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Randomized Controlled Trial
. 2017 Feb;27(1):52-65.
doi: 10.1089/cap.2016.0081.

The Treatment of Severe Childhood Aggression Study: 12 Weeks of Extended, Blinded Treatment in Clinical Responders

Robert L Findling  1   2 , Lisa Townsend  1   3 , Nicole V Brown  4 , L Eugene Arnold  5 , Kenneth D Gadow  6 , David J Kolko  7 , Nora K McNamara  8 , Devin S Gary  2 , Dana B Kaplin  1 , Cristan A Farmer  9 , Heidi Kipp  7 , Craig Williams  10 , Eric M Butter  11 , Oscar G Bukstein  12 , Robert Rice Jr  10 , Kristin Buchan-Page  10 , Brooke S G Molina  7 , Michael G Aman  10
Affiliations
Randomized Controlled Trial

The Treatment of Severe Childhood Aggression Study: 12 Weeks of Extended, Blinded Treatment in Clinical Responders

Robert L Findling et al. J Child Adolesc Psychopharmacol. 2017 Feb.

Abstract

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.

Keywords: aggression; clinical trial; disruptive behavior disorders; stimulant.

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Conflict of interest statement

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.

Figures

<b>FIG. 1.</b>
FIG. 1.
CONSORT diagram accounting for participants during the TOSCA Extension phase (weeks 9 through 21). TOSCA, Treatment of Severe Childhood Aggression.
<b>FIG. 2.</b>
FIG. 2.
Nisonger Child Behavior Rating Form Disruptive Behavior Total (D-Total) by Treatment Group (Augmented vs. Basic) over time for those in Extension.
<b>FIG. 3.</b>
FIG. 3.
LOCF at week 4 or later for all randomized subjects present at week 3 (n = 81 for Basic and 73 for Augmented). (a) NCBRF Disruptive Behavior Total (D-Total) Score as a function of treatment group (Augmented vs. Basic) over time. (b) NCBRF Positive Social Subscale Score as a function of treatment group (Augmented vs. Basic) over time. LOCF, last-observation-carried forward. Note: means and standard errors are shown.
See this image and copyright information in PMC

References

    1. Aman MG, Binder C, Turgay A: Risperidone effects in the presence of psychostimulant medicine in children with ADHD and disruptive behavior disorders. J Child Adolesc Psychopharmacol 14:243–254, 2004 - PubMed
    1. Aman MG, Bukstein OG, Gadow KD, Arnold L, Molina S, McNamara N, Rundberg-Rivera E, Li X, Kipp H, Schneider J, Butter E, Baker J, Sprafkin J, Rice R, Bangalore S, Farmer C, Austin A, Buchan-Page K, Brown N, Hurt E, Grondhuis S, Findling R: What does risperidone add to parent training and stimulant for severe aggression in child attention-deficit/hyperactivity disorder? J Am Acad Child Adolesc Psychiatry 53:47–60 e41, 2014 - PMC - PubMed
    1. Aman M, Leone S, Lecavalier L, Park L, Buican B, Coury D: The Nisonger Child Behavior Rating Form: Typical IQ version. Int Clin Psychopharmacol 23:232–242, 2008 - PubMed
    1. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association; 1994
    1. Arnold LE, Chuang S, Davies M, Abikoff HB, Conners CK, Elliott GR, Greenhill LL, Hechtman L, Hinshaw SP, Hoza B, Jensen PS, Kraemer HC, Langworthy-Lam KS, March JS, Newcorn JH, Pelham WE, Severe JB, Swanson JM, Vitiello B, Wells KC, Wigal T: Nine months of multicomponent behavioral treatment for ADHD and effectiveness of MTA fading procedures. J Abnorm Child Psychol 32:39–51, 2004 - PubMed

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