PMID- 28212067
OWN - NLM
STAT- MEDLINE
DCOM- 20180111
LR  - 20181113
IS  - 1557-8992 (Electronic)
IS  - 1044-5463 (Print)
IS  - 1044-5463 (Linking)
VI  - 27
IP  - 1
DP  - 2017 Feb
TI  - The Treatment of Severe Childhood Aggression Study: 12 Weeks of Extended, Blinded 
      Treatment in Clinical Responders.
PG  - 52-65
LID - 10.1089/cap.2016.0081 [doi]
AB  - OBJECTIVES: 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. METHODS: 
      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). RESULTS: 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). 
      CONCLUSIONS: 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.
FAU - Findling, Robert L
AU  - Findling RL
AD  - 1 Division of Child and Adolescent Psychiatry, Johns Hopkins University , 
      Baltimore, Maryland.
AD  - 2 Department of Psychiatry, Kennedy Krieger Institute , Baltimore, Maryland.
FAU - Townsend, Lisa
AU  - Townsend L
AD  - 1 Division of Child and Adolescent Psychiatry, Johns Hopkins University , 
      Baltimore, Maryland.
AD  - 3 Department of Mental Health, Johns Hopkins Bloomberg School of Public Health , 
      Baltimore, Maryland.
FAU - Brown, Nicole V
AU  - Brown NV
AD  - 4 Center for Biostatistics, Ohio State University Medical Center , Columbus, 
      Ohio.
FAU - Arnold, L Eugene
AU  - Arnold LE
AD  - 5 Department of Psychiatry, Ohio State University , Columbus, Ohio.
FAU - Gadow, Kenneth D
AU  - Gadow KD
AD  - 6 Department of Psychiatry, Stony Brook University , Stony Brook, New York.
FAU - Kolko, David J
AU  - Kolko DJ
AD  - 7 Department of Psychiatry and Psychology, University of Pittsburgh School of 
      Medicine , Pittsburgh, Pennsylvania.
FAU - McNamara, Nora K
AU  - McNamara NK
AD  - 8 Department of Psychiatry, Case Western Reserve University , Cleveland, Ohio.
FAU - Gary, Devin S
AU  - Gary DS
AD  - 2 Department of Psychiatry, Kennedy Krieger Institute , Baltimore, Maryland.
FAU - Kaplin, Dana B
AU  - Kaplin DB
AD  - 1 Division of Child and Adolescent Psychiatry, Johns Hopkins University , 
      Baltimore, Maryland.
FAU - Farmer, Cristan A
AU  - Farmer CA
AD  - 9 Pediatrics & Developmental Neuroscience Branch, National Institute of Mental 
      Health , Bethesda, Maryland.
FAU - Kipp, Heidi
AU  - Kipp H
AD  - 7 Department of Psychiatry and Psychology, University of Pittsburgh School of 
      Medicine , Pittsburgh, Pennsylvania.
FAU - Williams, Craig
AU  - Williams C
AD  - 10 The Nisonger Center (UCEDD), Ohio State University , Columbus, Ohio.
FAU - Butter, Eric M
AU  - Butter EM
AD  - 11 Division of Pediatric Psychology and Neuropsychology, Nationwide Children's 
      Hospital , Columbus, Ohio.
FAU - Bukstein, Oscar G
AU  - Bukstein OG
AD  - 12 Harvard University Children's Hospital , Boston, Massachusetts.
FAU - Rice, Robert Jr
AU  - Rice R Jr
AD  - 10 The Nisonger Center (UCEDD), Ohio State University , Columbus, Ohio.
FAU - Buchan-Page, Kristin
AU  - Buchan-Page K
AD  - 10 The Nisonger Center (UCEDD), Ohio State University , Columbus, Ohio.
FAU - Molina, Brooke S G
AU  - Molina BS
AD  - 7 Department of Psychiatry and Psychology, University of Pittsburgh School of 
      Medicine , Pittsburgh, Pennsylvania.
FAU - Aman, Michael G
AU  - Aman MG
AD  - 10 The Nisonger Center (UCEDD), Ohio State University , Columbus, Ohio.
LA  - eng
GR  - R01 MH077907/MH/NIMH NIH HHS/United States
GR  - R01 MH077750/MH/NIMH NIH HHS/United States
GR  - R01 MH077676/MH/NIMH NIH HHS/United States
GR  - R01 MH077997/MH/NIMH NIH HHS/United States
GR  - M01 RR010710/RR/NCRR NIH HHS/United States
GR  - UL1 RR024153/RR/NCRR NIH HHS/United States
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Child Adolesc Psychopharmacol
JT  - Journal of child and adolescent psychopharmacology
JID - 9105358
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Central Nervous System Stimulants)
RN  - L6UH7ZF8HC (Risperidone)
SB  - IM
MH  - Aggression/*drug effects/psychology
MH  - Antipsychotic Agents/administration & dosage/therapeutic use
MH  - Attention Deficit Disorder with Hyperactivity/*drug therapy/psychology
MH  - Central Nervous System Stimulants/*administration & dosage/therapeutic use
MH  - Child
MH  - Combined Modality Therapy
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Parents/education
MH  - Psychiatric Status Rating Scales
MH  - Risperidone/*administration & dosage/therapeutic use
MH  - Severity of Illness Index
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC5327034
OTO - NOTNLM
OT  - aggression
OT  - clinical trial
OT  - disruptive behavior disorders
OT  - stimulant
COIS- Dr. Findling receives or has received research support, acted as a consultant, 
      and/or served on a speaker's bureau for Alcobra, American Academy of Child & 
      Adolescent Psychiatry, American Physician Institute, American Psychiatric Press, 
      Bracket, CogCubed, Cognition Group, Coronado Biosciences, Dana Foundation, 
      Elsevier, Forest, Guilford Press, Ironshore, Johns Hopkins University Press, 
      Jubilant Clinsys, KemPharm, Lundbeck, Merck, NIH, Neurim, Novartis, Otsuka, 
      Oxford University Press, Pfizer, Physicians Postgraduate Press, Purdue, Rhodes 
      Pharmaceuticals, Roche, Sage, Shire, Sunovion, Supernus Pharmaceuticals, 
      Transcept Pharmaceuticals, Tris, Validus, and WebMD. Dr. Arnold has received 
      research funding from Curemark, Forest, Lilly, Neuropharm, Novartis, Noven, 
      Shire, and Young Living (as well as NIH and Autism Speaks) and has consulted with 
      or been on advisory boards for Arbor, Gowlings, Neuropharm, Novartis, Noven, 
      Organon, Otsuka, Pfizer, Roche, Seaside Therapeutics, Sigma Tau, Shire, Tris 
      Pharma, and Waypoint and received travel support from Noven. Dr. Gadow is 
      shareholder in Checkmate Plus, publisher of the Child and Adolescent Symptom 
      Inventory-4R. Dr. Kolko has received research funds from the NIMH and SAMHSA. Dr. 
      Butter has received funding from NIMH, MCHB/HRSA, Autism Speaks, and the Simons 
      Foundation and is board member of the RUBI Foundation, a 501(C)3 organization 
      supporting autism treatment research. Dr. Bukstein has acted as a consultant 
      and/or served on a speaker's bureau or received royalties from Cephalon, Forest, 
      Lilly, Novartis, Shire, Johnson and Johnson, and Routledge Press. Dr. Aman has 
      received research contracts, consulted with, served on advisory boards, or done 
      investigator training for BioMarin Pharmaceutical, Bristol-Myers Squibb, 
      Cogstate, Inc., Confluence Pharmaceuticals, Cogstate Clinical Trials, Ltd., 
      Coronado Biosciences, Forest Research, Hoffman LaRoche, Johnson and Johnson, 
      MedAvante, Inc., Novartis, Pfizer, ProPhase LLC, and Supernus Pharmaceuticals. 
      Lisa Townsend, Nicole Brown, Nora McNamara, Devin Gary, Dana Kaplin, Cristan 
      Farmer, Heidi Kipp, Craig Williams, Robert Rice, Kristin Buchan-Page, and Brooke 
      Molina do not have any disclosures.
EDAT- 2017/02/18 06:00
MHDA- 2018/01/13 06:00
PMCR- 2018/02/01
CRDT- 2017/02/18 06:00
PHST- 2017/02/18 06:00 [entrez]
PHST- 2017/02/18 06:00 [pubmed]
PHST- 2018/01/13 06:00 [medline]
PHST- 2018/02/01 00:00 [pmc-release]
AID - 10.1089/cap.2016.0081 [pii]
AID - 10.1089/cap.2016.0081 [doi]
PST - ppublish
SO  - J Child Adolesc Psychopharmacol. 2017 Feb;27(1):52-65. doi: 
      10.1089/cap.2016.0081.