & dosage* / Q000627:therapeutic use; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D018967:Risperidone
keywords: aggression; clinical trial; disruptive behavior disorders; stimulant