What Does Risperidone Add to Stimulant and Parent Training for Severe Aggression in Child Attention-Deficit / Hyperactivity Disorder ?

Objective—Although combination pharmacotherapy is common in child/adolescent psychiatry, there has been little research evaluating it. We tested the value of adding risperidone to concurrent © 2013 American Academy of Child & Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved. Correspondence to Michael G. Aman, Ph.D., The Nisonger Center UCEDD, Ohio State University, 1581, Dodd Drive, Columbus, OH 43210-1296; aman.1@osu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosure: Dr. Aman has received research contracts, consulted with, or served on advisory boards of Biomarin Pharmaceuticals, Bristol-Myers Squibb, CogState, Confluence Pharmaceutica, Coronado Biosciences, Forest Research, Hoffman LaRoche, Johnson and Johnson, Novartis, and Supernus Pharmaceutica. Dr. Bukstein has received royalties from Routledge Press and acted as a consultant for Ezra Innovations and PRIME CME. Dr. Arnold has received research funding from CureMark, Forest, Lilly, and Shire; advisory board honoraria from Biomarin, Novartis, Noven, Roche, Seaside Therapeutics, and Shire; consulting fees from Tris Pharma; and travel support from Noven. Dr. McNamara has received research support from Forest Research, GlaxoSmithKline, Eli Lilly and Co., Lundbeck, Merck, NIH, Novartis, Otsuka, Pfizer, Rhodes Pharmaceuticals, Roche, Shire, Stanley Medical Research Institute, Sunovion, and Supernus Pharmaceuticals. Dr. Rundberg-Rivera has received research support from GlaxoSmithKline, Merck/ Schering Plough, National Inst. Of Mental Health, Covance/Otsuka, and Pfizer. Dr. Bangalore has received research support from Supernus. Dr. Hurt has received research support from Bristol-Myers Squibb. Dr. Findling has received research support, acted as a consultant and/or served on a speaker's bureau for Alexza Pharmaceuticals, American Psychiatric Press, AstraZeneca, Bracket, Bristol-Myers Squibb, Clinsys, Cognition Group, Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press, Johnson and Johnson, KemPharm, Eli Lilly and Co., Lundbeck, Merck, NIH, Novartis, Noven, Otsuka, Pfizer, Physicians Postgraduate Press, Rhodes Pharmaceuticals, Roche, Sage, Seaside Pharmaceuticals, Shire, Stanley Medical Research Institute, Sunovion, Supernus Pharmaceuticals, Transcept Pharmaceuticals, Validus, and WebMD. Ms. Kipp has received research support from Supernus. Ms. Baker has received research support from Amicus, BioMarin, Enobia, Genzyme, GlaxoSmithKline, Hyperion, Shire, Supernus, and Ultragenyx. Drs. Gadow, Molina, Li, Schneider, Butter, Sprafkin, Rice, and Farmer; and Ms. Austin, Ms. Buchan-Page, Ms. Arradaza, and Ms. Grondhuis report no biomedical financial interests or potential conflicts of interest. NIH Public Access Author Manuscript J Am Acad Child Adolesc Psychiatry. Author manuscript; available in PMC 2015 January 01. Published in final edited form as: J Am Acad Child Adolesc Psychiatry. 2014 January ; 53(1): 47–60.e1. doi:10.1016/j.jaac.2013.09.022. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript psychostimulant and parent training (PT) in behavior management for children with severe aggression Method—We randomized 168 children age 6–12 years (mean 8.89 ±2.01) with severe physical aggression to a 9-week trial of PT, stimulant, and placebo (Basic treatment; n=84) or PT, stimulant, and risperidone (Augmented treatment; n=84). All had diagnoses of attention-deficit/ hyperactivity disorder (ADHD) and either oppositional defiant (n= 124) or conduct disorder (n= 44). Children received psychostimulant (usually OROS methylphenidate) for 3 weeks, titrated for optimal effect, while parents received PT. If there was room for improvement at the end of Week 3, either placebo or risperidone was added. Assessments included parent ratings on the Nisonger Child Behavior Rating Form (NCBRF; Disruptive-Total subscale = Primary outcome) and Antisocial Behavior Scale (ABS); blinded clinicians rated change on the Clinical Global Impressions (CGI) scale. Results—Compared to Basic treatment (PT + stimulant[STIM][44.8±14.6 mg/day] + placebo [1.88±0.72]), Augmented treatment (PT + STIM[46.1±16.8 mg/day] + risperidone[1.65±0.75]) showed statistically significant improvement on the NCBRF Disruptive–Total subscale (treatmentby-time interaction p= 0.0016), the NCBRF Social Competence subscale (p= 0.0049), and ABS Reactive Aggression (p= 0.01). CGI scores were substantially improved for both groups but did not discriminate between treatments (CGI-I ≤ 2, 70% for Basic treatment vs. 79% for Augmented treatment). Prolactin elevations and gastrointestinal upset occurred more with Augmented; other adverse events differed modestly from Basic treatment; weight gain within the Augmented treatment group was minor. Conclusions—Risperidone provided moderate but variable improvement in aggressive and other seriously disruptive child behavior when added to PT and optimized stimulant treatment. Clinical trial registration information—Treatment of Severe Childhood Aggression (The TOSCA Study); http://clinicaltrials.gov/; NCT00796302.