Therapies for Children With Autism Spectrum Disorders

908 Pages·2011·5.73 MB·English

Comparative  Effectiveness  Review
Number  26
Therapies  for  Children
With  Autism  Spectrum
Disorders
Comparative Effectiveness Review

Number 26

Therapies for Children With Autism Spectrum
Disorders

Prepared for:
Agency for Healthcare Research and Quality
U.S. Department of Health and Human Services
540 Gaither Road
Rockville, MD 20850
www.ahrq.gov

Contract No. 290-2007-10065-I

Prepared by:
Vanderbilt Evidence-based Practice Center
Nashville, TN

Investigators:
Zachary Warren, Ph.D.
Jeremy Veenstra-VanderWeele, M.D.
Wendy Stone, Ph.D.
Jennifer L. Bruzek, Ph.D.
Allison S. Nahmias, M.Ed.
Jennifer H. Foss-Feig, M.A.
Rebecca N. Jerome, M.L.I.S., M.P.H.
Shanthi Krishnaswami, M.B.B.S., M.P.H.
Nila A. Sathe, M.A., M.L.I.S.
Allison M. Glasser, B.A.
Tanya Surawicz, M.P.H.
Melissa L. McPheeters, Ph.D., M.P.H.

AHRQ Publication No. 11-EHC029-EF
April 2011
This report is based on research conducted by the Vanderbilt Evidence-based Practice Center
(EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville,
MD (Contract No. 290-2007-10065-I). The findings and conclusions in this document are those
of the author(s), who are responsible for its contents; the findings and conclusions do not
necessarily represent the views of AHRQ. Therefore, no statement in this report should be
construed as an official position of AHRQ or of the U.S. Department of Health and Human
Services.

The information in this report is intended to help health care decisionmakers—patients and
clinicians, health system leaders, and policymakers, among others—make well-informed
decisions and thereby improve the quality of health care services. This report is not intended to
be a substitute for clinical judgment. Anyone who makes decisions concerning the provision of
clinical care should consider this report in the same way as any medical reference and in
conjunction with all other pertinent information, i.e., in the context of available resources and
circumstances presented by individual patients.

This report may be used, in whole or in part, as the basis for development of clinical practice
guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage
policies. AHRQ or U.S. Department of Health and Human Services endorsement of such
derivative products may not be stated or implied.

This document is in the public domain and may be used and reprinted without permission except
those copyrighted materials noted for which further reproduction is prohibited without the
specific permission of copyright holders.

None of the investigators have any affiliations or financial involvement that conflicts with the
material presented in this report.

Suggested citation: Warren Z, Veenstra-VanderWeele J, Stone W, Bruzek JL, Nahmias AS,
Foss-Feig JH, Jerome RN, Krishnaswami S, Sathe NA, Glasser AM, Surawicz T, McPheeters
ML. Therapies for Children With Autism Spectrum Disorders. Comparative Effectiveness
Review No. 26. (Prepared by the Vanderbilt Evidence-based Practice Center under Contract No.
290-2007-10065-I.) AHRQ Publication No. 11-EHC029-EF. Rockville, MD: Agency for
Healthcare Research and Quality. April 2011. Available at:
www.effectivehealthcare.ahrq.gov/reports/final.cfm.

ii
Preface
The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health Care
Program as part of its mission to organize knowledge and make it available to inform decisions
about health care. As part of the Medicare Prescription Drug, Improvement, and Modernization
Act of 2003, Congress directed AHRQ to conduct and support research on the comparative
outcomes, clinical effectiveness, and appropriateness of pharmaceuticals, devices, and health
care services to meet the needs of Medicare, Medicaid, and the Children’s Health Insurance
Program (CHIP).

AHRQ has an established network of Evidence-based Practice Centers (EPCs) that produce
Evidence Reports/Technology Assessments to assist public- and private-sector organizations in
their efforts to improve the quality of health care. The EPCs now lend their expertise to the
Effective Health Care Program by conducting Comparative Effectiveness Reviews (CERs) of
medications, devices, and other relevant interventions, including strategies for how these items
and services can best be organized, managed, and delivered.

Systematic reviews are the building blocks underlying evidence-based practice; they focus
attention on the strengths and limits of evidence from research studies about the effectiveness
and safety of a clinical intervention. In the context of developing recommendations for practice,
systematic reviews are useful because they define the strengths and limits of the evidence,
clarifying whether assertions about the value of the intervention are based on strong evidence
from clinical studies. For more information about systematic reviews, see
http://effectivehealthcare.ahrq.gov/reference/purpose.cfm.

AHRQ expects that CERs will be helpful to health plans, providers, purchasers, government
programs, and the health care system as a whole. In addition, AHRQ is committed to presenting
information in different formats so that consumers who make decisions about their own and their
family’s health can benefit from the evidence.

Transparency and stakeholder input are essential to the Effective Health Care Program. Please
visit the Web site (www.effectivehealthcare.ahrq.gov) to see draft research questions and reports
or to join an e-mail list to learn about new program products and opportunities for input.
Comparative Effectiveness Reviews will be updated regularly.

Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H.
Director Director, Center for Outcomes and Evidence
Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality

Stephanie Chang, M.D., M.P.H. CAPT. Karen L. Siegel, P.T., M.A.
Director Task Order Officer
Evidence-based Practice Center Program Center for Outcomes and Evidence
Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality

iii
Acknowledgments
We are indebted to a tireless group of colleagues who made this report possible. Each step of
systematic reviews draws on the skills and attention of an entire team.
Ms. Rachel Bazan and Mr. Michael Tranchina were our energetic student workers. They
spent hours helping to track and file documents, and were always positive and always ready to
ensure that the project investigators had what they needed to do their work.
Ms. Ellen Davis and Ms. Cheena Clermont provided invaluable research assistance on this
report. Ms. Kathy Lee and Mr. Jeff Seroogy checked tables, formatted tables, and located
citations.
Dr. Mark Hartmann brought his extraordinary attention to detail—and his commitment to
perfection—to completion of the evidence tables. He spent many, many hours checking and
rechecking tables both for formatting and for content. His ability to point out inconsistencies and
enhance uniformity was key to ensuring smooth development of the evidence tables.
Ms. Nikki McKoy provided invaluable advice and assistance with formatting and logistics.
Ms. Rachel Walden and Ms. Pauline Alexander are key members of the library science staff.
Their support of Ms. Jerome, including their detailed approach to literature searching and data
abstraction, was invaluable. Their thoughtful attention to detail in reviewing abstracts and
articles for inclusion in the review was a generous gift to the project and to the EPC as a whole.
Technical Expert Panel
Robin Dea, M.D.
Regional Director, Autism Spectrum Disorder Services
Kaiser Permanente
Redwood City, CA

Bryan King, M.D.
Professor, Psychiatry and Behavioral Sciences
University of Washington
Seattle, WA

Susan Levy, M.D.
Medical Director, Regional Autism Center
The Children’s Hospital of Philadelphia
Philadelphia, PA

Catherine Lord, Ph.D.
Director, Autism and Communication Disorders Center
University of MichiganAnn Arbor, MI

Doris Lotz, M.D., M.P.H.
Medicaid Medical Director
New Hampshire Department of Health and Human Services

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Gary Mesibov, Ph.D.
Professor and Director, Division of TEACCH
UNC School of Medicine
Chapel Hill, NC

Tristram Smith, Ph.D.
Associate Professor, Department of Pediatrics
University of Rochester Medical Center
Rochester, NY

Paul Yoder, Ph.D.
Professor, Special Education
Vanderbilt Kennedy Center
Nashville, TN
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Therapies for Children With Autism Spectrum
Disorders
Structured Abstract
Objectives. The Vanderbilt Evidence-based Practice Center systematically reviewed evidence on
therapies for children ages 2 to 12 with autism spectrum disorders (ASDs). We focused on
treatment outcomes, modifiers of treatment effectiveness, evidence for generalization of
outcomes to other contexts, and evidence to support treatment decisions in children ages 0-2 at
risk for an ASD diagnosis.

Data. We searched MEDLINE,® ERIC, and PsycInfo.®

Review Methods. We included studies published in English from January 2000 to May 2010.
We excluded medical studies with fewer than 30 participants; behavioral, educational, and allied
health studies with fewer than 10 participants; and studies lacking relevance to treatment for
ASDs.

Results. Of 159 unique studies included, 13 were good quality, 56 were fair, and 90 poor. The
antipsychotic drugs risperidone and aripiprazole demonstrate improvement in challenging
behavior that includes emotional distress, aggression, hyperactivity, and self-injury, but both
have high incidence of harms. No current medical interventions demonstrate clear benefit for
social or communication symptoms in ASDs. Evidence supports early intensive behavioral and
developmental intervention, including the University of California, Los Angeles (UCLA)/Lovaas
model and Early Start Denver Model (ESDM) for improving cognitive performance, language
skills, and adaptive behavior in some groups of children. Data are preliminary but promising for
intensive intervention in children under age 2. All of these studies need to be replicated, and
specific focus is needed to characterize which children are most likely to benefit. Evidence
suggests that interventions focusing on providing parent training and cognitive behavioral
therapy (CBT) for bolstering social skills and managing challenging behaviors may be useful for
children with ASDs to improve social communication, language use, and potentially, symptom
severity. The Treatment and Education of Autistic and Communication related handicapped
CHildren (TEACCH) program demonstrated some improvements in motor skills and cognitive
measures. Little evidence is available to assess other behavioral interventions, allied health
therapies, or complementary and alternative medicine. Information is lacking on modifiers of
effectiveness, generalization of effects outside the treatment context, components of
multicomponent therapies that drive effectiveness, and predictors of treatment success.

Conclusions. Medical interventions including risperidone and aripiprazole show benefit for
reducing challenging behaviors in some children with ASDs, but side effects are significant.
Some behavioral and educational interventions that vary widely in terms of scope, target, and
intensity have demonstrated effects, but the lack of consistent data limits our understanding of
whether these interventions are linked to specific clinically meaningful changes in functioning.
The needs for continuing improvements in methodologic rigor in the field and for larger multisite
studies of existing interventions are substantial. Better characterization of children in these
studies to target treatment plans is imperative.
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Contents
Executive Summary ...................................................................................................................ES-1
Introduction ......................................................................................................................................1
Need for Evidence for Treatment of Autism Spectrum Disorders in Children ........................1
Behavioral Interventions ......................................................................................................4
Educational Interventions ....................................................................................................5
Medical and Related Interventions ......................................................................................6
Allied Health Interventions ..................................................................................................9
Complementary and Alternative Medicine (CAM) Interventions .....................................11
Importance of This Review ................................................................................................12
Scope of This Evidence Report..........................................................................................12
Key Questions and Analytic Framework ...............................................................................13
Key Questions ....................................................................................................................13
Analytic Framework for Therapies for Children With ASDs ............................................14
Organization of This Evidence Report ..............................................................................14
Technical Expert Panel (TEP) ...........................................................................................15
Uses of This Report ...........................................................................................................15
Methods..........................................................................................................................................17
Literature Review Methods ....................................................................................................17
Inclusion and Exclusion Criteria ........................................................................................17
Literature Search and Retrieval Process ............................................................................19
Categorization of Interventions..........................................................................................19
Literature Synthesis ................................................................................................................21
Development of Evidence Table and Data Abstraction Process .......................................21
Assessing Methodological Quality of Individual Studies ..................................................22
Strength of Available Evidence .........................................................................................27
Results ............................................................................................................................................28
Article Selection .....................................................................................................................28
KQ1. Effects of Treatment on Core and Commonly Associated Symptoms in Children
With ASDs: Behavioral Interventions ...................................................................................29
Early Intensive Behavioral and Developmental Interventions ..........................................30
Social Skills Interventions .................................................................................................37
Play-/Interaction-Based Interventions ...............................................................................42
Behavioral Interventions Focused on Associated Behaviors .............................................45
Other Behavioral Interventions ..........................................................................................50
KQ1. Effects of Treatment on Core and Commonly Associated Symptoms in Children
With ASDs: Educational Interventions .................................................................................52
TEACCH............................................................................................................................53
Broad-Based Educational Approaches ..............................................................................55
Computer-Based Educational Approaches ........................................................................57
KQ1. Effects of Treatment on Core and Commonly Associated Symptoms in Children
With ASDs: Medical Interventions .......................................................................................59
Antipsychotics....................................................................................................................60
Serotonin Reuptake Inhibitors ...........................................................................................67
Stimulants and Other Medications To Treat Hyperactivity ...............................................70
Secretin ..............................................................................................................................72
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Dietary and Other Medical Interventions ..........................................................................73
KQ1. Effects of Treatment on Core and Commonly Associated Symptoms in Children
With ASDs: Allied Health Interventions ................................................................................77
Language Interventions ......................................................................................................78
Sensory- and Auditory-Focused Interventions ..................................................................80
Additional Allied Health Interventions ..............................................................................83
KQ1. Effects of Treatment on Core and Commonly Associated Symptoms in Children
With ASDs: Complementary and Alternative Medicine (CAM) Interventions ....................84
CAM Interventions ............................................................................................................84
KQ2. Modifiers of Treatment Outcomes ................................................................................87
Behavioral Interventions ....................................................................................................88
Educational Interventions ..................................................................................................91
Medical Interventions ........................................................................................................91
CAM Interventions ............................................................................................................93
KQ3. Early Results in the Treatment Phase That Predict Outcomes .....................................93
Early Identifiable Changes Predicting Response/Outcome ...............................................93
KQ4. End of Treatment Effects That Predict Outcomes ........................................................93
KQ5. Generalization of Treatment Effects .............................................................................94
KQ6. Drivers of Treatment Effects ........................................................................................95
KQ7. Treatment Approaches in Children Under Age Two at Risk for Diagnosis
of ASDs ..................................................................................................................................95
Discussion ......................................................................................................................................98
Outcomes and Strength of Evidence of Therapies .................................................................99
Effectiveness of Behavioral Interventions .........................................................................99
Effectiveness of Educational Interventions .....................................................................106
Effectiveness of Medical and Related Interventions .......................................................107
Effectiveness of Allied Health Interventions ...................................................................110
Effectiveness of CAM Interventions ...............................................................................112
Assessment of Domains for Strength of Evidence ..........................................................112
KQ2. Modifiers of Treatment Outcomes .............................................................................115
KQ3. Early Results in the Treatment Phase That Predict Outcomes ...................................117
KQ4. End of Treatment Effects That Predict Outcomes ......................................................117
KQ5. Generalization of Treatment Effects ...........................................................................118
KQ6. Drivers of Treatment Effects ......................................................................................118
KQ7. Treatment Approaches in Children Under Age Two at Risk for ASDs .....................118
Quality Considerations .........................................................................................................118
Applicability .........................................................................................................................119
Review of Systematic Reviews ............................................................................................120
Future Research ....................................................................................................................121
State of the Literature.......................................................................................................121
Gaps in Areas of Research ...............................................................................................122
Methodologic Issues ........................................................................................................124
Conclusions ..........................................................................................................................125
References ....................................................................................................................................128
Acronyms/Abbreviations .............................................................................................................145
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Tables
Table A. Description of interventions ........................................................................................ES-2
Table 1. Description of behavioral interventions addressed in the report .......................................4
Table 2. Description of educational interventions addressed in the report ......................................6
Table 3. Description of medical and related interventions addressed in the report .........................8
Table 4. Description of allied health interventions addressed in the report ...................................11
Table 5. Description of CAM interventions addressed in the report .............................................12
Table 6. Inclusion and exclusion criteria .......................................................................................17
Table 7. Overview of diagnostic tools used in quality scoring hierarchy ......................................23
Table 8. Quality scoring algorithm ...............................................................................................26
Table 9. Overview of behavioral studies ......................................................................................30
Table 10. Outcomes of early intensive behavioral and developmental interventions ..................35
Table 11. Outcomes of RCTs of social skills behavioral interventions ........................................41
Table 12. Outcomes of RCTs assessing play-/interaction-based interventions .............................45
Table 13. Studies assessing interventions targeting conditions commonly associated
with ASDs ......................................................................................................................................47
Table 14. Overview of educational studies ....................................................................................53
Table 15. Outcomes of studies assessing educational interventions .............................................58
Table 16. Overview of studies of medical interventions ..............................................................60
Table 17. Outcomes of RCTs of antipsychotic medications for challenging and repetitive
behaviors ........................................................................................................................................63
Table 18. Outcomes of studies of SRIs for the treatment of repetitive and challenging behaviors
in ASDs .........................................................................................................................................68
Table 19. Harms frequently reported in studies of medical interventions ....................................70
Table 20. Outcomes of studies of stimulants for the treatment of hyperactivity in ASDs ...........72
Table 21. Outcomes of RCTs of dietary supplements for the treatment of ASDs ........................74
Table 22. Outcomes of RCTs of additional medical interventions for the treatment of ASDs ....75
Table 23. Overview of allied health studies ..................................................................................78
Table 24. Outcomes of RCTs of auditory/music interventions for the treatment of ASDs ..........82
Table 25. Overview of CAM studies ............................................................................................85
Table 26. Outcomes of interventions for children at risk for diagnosis of ASDs .........................97
Table 27. Summary of results of studies of early intensive behavioral and developmental
approaches....................................................................................................................................101
Table 28. Summary of results of social skills interventions ........................................................103
Table 29. Summary of results of studies of play-/interaction-based interventions......................104
Table 30. Summary of results of studies targeting behaviors commonly associated
with ASDs ....................................................................................................................................105
Table 31. Summary of results of studies of other behavioral interventions ................................106
Table 32. Summary of results of educational interventions ........................................................107
Table 33. Summary of results of medical studies ........................................................................108
Table 34. Summary of results of allied health studies .................................................................111
Table 35. Summary of results of CAM studies............................................................................112
Table 36. Intervention, strength of evidence domains, and strength of evidence
for key outcomes ..........................................................................................................................113
Table 37. Interventions/outcomes with insufficient strength of evidence
by outcomes assessed ...................................................................................................................114
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