Effects of Risperidone and Parent Training on Adaptive Functioning in Children With Pervasive Developmental Disorders and Serious Behavioral Problems

doi:10.1016/j.jaac.2011.11.010

Journal of the American Academy of Child & Adolescent Psychiatry

Volume 51, Issue 2, February 2012, Pages 136-146

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https://doi.org/10.1016/j.jaac.2011.11.010 Get rights and content

Objective

Children with Pervasive Developmental Disorders (PDDs) have social interaction deficits, delayed communication, and repetitive behaviors as well as impairments in adaptive functioning. Many children actually show a decline in adaptive skills compared with age mates over time.

Method

This 24-week, three-site, controlled clinical trial randomized 124 children (4 through 13 years of age) with PDDs and serious behavioral problems to medication alone (MED; n = 49; risperidone 0.5 to 3.5 mg/day; if ineffective, switch to aripiprazole was permitted) or a combination of medication plus parent training (PT) (COMB; n = 75). Parents of children in COMB received an average of 11.4 PT sessions. Standard scores and Age-Equivalent scores on Vineland Adaptive Behavior Scales were the outcome measures of primary interest.

Results

Seventeen subjects did not have a post-randomization Vineland assessment. Thus, we used a mixed model with outcome conditioned on the baseline Vineland scores. Both groups showed improvement over the 24-week trial on all Vineland domains. Compared with MED, Vineland Socialization and Adaptive Composite Standard scores showed greater improvement in the COMB group (p = .01 and .05, and effect sizes = 0.35 and 0.22, respectively). On Age Equivalent scores, Socialization and Communication domains showed greater improvement in COMB versus MED (p = .03 and 0.05, and effect sizes = 0.33 and 0.14, respectively). Using logistic regression, children in the COMB group were twice as likely to make at least 6 months' gain (equal to the passage of time) in the Vineland Communication Age Equivalent score compared with MED (p = .02). After controlling for IQ, this difference was no longer significant.

Conclusion

Reduction of serious maladaptive behavior promotes improvement in adaptive behavior. Medication plus PT shows modest additional benefit over medication alone. Clinical trial registration information–RUPP PI PDD: Drug and Behavioral Therapy for Children With Pervasive Developmental Disorders; http://www.clinicaltrials.gov; NCT00080145.

Section snippets

Study Design

The study design has been described in detail in a previous publication.¹⁷ Briefly, 124 children were randomly assigned, in a 3:2 ratio, to MED (medication only, n = 49) or COMB (medication plus parent training, n = 75) for 6 months. The unbalanced randomization was intended to facilitate recruitment based on the assumption that families might prefer COMB treatment. The primary outcome measure was the parent-rated Home Situations Questionnaire on compliance in everyday life. Because a moderate

Results

A total of 199 subjects were screened across the three recruitment sites.¹² Of these, 124 subjects (105 boys and 19 girls) were randomly assigned to COMB (n = 75) or MED (n = 49). As per protocol, five subjects were withdrawn from the trial at week 8 because of lack of efficacy (these subjects had previous unsuccessful trials of aripiprazole). Over the course of the 24-week trial, an additional 24 subjects exited early (nine between baseline and week 8; six between weeks 12 and 15; and nine

Discussion

The study model predicted that, compared with medication alone, medication plus PT would promote greater reduction in noncompliant and disruptive behavior, leading to improved adaptive functioning over time. Thus, the proximal outcomes (maladaptive behavior that brought the subjects into the study) were conceptually linked to more distal outcomes (adaptive functioning). In a previous report we showed that COMB was superior to MED in reducing maladaptive behavior.¹² This report evaluated the

References (32)

M.G. Aman et al.
Medication and parent training in children with pervasive developmental disorders and serious behavioral problems: results from a randomized clinical trial
J Am Acad Child Adolesc Psychiatry
(2009)
S.K. Williams et al.
Risperidone and adaptive behavior in children with autism
J Am Acad Child Adolesc Psychiatry
(2006)
E.C. Brown et al.
Factor analysis and norms for parent ratings on the Aberrant Behavior Checklist—Community for young people in special education
Res Dev Disabil
(2002)
R.N. Marcus et al.
A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder
J Am Acad Child Adoles Psychiatry
(2009)
E. Fombonne
Epidemiology of pervasive developmental disorders
Pediatr Res
(2009)
M. King et al.
Diagnostic change and increased prevalence of autism
Int J Epidemiol
(2009)
D.L. Leslie et al.
Health care expenditures associated with autism spectrum disorders
Arch Pediatr Adolesc Med
(2007)
L. Lecavalier
Behavioral and emotional problems in young people with pervasive developmental disorders: relative prevalence, effects of subject characteristics, and empirical classification
J Autism Dev Disord
(2006)
K.D. Gadow et al.
Comparison of DSM-IV symptoms in elementary school-aged children with PDD versus clinic and community samples
Autism
(2005)
R.E. Rosenberg et al.
Psychotropic medication use among children with autism spectrum disorders enrolled in a national registry, 2007-2008
J Autism Dev Disord
(2010)

M.G. Aman et al.

Medication patterns in patients with autism: temporal, regional, and demographic influences

J Child Adolesc Psychopharmacol

(2005)

D.P. Oswald et al.

Medication use among children with autism spectrum disorders

J Child Adolesc Psychopharmacol

(2007)

G.P. Hanley et al.

Functional analysis of problem behavior: a review

J Appl Behav Anal

(2003)

Risperidone in children with autism and serious behavior problems

N Engl J Med

(2002)

Risperidone treatment of autistic disorder: longer term benefits and blinded discontinuation after six months

Am J Psychiatry

(2005)

A.S. Carter et al.

The Vineland Adaptive Behavior Scales: supplementary norms for individuals with autism

J Autism Dev Disord

(1998)

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: This article was reviewed under and accepted by Dr. John T. Walkup, M.D.

: This work was funded by the National Institute of Mental Health (NIMH) by the following Research Units on Pediatric Psychopharmacology (RUPP) grants: U10MH66764 (Yale); U10MH66766 (Indiana University); U10MH66768 (Ohio State University). NIMH staff participated in the design and implementation, analysis of data, and authorship of the manuscript. Johnson and Johnson Pharmaceutical Research and Development provided active risperidone for the study, but had no role in the design and implementation, analysis of the data, or authorship of the manuscript. This publication was also supported by the Yale Clinical and Translational Science Award (CTSA) UL1 RR024139, Indiana University CTSA UL1 RR025761, and Ohio State University CTSA UL1 RR025755 from the National Center for Research Resources (NCRR). Drs. Scahill, McDougle, Aman, Johnson, Handen, Bearss, Dziura, Butter, Swiezy, Arnold, Stigler, Sukhodolsky, Lecavalier, Mulick, Pozdol, Nikolov, Korzekwa, and Vitiello, and Ms. Ritz, Ms. Holloway, Ms. Gavaletz, Ms. Kohn, Ms. Koenig, Ms. Grinnon, and Ms. Yu received salary support from NIMH in support of the study.

: The opinions and assertions contained in this report are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Health and Human Services, the National Institutes of Health, or the National Institute of Mental Health. Drs. Dzuira and Scahill had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. National Institute of Mental Health staff participated in the study design and implementation, analysis of the data, and composition of the manuscript.

: This article is discussed in an editorial by Dr. Thomas W. Frazier on page 129.

: Disclosure: Dr. Scahill serves as a consultant for BioMarin, Boehringer-Ingelheim, Hoffman, NeuroSearch, and Pfizer. He has received research support from Shire and Seaside. Dr. Aman has served as a consultant to Bristol-Myers Squibb, BioMarin, Forest, Hoffman, Pfizer, and Supernus. He has received research support from Bristol-Myers Squibb and Johnson and Johnson. Dr. Arnold has served as a consultant to Abbott, BioMarin, Novartis, Noven, Organon, Shire, and Targacept. He has received research support from Eli Lilly and Co., Autism Speaks, Neuropharm, the National Institute of Mental Health (NIMH), Shire, and Targacept. Dr. McDougle has served as a consultant to Bristol-Myers Squibb and Forest. He has received research support from and served on the speakers' bureau for Bristol-Myers Squibb. Dr. Stigler has received research support from Bristol-Myers Squibb, Eli Lilly and Co., and Janssen. Dr. Handen has received research support from Bristol-Myers Squibb, Neuropharm, and Pediamed. He has served as a consultant to Forest and Eisai. Drs. Bearss, Sukhodolsky, Nikolov, Dziura, Butter, Lecavalier, Mulick, Swiezy, Johnson, and Vitiello, and Ms. Koenig, Ms. Gavaletz, Ms. Yu, Ms. Holloway, Ms. Kohn, Ms. Pozdol, Ms. Korzekwa, and Ms. Grinnon report no biomedical financial interests or potential conflicts of interest.

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New researchEffects of Risperidone and Parent Training on Adaptive Functioning in Children With Pervasive Developmental Disorders and Serious Behavioral Problems

Objective

Method

Results

Conclusion

Section snippets

Study Design

Results

Discussion

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

Res Dev Disabil

J Am Acad Child Adoles Psychiatry

Epidemiology of pervasive developmental disorders

Pediatr Res

Diagnostic change and increased prevalence of autism

Int J Epidemiol

Health care expenditures associated with autism spectrum disorders

Arch Pediatr Adolesc Med

Behavioral and emotional problems in young people with pervasive developmental disorders: relative prevalence, effects of subject characteristics, and empirical classification

J Autism Dev Disord

Comparison of DSM-IV symptoms in elementary school-aged children with PDD versus clinic and community samples

Autism

Psychotropic medication use among children with autism spectrum disorders enrolled in a national registry, 2007-2008

J Autism Dev Disord

Medication patterns in patients with autism: temporal, regional, and demographic influences

J Child Adolesc Psychopharmacol

Medication use among children with autism spectrum disorders

J Child Adolesc Psychopharmacol

Functional analysis of problem behavior: a review

J Appl Behav Anal

Risperidone in children with autism and serious behavior problems

N Engl J Med

Risperidone treatment of autistic disorder: longer term benefits and blinded discontinuation after six months

Am J Psychiatry

The Vineland Adaptive Behavior Scales: supplementary norms for individuals with autism

J Autism Dev Disord

New research
Effects of Risperidone and Parent Training on Adaptive Functioning in Children With Pervasive Developmental Disorders and Serious Behavioral Problems