What does risperidone add to parent training and stimulant for severe aggression in child attention-deficit/hyperactivity disorder?

Abstract

Objective: Although combination pharmacotherapy is common in child and adolescent psychiatry, there has been little research evaluating it. The value of adding risperidone to concurrent psychostimulant and parent training (PT) in behavior management for children with severe aggression was tested.

Method: One hundred sixty-eight children 6 to 12 years old (mean age 8.89 ± 2.01 years) with severe physical aggression were randomized to a 9-week trial of PT, stimulant (STIM), and placebo (Basic treatment; n = 84) or PT, STIM, and risperidone (Augmented treatment; n = 84). All had diagnoses of attention-deficit/hyperactivity disorder and oppositional-defiant disorder (n = 124) or conduct disorder (n = 44). Children received psychostimulant (usually Osmotic Release Oral System methylphenidate) for 3 weeks, titrated for optimal effect, while parents received PT. If there was room for improvement at the end of week 3, placebo or risperidone was added. Assessments included parent ratings on the Nisonger Child Behavior Rating Form (Disruptive-Total subscale was the primary outcome) and Antisocial Behavior Scale; blinded clinicians rated change on the Clinical Global Impressions scale.

Results: Compared with Basic treatment (PT + STIM [44.8 ± 14.6 mg/day] + placebo [1.88 mg/day ± 0.72]), Augmented treatment (PT + STIM [46.1 ± 16.8 mg/day] + risperidone [1.65 mg/day ± 0.75]) showed statistically significant improvement on the Nisonger Child Behavior Rating Form Disruptive-Total subscale (treatment-by-time interaction, p = .0016), the Nisonger Child Behavior Rating Form Social Competence subscale (p = .0049), and Antisocial Behavior Scale Reactive Aggression subscale (p = .01). Clinical Global Impressions scores were substantially improved for the 2 groups but did not discriminate between treatments (Clinical Global Impressions-Improvement score ≤2, 70% for Basic treatment versus 79% for Augmented treatment). Prolactin elevations and gastrointestinal upset occurred more with Augmented treatment; other adverse events differed modestly from Basic treatment; weight gain in the Augmented treatment group was minor.

Conclusions: Risperidone provided moderate but variable improvement in aggressive and other seriously disruptive child behaviors when added to PT and optimized stimulant treatment. Clinical trial registration information-Treatment of Severe Childhood Aggression (The TOSCA Study), URL: https://ichgcp.net/clinical-trials-registry/NCT00796302" title="See in ClinicalTrials.gov">NCT00796302.

Keywords: disruptive behavior disorders; parent training; physical aggression; psychostimulants; risperidone.

Conflict of interest statement

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.

Copyright © 2014 American Academy of Child and Adolescent Psychiatry. All rights reserved.

Figures

Figure 1

CONSORT diagram showing subject allocation and subject attrition. Note: All 168 subjects were retained in the mixed model analysis regardless of whether they exited the study before Week 9, failed to respond, or were clinical responders to Basic (parent training [PT] + stimulant [STIM]). a Although 2nd medication was dispensed, subject was lost to follow-up with no Week 4 assessments.

Figure 2

Nisonger Child Behavior Rating Form (NCBRF) Disruptive Behavior Total (D-Total) score as a function of treatment condition and study visit. Note: Mean doses for risperidone are provided above the X axis.