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Evidence-Based Integrated Treatment in Autism Spectrum Disorders
EDITORIAL
Evidence-Based Integrated Treatment in Autism Spectrum Disorders Joel D. Bregman,
T
he study by Arnold et al.1 in this issue of the Journal addresses a topic of significant importance to child and adolescent psychiatrists— the implementation of treatment plans that result in sustained improvement in behavioral and social functioning of those with autism spectrum disorders (ASDs). It is likely that this can best be achieved by identifying treatment packages that combine individual interventions that are compatible and act synergistically. The present study examined whether the short-term (24-week) clinical benefits derived from combining psychopharmacologic treatment (risperidone) with parent behavioral training are sustained at 1-year post-treatment follow-up. The investigators previously demonstrated that combined treatment (COMB) was significantly more efficacious than medication only (MED) in decreasing noncompliance and some serious problem behaviors (at lower medication dosages) after 24 weeks of treatment.2 This differential treatment advantage dissipated at 1-year follow-up and was no longer statistically significant. However, methodologic limitations likely contributed to this finding (including a loss of power owing to subject attrition and retention of a subgroup that was less responsive to parent behavioral training at the 24-week study endpoint). The increasing prevalence of ASDs and the increased recognition of their significant clinical heterogeneity have fueled interest in identifying effective, evidence-based treatment approaches that address core impairments and commonly cooccurring conditions. Although there have been numerous studies of the short-term treatment efficacy in ASDs (see comprehensive, systematic reviews3-7), there have been relatively few replications of specific interventions and limited integration of approaches in an effort to address the wide range of needs experienced by those with ASDs. Fortunately, there has been increasing recognition of the commonalities and compatibility of various approaches and
M.D.
openness to the potential value and synergy of integrating different interventions. Although treatments are often combined in clinical practice, few studies have examined the efficacy of integrated treatments. The significant majority of studies have evaluated short- rather than longterm effects. There also have been few studies evaluating the potential efficacy of interventions administered by parents, teachers, and other significant individuals in the lives of those with ASDs after systematic training by experts (in an effort to increase treatment access, generalization, and cost-effectiveness). It is also of note that the reviews of psychopharmacologic treatment have identified only three medications that meet research criteria as evidenced based (i.e., risperidone, aripiprazole, and methylphenidate),8 stressing the need for future studies. Important considerations in the search for effective treatments include the differential efficacy of specific interventions across individuals with ASD, the goal of increasing the generalization and long-term maintenance of skills and therapeutically enhanced prosocial behavior, and the need for interventions that can be implemented by families, educators, and community support personnel. Individualization, practicality, and costeffectiveness have become key components in the development of successful treatment approaches. In view of the complex interplay of impairments across several developmental domains and the heterogeneity inherent in ASDs, it is most important that combined interventions be identified and based on genetic, phenotypic, and environmental factors that predict/moderate treatment responsiveness.9 The present study is unique in assessing the potential sustained benefit of combining psychopharmacologic and behavioral treatments that target serious problem behavior (e.g., aggression, self-injury, outbursts, environmental
JOURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY VOLUME 51 NUMBER 11 NOVEMBER 2012
www.jaacap.org
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BREGMAN
destruction, marked noncompliance) in ASDs as assessed by the Home Situations Questionnaire and the Aberrant Behavior Checklist.2 Of the 124 families in the original study, 87 (70%) participated in the follow-up study, completing the Home Situations Questionnaire, Aberrant Behavior Checklist, and a brief report measure that ascertained interim treatment modalities received by the subjects and the continued use or seeking of parent behavioral techniques (among the families in the COMB and MED-only groups, respectively). The investigators found that the impressive clinical advantage experienced by the COMB group decreased appreciably at 1-year follow-up. However, a portion of this narrowing of differential efficacy was likely owing to a loss of power related to the smaller sample size and “biased attrition” (participants lost to follow-up contributed significantly to differential efficacy at the 24-week study endpoint and included a disproportionate percentage of subjects with Asperger syndrome and pervasive developmental disorder not otherwise specified in addition to risperidone nonresponders). The parent training intervention may have resulted in benefits in domains other than decreased noncompliance and serious problem behavior, such as improved adaptive skills, socialization, and community participation and integration. Such a broader efficacy may have contributed to the very large percentage of families in the COMB group continuing to implement (and seek additional) parent training. In addition, the decreased differential efficacy may have resulted from higher expectations by parents with increased skills and confidence in promoting responsible pro-social behavior in their children. For treatment individualization to be successful, predictors of responsiveness to specific interventions need to be identified. With this knowledge and a thorough assessment (i.e., developmental, medical, and family histories, full phenotypic characterization, and a functional behavior assessment), an intervention package with a high chance
of success could be developed. In a predictor/ mediator analysis, the investigators of this study explored the possibility that gains in adaptive skills (assessed by the Vineland Adaptive Behavior Scales) from baseline to the 24-week study endpoint correlate with changes in noncompliance and serious problem behavior from 24 weeks to follow-up. For the COMB group, an improvement in adaptive behavior during the main study correlated with an improved compliance at study follow-up. The inverse was true for the MED-alone group. Advances in skill development may promote responsiveness to behavioral strategies, including differential reinforcement, targeting cooperative behavior in general. Future studies should develop algorithms for selecting combined interventions (psychopharmacologic, behavioral, social-communicative, and ecologic) based on predictor/mediator analyses and include a range of follow-up measurements (e.g., externalizing and internalizing symptomatology, adaptive skills, academic achievement, family participation, community integration, and skill generalization). It would also be valuable to study the benefits of decreasing affective and behavioral symptoms (e.g., anxiety, dysphoria, deficits in executive functions) on the effectiveness of interventions promoting skill development in core (socialization, social communication, flexibility of thought and behavior) and comorbid domains. & Accepted August 28, 2012. Dr. Bregman is with the Center for Autism, Philadelphia, PA. Disclosure: Dr. Bregman has served as a consultant to Pfizer Pharmaceuticals. He has participated in a multisite clinical trial sponsored by Forest Laboratories. Correspondence to Joel D. Bregman, M.D., Medical Director, Director of Psychiatry, The Center for Autism, 3905 Ford Road, Suite 5, Philadelphia, PA 19131; e-mail: JBregman@ thecenterforautism.org 0890-8567/$36.00/©2012 American Academy of Child and Adolescent Psychiatry http://dx.doi.org/10.1016/j.jaac.2012.08.022
REFERENCES 1. Arnold LE, Aman MG, Li X, et al. Research Units of Pediatric Psychopharmacology (RUPP) autism network randomi zed clinical trial of parent training and medication: one year follow-up. J Am Acad Child Adolesc Psychiatry. 2012;51:11731184. 2. Aman MG, McDougle CJ, Scahill L, et al. Medication and parent training in children with pervasive developmental disorders and serious behavior problems: results from a randomized clinical trial [erratum appears in J Am Acad Child Adolesc
Psychiatry. 2010;49:727]. J Am Acad Child Adolesc Psychiatry. 2009;48:1143-1154. 3. Odom SL, Boyd BA, Hall LJ, Hume K. Evaluation of comprehensive treatment models for individuals with autism spectrum disorders [erratum appears in J Autism Dev Disord. 2010;40:437]. J Autism Dev Disord. 2010;40:425-436. 4. Odom SL, Collet-Klingenberg L, Rogers SJ, Hatton DD. Evidencebased practices in interventions for children and youth with ASD. Prev School Fail. 2010;54:275-282.
JOURNAL 1114
www.jaacap.org
OF THE
AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY VOLUME 51 NUMBER 11 NOVEMBER 2012
EDITORIAL
5. NSP. National Standards Report: The National Standards Project— Addressing the Need for Evidence-Based Practice Guidelines for Autism Spectrum Disorders. Randolph, MA: The National Autism Center; 2009. 6. Young J, Corea C, Kimani J, Mandell D. Autism Spectrum Disorders (ASDs) Services: Final Report on Environmental Scan. Columbia, MD: IMPAQ International, LLC; 2010:159. 7. Warren Z, Veenstra-VanderWeele J, Stone W, et al. Therapies for children with autism spectrum disorders. Comp Effect Rev. Rockville, MD: Agency for Healthcare Research and Quality (US); 2011;26.
8. Huffman LC, Sutcliffe TL, Tanner IS, Feldman HM. Management of symptoms in children with autism spectrum disorders: a comprehensive review of pharmacologic and complementaryalternative medicine treatments. J Dev Behav Pediatr. 2011;32: 56-68. 9. Schreibman L, Dufek S, Cunningham AB. Identifying Moderators of Treatment Outcome for Children with Autism. International Handbook of Autism and Pervasive Developmental Disorders. New York: Springer Science ⫹ Business Media; 2011: 295-305.
JOURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY VOLUME 51 NUMBER 11 NOVEMBER 2012
www.jaacap.org
1115
Evidence-Based Integrated Treatment in Autism Spectrum Disorders Joel D. Bregman,
T
he study by Arnold et al.1 in this issue of the Journal addresses a topic of significant importance to child and adolescent psychiatrists— the implementation of treatment plans that result in sustained improvement in behavioral and social functioning of those with autism spectrum disorders (ASDs). It is likely that this can best be achieved by identifying treatment packages that combine individual interventions that are compatible and act synergistically. The present study examined whether the short-term (24-week) clinical benefits derived from combining psychopharmacologic treatment (risperidone) with parent behavioral training are sustained at 1-year post-treatment follow-up. The investigators previously demonstrated that combined treatment (COMB) was significantly more efficacious than medication only (MED) in decreasing noncompliance and some serious problem behaviors (at lower medication dosages) after 24 weeks of treatment.2 This differential treatment advantage dissipated at 1-year follow-up and was no longer statistically significant. However, methodologic limitations likely contributed to this finding (including a loss of power owing to subject attrition and retention of a subgroup that was less responsive to parent behavioral training at the 24-week study endpoint). The increasing prevalence of ASDs and the increased recognition of their significant clinical heterogeneity have fueled interest in identifying effective, evidence-based treatment approaches that address core impairments and commonly cooccurring conditions. Although there have been numerous studies of the short-term treatment efficacy in ASDs (see comprehensive, systematic reviews3-7), there have been relatively few replications of specific interventions and limited integration of approaches in an effort to address the wide range of needs experienced by those with ASDs. Fortunately, there has been increasing recognition of the commonalities and compatibility of various approaches and
M.D.
openness to the potential value and synergy of integrating different interventions. Although treatments are often combined in clinical practice, few studies have examined the efficacy of integrated treatments. The significant majority of studies have evaluated short- rather than longterm effects. There also have been few studies evaluating the potential efficacy of interventions administered by parents, teachers, and other significant individuals in the lives of those with ASDs after systematic training by experts (in an effort to increase treatment access, generalization, and cost-effectiveness). It is also of note that the reviews of psychopharmacologic treatment have identified only three medications that meet research criteria as evidenced based (i.e., risperidone, aripiprazole, and methylphenidate),8 stressing the need for future studies. Important considerations in the search for effective treatments include the differential efficacy of specific interventions across individuals with ASD, the goal of increasing the generalization and long-term maintenance of skills and therapeutically enhanced prosocial behavior, and the need for interventions that can be implemented by families, educators, and community support personnel. Individualization, practicality, and costeffectiveness have become key components in the development of successful treatment approaches. In view of the complex interplay of impairments across several developmental domains and the heterogeneity inherent in ASDs, it is most important that combined interventions be identified and based on genetic, phenotypic, and environmental factors that predict/moderate treatment responsiveness.9 The present study is unique in assessing the potential sustained benefit of combining psychopharmacologic and behavioral treatments that target serious problem behavior (e.g., aggression, self-injury, outbursts, environmental
JOURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY VOLUME 51 NUMBER 11 NOVEMBER 2012
www.jaacap.org
1113
BREGMAN
destruction, marked noncompliance) in ASDs as assessed by the Home Situations Questionnaire and the Aberrant Behavior Checklist.2 Of the 124 families in the original study, 87 (70%) participated in the follow-up study, completing the Home Situations Questionnaire, Aberrant Behavior Checklist, and a brief report measure that ascertained interim treatment modalities received by the subjects and the continued use or seeking of parent behavioral techniques (among the families in the COMB and MED-only groups, respectively). The investigators found that the impressive clinical advantage experienced by the COMB group decreased appreciably at 1-year follow-up. However, a portion of this narrowing of differential efficacy was likely owing to a loss of power related to the smaller sample size and “biased attrition” (participants lost to follow-up contributed significantly to differential efficacy at the 24-week study endpoint and included a disproportionate percentage of subjects with Asperger syndrome and pervasive developmental disorder not otherwise specified in addition to risperidone nonresponders). The parent training intervention may have resulted in benefits in domains other than decreased noncompliance and serious problem behavior, such as improved adaptive skills, socialization, and community participation and integration. Such a broader efficacy may have contributed to the very large percentage of families in the COMB group continuing to implement (and seek additional) parent training. In addition, the decreased differential efficacy may have resulted from higher expectations by parents with increased skills and confidence in promoting responsible pro-social behavior in their children. For treatment individualization to be successful, predictors of responsiveness to specific interventions need to be identified. With this knowledge and a thorough assessment (i.e., developmental, medical, and family histories, full phenotypic characterization, and a functional behavior assessment), an intervention package with a high chance
of success could be developed. In a predictor/ mediator analysis, the investigators of this study explored the possibility that gains in adaptive skills (assessed by the Vineland Adaptive Behavior Scales) from baseline to the 24-week study endpoint correlate with changes in noncompliance and serious problem behavior from 24 weeks to follow-up. For the COMB group, an improvement in adaptive behavior during the main study correlated with an improved compliance at study follow-up. The inverse was true for the MED-alone group. Advances in skill development may promote responsiveness to behavioral strategies, including differential reinforcement, targeting cooperative behavior in general. Future studies should develop algorithms for selecting combined interventions (psychopharmacologic, behavioral, social-communicative, and ecologic) based on predictor/mediator analyses and include a range of follow-up measurements (e.g., externalizing and internalizing symptomatology, adaptive skills, academic achievement, family participation, community integration, and skill generalization). It would also be valuable to study the benefits of decreasing affective and behavioral symptoms (e.g., anxiety, dysphoria, deficits in executive functions) on the effectiveness of interventions promoting skill development in core (socialization, social communication, flexibility of thought and behavior) and comorbid domains. & Accepted August 28, 2012. Dr. Bregman is with the Center for Autism, Philadelphia, PA. Disclosure: Dr. Bregman has served as a consultant to Pfizer Pharmaceuticals. He has participated in a multisite clinical trial sponsored by Forest Laboratories. Correspondence to Joel D. Bregman, M.D., Medical Director, Director of Psychiatry, The Center for Autism, 3905 Ford Road, Suite 5, Philadelphia, PA 19131; e-mail: JBregman@ thecenterforautism.org 0890-8567/$36.00/©2012 American Academy of Child and Adolescent Psychiatry http://dx.doi.org/10.1016/j.jaac.2012.08.022
REFERENCES 1. Arnold LE, Aman MG, Li X, et al. Research Units of Pediatric Psychopharmacology (RUPP) autism network randomi zed clinical trial of parent training and medication: one year follow-up. J Am Acad Child Adolesc Psychiatry. 2012;51:11731184. 2. Aman MG, McDougle CJ, Scahill L, et al. Medication and parent training in children with pervasive developmental disorders and serious behavior problems: results from a randomized clinical trial [erratum appears in J Am Acad Child Adolesc
Psychiatry. 2010;49:727]. J Am Acad Child Adolesc Psychiatry. 2009;48:1143-1154. 3. Odom SL, Boyd BA, Hall LJ, Hume K. Evaluation of comprehensive treatment models for individuals with autism spectrum disorders [erratum appears in J Autism Dev Disord. 2010;40:437]. J Autism Dev Disord. 2010;40:425-436. 4. Odom SL, Collet-Klingenberg L, Rogers SJ, Hatton DD. Evidencebased practices in interventions for children and youth with ASD. Prev School Fail. 2010;54:275-282.
JOURNAL 1114
www.jaacap.org
OF THE
AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY VOLUME 51 NUMBER 11 NOVEMBER 2012
EDITORIAL
5. NSP. National Standards Report: The National Standards Project— Addressing the Need for Evidence-Based Practice Guidelines for Autism Spectrum Disorders. Randolph, MA: The National Autism Center; 2009. 6. Young J, Corea C, Kimani J, Mandell D. Autism Spectrum Disorders (ASDs) Services: Final Report on Environmental Scan. Columbia, MD: IMPAQ International, LLC; 2010:159. 7. Warren Z, Veenstra-VanderWeele J, Stone W, et al. Therapies for children with autism spectrum disorders. Comp Effect Rev. Rockville, MD: Agency for Healthcare Research and Quality (US); 2011;26.
8. Huffman LC, Sutcliffe TL, Tanner IS, Feldman HM. Management of symptoms in children with autism spectrum disorders: a comprehensive review of pharmacologic and complementaryalternative medicine treatments. J Dev Behav Pediatr. 2011;32: 56-68. 9. Schreibman L, Dufek S, Cunningham AB. Identifying Moderators of Treatment Outcome for Children with Autism. International Handbook of Autism and Pervasive Developmental Disorders. New York: Springer Science ⫹ Business Media; 2011: 295-305.
JOURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY VOLUME 51 NUMBER 11 NOVEMBER 2012
www.jaacap.org
1115