Effective Health Care Program
Comparative Effectiveness ReviewNumber 65
Interventions forAdolescents and YoungAdults With AutismSpectrum Disorders
Comparative Effectiveness Review
Number 65
Interventions for Adolescents and Young Adults 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:
Julie Lounds Taylor, Ph.D.
Dwayne Dove, M.D.
Jeremy Veenstra-VanderWeele, M.D.
Nila A. Sathe, M.A., M.L.I.S.
Melissa L. McPheeters, Ph.D., M.P.H.
Rebecca N. Jerome, M.L.I.S., M.P.H.
Zachary Warren, Ph.D.
AHRQ Publication No. 12-EHC063-EF
August 2012
This report is based on research conducted by the Vanderbilt Evidence-based Practice Center
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 content, and do not necessarily represent the views of
AHRQ. 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 the application of 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 the 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 or actions 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 that are clearly noted in the document. Further reproduction of those
copyrighted materials is prohibited without the specific permission of copyright holders.
Persons using assistive technology may not be able to fully access information in this report. For
assistance contact EffectiveHealthCare@ahrq.hhs.gov.
None of the investigators has any affiliations or financial involvement that conflicts with the
material presented in this report.
Suggested citation: Lounds Taylor J, Dove D, Veenstra-VanderWeele J, Sathe NA, McPheeters
ML, Jerome RN, Warren Z. Interventions for Adolescents and Young Adults With Autism
Spectrum Disorders. Comparative Effectiveness Review No. 65. (Prepared by the Vanderbilt
Evidence-based Practice Center under Contract No. 290-2007-10065-I.) AHRQ Publication No.
12-EHC063-EF. Rockville, MD: Agency for Healthcare Research and Quality. August 2012.
www.effectivehealthcare.ahrq.gov/reports/final.cfm.
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 strength 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
www.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 from 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 email list to learn about new program products and opportunities for input.
Comparative Effectiveness Reviews will be updated regularly.
We welcome comments on this CER. They may be sent by mail to the Task Order Officer
named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD
20850, or by email to epc@ahrq.hhs.gov.
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. Shilpa Amin, M.D., MBsc, FAAFP
Director Task Order Officer
Evidence-based Practice Program Center for Outcomes and Evidence
Center for Outcomes and Evidence Agency for Healthcare Research and Quality
Agency for Healthcare Research and Quality
Acknowledgments
The authors gratefully acknowledge the following individuals for their contributions to this
project:
Dr. Adeola Davis assisted with reviewing abstracts and full-text articles and data extraction.
We appreciate her willingness to take on whatever was asked of her.
Dr. Shanthi Krishnaswami lent her keen eye for detail to data extraction and reviews of
abstracts and full text articles. We also appreciate her thoughtful input into methodological
discussions.
Ms. Kathy Lee provided helpful assistance in locating articles and preparing materials for
meetings.
Ms. Sanura Latham and Ms. Leah Vance assisted with formatting tables and appendices and
lent their support to logistical elements of the review.
Key Informants
Somer L. Bishop, Ph.D.
Cincinnati Children’s Hospital
Cincinnati, OH
Edwin H. Cook, Jr., M.D.
University of Illinois, Chicago
Chicago, IL
Jim Perrin, M.D.
Massachusetts General Hospital
Boston, MA
Marcia Mailick Seltzer, Ph.D.
Waisman Center
Madison, WI
Fred R. Volkmar, M.D.
Yale Child Study Center
New Haven, CT
Technical Expert Panel
Somer L. Bishop, Ph.D.
Cincinnati Children’s Hospital
Cincinnati, OH
Daniel Coury, M.D.
Ohio State University
Columbus, OH
Edwin H. Cook, Jr., M.D.
University of Illinois, Chicago
Chicago, IL
Patricia Howlin, Ph.D.
Institute of Psychiatry
London, United Kingdom
Jim Perrin, M.D.
Massachusetts General Hospital
Boston, MA
Peter Szatmari, M.D., M.Sc.
McMaster University
Hamilton, Ontario, Canada
Peer Reviewers
Somer L. Bishop, Ph.D.
Cincinnati Children’s Hospital
Cincinnati, OH
Edwin H. Cook, Jr., M.D.
University of Illinois, Chicago
Chicago, IL
Patricia Howlin, Ph.D.
Institute of Psychiatry
London, United Kingdom
Doris Lotz, M.D.
New Hampshire Department of Health and
Human Services
Concord, NH
Gary Mesibov, Ph.D.
University of North Carolina
Chapel Hill, NC
Jim Perrin, M.D.
Massachusetts General Hospital
Boston, MA
Lawrence Scahill, Ph.D.
Yale University
New Haven, CT
Tristram Smith, Ph.D.
University of Rochester
Rochester, NY
Peter Szatmari, M.D., M.Sc.
McMaster University
Hamilton, Ontario, Canada
Interventions for Adolescents and Young Adults With
Autism Spectrum Disorders
Structured Abstract
Objectives. We systematically reviewed evidence on therapies for adolescents and young adults
(ages 13 to 30) with autism spectrum disorders (ASD). We focused on the outcomes, including
harms and adverse effects, of interventions addressing the core symptoms of ASD; common
medical and mental health comorbidities occurring with ASD; the attainment of goals toward
functional/adult independence; educational and occupational/vocational attainment; quality of
life; access to health and other services; and the transitioning process (i.e., process of
transitioning to greater independent functioning). We also addressed the effects of interventions
on family outcomes including parent distress and satisfaction with interventions.
Data sources. We searched MEDLINE® via PubMed, PsycINFO®, the Educational Resources
Information Clearinghouse, and the Cumulative Index of Nursing and Allied Health Literature
databases as well as the reference lists of included studies.
Review Methods. We included studies published in English from January 1980 to December
2011. We excluded intervention studies with fewer than 20 adolescents or young adults with
ASD or fewer than 20 parents or family members of such individuals and studies lacking
relevance to ASD treatment.
Results. We identified 32 unique studies, most of which were poor quality. Five studies, mostly
of medical interventions, were fair quality, and none were good. In the behavioral literature,
studies of group- and computer-based interventions reported short-term gains in social skills.
Two poor-quality studies of educational interventions reported some gains in vocabulary and
reading. Four small studies investigated disparate interventions addressing highly specific
adaptive/life skills with some positive results in studies typically of short duration. Studies of
vocational interventions, all of poor quality, reported that on-the job supports may promote
employment in the community. Little evidence supports the use of medical interventions in
adolescents and young adults with ASD; however, antipsychotic medications and serotonin
reuptake inhibitors were associated with improvements in specific challenging behaviors.
Similarly, little evidence supports the use of allied health interventions including facilitated
communication.
Conclusions. Few studies have been conducted to assess treatment approaches for adolescents
and young adults with ASD, and as such there is very little evidence available for specific
treatment approaches in this population; this is especially the case for evidence-based approaches
to support the transition of youth with autism to adulthood. Of the small number of studies
available, most were of poor quality, which may reflect the relative recency of the field. Five
studies, primarily of medical interventions, had fair quality. Behavioral, educational, and
adaptive/life skills studies were typically small and short term and suggested some potential
improvements in social skills and functional behavior. Small studies suggested that vocational
programs may increase employment success for some individuals. Few data are available to
support the use of medical or allied health interventions in the adolescent and young adult
population. The medical studies that have been conducted focused on the use of medications to
address specific challenging behaviors, including irritability and aggression, for which
effectiveness in this age group is largely unknown and inferred from studies including mostly
younger children.
Contents
Executive Summary .................................................................................................................ES-1
Introduction ...................................................................................................................................1
Need for Evidence Regading Treatment of Autism Spectrum Disorders in Adolescents
and Young Adults ................................................................................................................1
Interventions Used To Treat ASD .............................................................................................2
Behavioral Interventions ......................................................................................................2
Educational Interventions ....................................................................................................3
Vocational Interventions ......................................................................................................3
Adaptive/Life Skills Interventions .......................................................................................3
Medical and Related Interventions ......................................................................................4
Allied Health Interventions ..................................................................................................4
Importance of this Review .........................................................................................................5
Scope and Key Questions ..........................................................................................................5
Scope of This Report ...........................................................................................................5
Key Questions ......................................................................................................................5
Organization of This Evidence Report ......................................................................................6
Uses of This Report ...................................................................................................................6
Methods ..........................................................................................................................................8
Topic Development and Refinement .........................................................................................8
Role of the AHRQ Task Order Officer ................................................................................8
Analytic Framework ..................................................................................................................8
Literature Search Strategy........................................................................................................10
Databases ...........................................................................................................................10
Regulatory Information ......................................................................................................10
Search Terms .....................................................................................................................10
Process for Study Selection .....................................................................................................11
Inclusion and Exclusion Criteria ........................................................................................11
Screening of Studies ................................................................................................................13
Categorization of Interventions................................................................................................13
Data Extraction and Data Management ...................................................................................14
Individual Study Quality Assessment ......................................................................................14
Determining Quality Levels ...............................................................................................15
Data Synthesis ..........................................................................................................................15
Grading the Body of Evidence for Each Key Question ...........................................................15
Applicability ............................................................................................................................17
Peer Review and Public Commentary .....................................................................................17
Results ..........................................................................................................................................18
Article Selection......................................................................................................................18
Organization of Results............................................................................................................19
Overview of the Literature .......................................................................................................19
Studies of Behavioral Interventions .........................................................................................20
Key Points ..........................................................................................................................20
Overview of the Literature .................................................................................................21
Detailed Analysis ...............................................................................................................21
Studies of Educational Interventions .......................................................................................26
Key Points ..........................................................................................................................26
Overview of the Literature .................................................................................................26
Detailed Analysis ...............................................................................................................26
Studies of Adaptive/Life Skills Interventions ..........................................................................28
Key Points ..........................................................................................................................28
Overview of the Literature .................................................................................................28
Detailed Analysis ...............................................................................................................29
Studies of Vocational Interventions .........................................................................................32
Key Points ..........................................................................................................................32
Overview of the Literature .................................................................................................32
Detailed Analysis ...............................................................................................................32
Studies of Medical Interventions .............................................................................................37
Key Points ..........................................................................................................................37
Overview of the Literature .................................................................................................37
Detailed Analysis ...............................................................................................................38
Studies of Allied Health Interventions .....................................................................................49
Key Points ..........................................................................................................................49
Overview of the Literature .................................................................................................49
Detailed Analysis ...............................................................................................................49
Discussion.....................................................................................................................................54
State of the Literature...............................................................................................................54
Summary of Outcomes ............................................................................................................54
Studies of Behavioral Interventions ...................................................................................54
Studies of Educational Interventions .................................................................................54
Studies of Adaptive/Life Skills Interventions ....................................................................55
Studies of Vocational Interventions ...................................................................................55
Studies of Medical Interventions .......................................................................................55
Studies of Allied Health Interventions ...............................................................................57
Strength of the Evidence for Effectiveness of Therapies .........................................................57
Overview ............................................................................................................................57
Applicability ............................................................................................................................61
Applicability of the Evidence ............................................................................................61
Gaps in the Evidence ...............................................................................................................64
Methodologic Considerations ............................................................................................64
Future Research .................................................................................................................65
Conclusions ..............................................................................................................................67
References ....................................................................................................................................68
Acronyms and Abbreviations .....................................................................................................73
Tables
Table A. Description of Study Quality Levels...........................................................................ES-6
Table B. Summary of Strength of Evidence and Key Outcomes of Studies ...........................ES-11
Table 1. Inclusion and Exclusion Criteria ......................................................................................11
Table 2. Description of Study Quality Levels ...............................................................................15
Table 3. Domains Used To Assess Strength of Evidence ..............................................................16
Table 4. Overview of the Literature Addressing Interventions for Adolescents and Young
Adults with ASD ......................................................................................................................20
Table 5. Key Outcomes of Behavioral Studies Addressing the Core Symptoms of ASD.............23
Table 6. Key Outcomes of Educational Interventions Addressing Core Symptoms of ASD .......27
Table 7. Key Outcomes of Educational Interventions Addressing Independent Functioning .......28
Table 8. Summary of Outcomes of Adaptive/Life-Skills Interventions ........................................30
Table 9. Key Outcomes of Vocational Studies Addressing Core Symptoms ................................34
Table 10. Key Outcomes of Vocational Studies Addressing Independent Functioning................36
Table 11. Key Outcomes of Studies Assessing Antipsychotics ....................................................40
Table 12. Key Outcomes of Studies Assessing Opioid Receptor Antagonists ..............................42
Table 13. Key Outcomes of Studies Assessing SRIs .....................................................................45
Table 14. Key Outcomes of Studies of Allied Health Interventions Addressing Core
Symptoms of ASD ...................................................................................................................51
Table 15. Summary of Outcomes of Studies of Allied Health Interventions Addressing
Independent Functioning .........................................................................................................53
Table 16. Intervention, Strength of Evidence Domains, and Strength of Evidence
for Outcomes of Behavioral studies .........................................................................................58
Table 17. Intervention, Strength of Evidence Domains, and Strength of Evidence
for Outcomes of Educational Studies ......................................................................................58
Table 18. Intervention, Strength of Evidence Domains, and Strength of Evidence
for Outcomes of Adaptive/Life Skills Studies .........................................................................59
Table 19. Intervention, Strength of Evidence Domains, and Strength of Evidence
for Outcomes of Vocational Studies ........................................................................................59
Table 20. Intervention, Strength of Evidence Domains, and Strength of Evidence
for Outcomes of Medical Studies ............................................................................................60
Table 21. Intervention, Strength of Evidence Domains, and Strength of Evidence
for Outcomes of Allied Health Studies ....................................................................................61
Figures
Figure A. Analytic Framework for Interventions for Adolescents and Young Adults
With ASD............................................................................................................................ES-4
Figure B. Disposition of Studies Identified for This Review ....................................................ES-7
Figure 1. Analytic Framework for Interventions for Adolescents and Young Adults
With ASD..................................................................................................................................9
Figure 2. Disposition of Studies Identified for this Review ..........................................................18
Appendixes
Appendix A. Exact Search Strings and Results
Appendix B. Categorization of Study Designs
Appendix C. Sample Data Extraction Forms
Appendix D. Evidence Tables
Appendix E. Quality Assessment Form
Appendix F. Excluded Studies
Appendix G. Quality of the Literature
Executive Summary
Background
Autism Spectrum Disorders (ASD) are among the most common neurodevelopmental
disorders, with an estimated prevalence of 1 in 110 children in the United States having an
ASD.1 ASDs are typically diagnosed in early childhood, often at or before preschool age. The
diagnosis is fundamentally behaviorally based (i.e., there is no specific genetic test or clinical/
laboratory procedure for diagnosis) and rests on documented core impairments related to social
interaction, communication, as well as restricted and repetitive behavior.
Diagnoses made by clinical providers, often pediatricians, behavioral providers, child
neurologists, child psychiatrists, or child psychologists, are based on documented symptom
patterns in these domains. Numerous screening and diagnostic tools are available to help
document and measure symptoms of autism, with research investigations increasingly utilizing
such measures in combination with clinical diagnoses in order to more accurately describe,
measure, and analyze the heterogeneity in presentation associated with ASD. In addition to
impairments in core symptom areas, many individuals with ASD also have impaired cognitive
skills, atypical sensory behaviors, or other complex medical and psychiatric symptoms and
conditions, such as seizure disorders, motor impairments, hyperactivity, anxiety, and self-
injury/aggression.
More than 55,000 individuals between the ages of 15 and 17 in the United States likely have
an ASD.2 For some individuals, core symptoms of ASD (impairments in communication and
social interaction and restricted/repetitive behaviors and interests) may improve with intervention
and over time3-5; however, some degree of impairment typically remains throughout the
lifespan.6 As children transition to adolescence and young adulthood, developmentally
appropriate interventions to ameliorate core deficits may continue, but the focus of treatment
often shifts toward promoting adaptive behaviors that can facilitate and enhance independent
functioning.6 Treatments for some must take into account new emergent symptoms as well as
engagement with new developmental challenges (e.g., independent living, vocational
engagement, postsecondary education).
There is also evidence to suggest that improvements in symptoms and improvements in
problem behaviors may slow down or stop after youth with ASD leave high school.7 This change
in improvement is likely due, at least in part, to the termination of services received through the
secondary school system upon high school exit, as well as the lack of adult services and long
waiting lists for many services.7, 8 This issue of the lack of services available to help young
adults with ASD transition to greater independence has been noted by researchers for a number
of years and is increasingly a topic in the lay media.9
Interventions Used To Treat ASD
Individuals with ASD have significant impairments in social interaction, communication, and
repetitive behavior. As noted, some people with ASD also have impaired cognitive skills,
atypical sensory behaviors, or other complex medical and psychiatric symptoms and conditions.
The expression and severity of ASD symptoms differ widely across individuals and over time.
Treatments may include a range of behavioral, psychosocial, educational, medical, and
complementary approaches focused on the transitional process and improving outcomes for
parents/families of individuals with ASD during adolescence and adulthood.
ASD in Adolescence and Young Adulthood
Current data suggest that attainment of independent living or employment in adulthood for
individuals with an ASD is variable, with factors that predict the ability to live and work
independently not well elucidated.6 Research conducted to date has suggested that most
individuals with ASD will require some sort of intervention, often at very intensive levels,
throughout adolescence and adulthood, and the estimated costs of medical and nonmedical care
(e.g., special education, daycare) are high. One study estimates that the total yearly societal per
capita cost of caring for and treating a person with autism in the United States at $3.2 million and
at about $35 billion for an entire birth cohort of individuals with autism.10 A study of health care
utilization in a large group health plan revealed increased medication costs in older children with
an ASD compared with younger children, as well as similarly aged adolescents without an ASD;
other care costs were also higher in this population, including a significantly increased rate of
hospitalizations.11
Costs of transitional and employment programs are also high for young adults with ASD. In a
recent analysis of U.S. Federal- and State-funded vocational rehabilitation programs, enrolled
individuals with ASD were among the most costly of nine disability groups, with costs even
higher among those with ASD and another concomitant disability. However, those with ASD
had a higher rate of employment (40.8%) at the time of case closure compared with those with
other disabilities, though with fewer work hours and lower wages than some other disability
groups.12
There is no cure for ASD and no global consensus regarding which intervention strategies are
most effective. Chronic management, often using multiple treatment approaches, may be
required to maximize ultimate functional independence and quality of life by minimizing core
ASD features, facilitating development and learning, promoting socialization, reducing
maladaptive behaviors, and educating and supporting families. Investigators have noted that less
data on therapies for adolescents or young adults exist than for younger children,13 and such
research is increasingly important as the prevalence of ASD continues to grow and as children
with ASD diagnoses reach adolescence.
Objectives
The goal of this review is to examine the effects of available interventions on adolescents and
young adults with ASD, focusing on the following outcomes: core symptoms of ASD
(impairments in social interaction, communication, and repetitive behavior); medical and mental
health comorbidities; functional behaviors and independence; the transition to adulthood; and
family outcomes.
Population
We focused this review on therapies for adolescents and young adults (ages 13 to 30) with
ASD as well as interventions aimed at family members.
Interventions
Studies assessed interventions falling into the broad categories of behavioral, educational,
adaptive/life skills, vocational, medical, and allied health approaches.
Comparators
Comparators included no treatment, placebo, and comparative interventions or combinations
of interventions.
Outcomes
Intermediate outcomes included changes in core ASD symptoms and in common medical and
mental health comorbidities as well as effects on functional behavior, the transition process, and
family outcomes. Long-term outcomes included changes in adaptive/functional independence,
academic and occupational attainment or engagement, psychological well-being, and
psychosocial adaptation. We also assessed the harms of interventions, defined by the Agency for
Healthcare Research and Quality (AHRQ) Effective Health Care program as all possible adverse
consequences of an intervention, including adverse events (Figure A).14
Key Questions
We have synthesized evidence in the published literature to address these Key Questions:
• Key Question 1: Among adolescents and young adults with ASD, what are the effects of
available interventions on the core symptoms of ASD?
• Key Question 2: Among adolescents and young adults with ASD, what are the effects of
available interventions on common medical and mental health comorbidities (e.g.,
epilepsy, sleep disorders, motor impairments, obesity, depression, anxiety, acute and
episodic aggression, attention deficit hyperactivity disorder, etc.)?
• Key Question 3: Among adolescents and young adults with ASD, what are the effects of
available interventions on functional behavior, attainment of goals toward independence,
educational attainment, occupational/vocational attainment, life satisfaction, access to
health and other services, legal outcomes, and social outcomes?
• Key Question 4: Among adolescents and young adults with ASD, what is the
effectiveness of interventions designed to support the transitioning process, specifically
to affect attainment of goals toward independence, educational attainment,
occupational/vocational attainment, life satisfaction, access to health and other services,
legal outcomes, and social outcomes?
• Key Question 5: Among adolescents and young adults with ASD, what harms are
associated with available interventions?
• Key Question 6: What are the effects of interventions on family outcomes?
Analytic Framework
The analytic framework summarizes the process by which individuals with ASD and their
families/caregivers make and modify treatment choices (Figure A). Treatment choices may target
intermediate outcomes including changes in communication skills, academic skill development,
or social skills. Interventions lead to long-term outcomes such as adaptive independence and
changes in psychosocial well-being. Family outcomes such as parent distress may also be
targeted by interventions and may lead in turn to long-term outcomes. Finally, interventions may
be associated with harms/adverse effects. Numbers in circles within the diagram indicate the
placement of Key Questions in relation to the treatment process.
The analytic framework summarizes the process by which individuals with autism spectrum disorders (ASD) and their families/caregivers make and modify treatment choices. Treatment choices may target intermediate outcomes including changes in communication skills, academic skill development, or social skills. Interventions lead to long-term outcomes such as adaptive independence and changes in psychosocial well-being. Family outcomes such as parent distress may also be targeted by interventions and may lead in turn to long-term outcomes. Finally, interventions may be associated with harms/adverse effects. Numbers in circles within the diagram indicate the placement of Key Questions in relation to the treatment process.
Figure A. Analytic framework for interventions for adolescents and young adults with ASD
KQ = Key Question
Methods
Input From Stakeholders
The topic was nominated in a public process. With key informant input, we drafted initial
Key Questions, which were reviewed by AHRQ and posted to a public Web site for public
comment. Using public input, we drafted final Key Questions, which were reviewed by AHRQ.
We convened a Technical Expert Panel to provide input during the project on issues such as
setting inclusion/exclusion criteria and assessing study quality. In addition, the draft report was
peer reviewed and available for public comment.
Data Sources and Selection
Data Sources
We searched four databases: MEDLINE® via the PubMed interface, PsycINFO® (psychology
and psychiatry literature), the Educational Resources Information Clearinghouse, and the
Cumulative Index of Nursing and Allied Health Literature database. We used a combination of
controlled vocabulary terms appropriate for each database (e.g., MEDLINE vocabulary term
autistic disorder) and keywords related to ASD (e.g., Asperger syndrome). Appendix A of the
full report details each search strategy. We hand searched reference lists of included articles and
recent reviews for additional studies.
Inclusion and Exclusion Criteria
We included all study designs except single case reports provided that studies reported on an
intervention aimed at individuals with ASD between the ages of 13 and 30 or family members of
such individuals. We excluded studies that:
• Were not original research
• Did not report information pertinent to the Key Questions
• Did not address treatment modalities aimed at core symptoms of ASD, common
comorbidities, functional/life skills outcomes, family-related outcomes, or assisting with
the transition to adulthood
• Did not include aggregate data (i.e., included only individual data for each participant) or
data presented only in graphics/figures
• Were single case reports
• Were not published in English
• Were published before 1980 and the publication of autism diagnostic criteria in the
Diagnostic and Statistical Manual of Mental Disorders, Third Edition.
We also excluded studies that included fewer than 20 total participants in the target age range
with ASD or family members of such individuals. Our goal was to identify and review the best
evidence for assessing the efficacy and effectiveness of therapies for adolescents and young
adults with ASD, with an eye toward utility in the treatment setting.
Interventions to address ASDs are frequently behavioral in nature and highly intensive. They
are also frequently adapted to be targeted to specific study participants given the significant
heterogeneity of individuals with ASD. In part because this makes behavioral research complex
and intensive, study sizes tend to be very small. A cutoff sample size of 20 provides a balance,
allowing us to review and comment on adequate literature for the review but with studies large
enough to suggest effects of the interventions.
Screening of Studies
Two reviewers separately evaluated each abstract. If one reviewer concluded that the article
could be eligible, we retained it. Two reviewers independently read the full text of each included
article to determine eligibility, with disagreements resolved via third-party adjudication.
Data Extraction and Quality Assessment
Data Extraction
All team members entered information into the evidence tables. After initial data extraction,
a second team member edited entries for accuracy, completeness, and consistency. In addition to
outcomes for treatment effectiveness and family outcomes, we extracted data on harms/adverse
effects.
Quality Assessment
Two reviewers independently assessed quality (study design, diagnostic approach, participant
ascertainment, intervention characteristics, outcomes measurement, and statistical analysis) using
a quality assessment methodology adapted from that used in a prior AHRQ review of therapies
for children with ASD.15 We resolved differences though discussion, review of the publications,
and consensus with the team. We rated studies as good, fair, or poor quality and retained poor
studies as part of the evidence base discussed in this review. More information about our quality
assessment methods is in the full report, and Table A describes the quality ratings.
Table A. Description of study quality levels
Quality
Level
Description
Good
Good studies are considered to have the least bias and results are considered valid. A good study has a
clear description of the population, setting, interventions, and comparison groups; uses a valid approach
to allocate patients to treatments; has a low dropout rate; and uses appropriate means to prevent bias;
measure outcomes; analyze and report results.
Fair
Fair studies are susceptible to some bias, but probably not sufficient to invalidate the results. A study may
be missing information, making it difficult to assess limitations and potential problems. As the “fair quality”
category is broad, studies with this rating vary in their strengths and weaknesses. The results of some
fair-quality studies are possibly valid, while others are probably valid.
Poor
Poor studies are subject to significant bias that may invalidate the results. These studies have serious
errors in design, analysis, or reporting; have large amounts of missing information; or have discrepancies
in reporting. The results of a poor-quality study are at least as likely to reflect flaws in the study design as
to indicate true differences between the compared interventions.
Data Synthesis and Analysis
Evidence Synthesis
We used summary tables to synthesize studies and summarized the results qualitatively.
Strength of the Evidence
The degree of confidence that the observed effect of an intervention is unlikely to change is
presented as strength of evidence. Strength of evidence can be regarded as insufficient, low,
This figure outlines the flow of articles identified for the review. We located a total of 4,855 citations. Of these, 1,035 required full-text review. Of the 1,035 full text articles reviewed, we retained 32 papers (comprising 32 unique studies) and excluded 1,003 papers. Papers could be excluded for multiple reasons, and a number were excluded because they were not relevant to the Key Questions (n=840), did not include individuals with ASD in our target age range of 13 to 30 years (n=834), did not include at least 20 adolescents or young adults with ASD or their family members (n=845), or were not original research (n=156).
moderate, or high. It describes the adequacy of the current research, in quantity and quality, and
the degree to which the entire body of current research provides a consistent and precise estimate
of effect. We established methods for assessing the strength of evidence based on the AHRQ
Effective Health Care program’s Methods Guide for Effectiveness and Comparative
Effectiveness Reviews.16
Results
Article Selection
Of the entire group of 4,855 citations, 1,035 articles required full-text review (Figure B). Of
the 1,035 full-text articles reviewed, we retained 32 papers (comprising 32 unique studies) and
excluded 1,003 papers.
Figure B. Disposition of studies identified for this review
KQ = Key Question; n = number
aOne paper17 reports two unique studies
bNumbers do not tally, as studies could be excluded for multiple reasons
Organization of Results
As noted, we classified studies by broad category of intervention (behavioral, educational,
vocational, adaptive/life skills, medical, and allied health). With the exceptions of studies of
behavioral, medical, and vocational interventions, which included at least two studies addressing
the same intervention, the other categories of interventions largely comprised single studies of
unique interventions. Most studies (n=14) also targeted core symptoms of ASD (Key Question
(1) or functional behavior/independent living skills (n=10) (Key Question (3). Nine studies, eight
of which addressed medical interventions, examined comorbidities commonly occurring with
ASD, which we defined broadly to encompass associated symptoms such as irritability (Key
Question (2). Only studies of medical interventions addressed harms (Key Question 5).
One study addressed interventions targeting the transition process (Key Question 4), and two
studies assessed effects of an intervention on family outcomes (Key Question 6). Because
questions were addressed by a number of small, single studies of a given intervention, we discuss
all studies together in the following sections instead of divided by Key Question. This approach
allows us to present the findings of this disparate literature more clearly.
Across all categories of interventions, most studies (n=27) were of poor quality, and none
was good quality. Five RCTs were fair quality: four that investigated pharmacologic agents18-21
and one allied health study that assessed a leisure/recreation program.22 Although positive results
may be reported in individual studies, the poor quality of the studies and the lack of replication
of the intervention studies mean that the strength of evidence for the body of evidence around
any specific intervention is currently insufficient.
More research is needed to determine a measure of effect associated with any of the
interventions described in this body of literature. Therefore, although we describe the results of
individual studies in the report, the overall strength of evidence that any given intervention has a
specific effect on outcomes is insufficient.
Studies of Behavioral Interventions
We identified eight studies17, 23-28 of behavioral interventions. One paper17 reports two unique
studies. Studies were conducted in the United States, Europe, and Canada and included a total of
302 participants. Seven studies (with two unique studies reported in one paper17) examined
individual/group- or computer-based social skills interventions17, 23-25, 27, 28 and an additional
study assessed an intensive behavioral treatment provided at a semi-residential facility.26 All
studies were of poor quality. Individual studies assessing heterogeneous social skills approaches
reported some benefits in emotion recognition, social functioning, and participation in social
activity over the short term.17, 23-25, 27, 28 The study of an intensive approach reported modest
improvements in adaptive behavior over a 2-year period.26 This study also assessed parental
satisfaction with treatment, noting high levels of satisfaction overall.
Studies of Educational Interventions
Two studies, both poor quality, examined educational interventions.29, 30 Studies were
conducted in the United States and Canada and included fewer than 50 total individuals with
ASD. In one study, individuals with ASD and mean mental age scores of 3.3 years received
language instruction using two teaching methods, with no significant difference observed
between methods.29 In a randomized study assessing strategies to promote reading
comprehension,30 scores generally improved overall in the short term.
Studies of Adaptive/Life Skills Interventions
We identified four studies, all of poor quality, of various interventions focused on adaptive
behavior.31-34 Treatment duration varied tremendously from a daylong experiment to a study
examining outcomes across a 2-year interval in a residential facility. Overall these studies
included a total of 155 individuals with ASD. All studies were conducted in the United States,
and at least two explicitly included participants with intellectual disability.31, 33Across studies,
participants made very specific short-term gains in learning or successfully executing an adaptive
or life skills-focused task, including lacing shoes or using a personal digital assistant to help with
remembering activities. In one study of a residential facility employing a Treatment and
Education of Autistic and related Communication Handicapped Children (TEACCH)-based
model, exploratory analyses showed variable results with few significant changes in skills or
negative behaviors over time across individuals in the TEACCH program or in institutions,
family homes, or group homes.31 Parents were significantly more satisfied with the TEACCH
program overall.
A final poor-quality case series addressed the transitioning process by assessing effects
related to implementing a classroom process—changing rooms throughout the school day—that
individuals would likely encounter as they move to high school or college; the study reported no
increase in disruptive behavior after the implementation of classroom rotation.34
Studies of Vocational Interventions
We identified six papers from five unique study populations that addressed the impact of
supported employment/vocational interventions.8, 35-39 Studies were conducted in the United
States and Europe and included more than 1,900 individuals with ASD; roughly 1,700 of these
were included in an administrative database study assessing use of vocational rehabilitation
services. All studies were considered poor quality. Interventions all involved finding and
implementing on-the-job supports (broadly defined as services to promote job placement and job
retention) for young adults with ASD. Studies comparing supported employment in the
community with sheltered workshops reported that participants in supported employment groups
experienced reductions in autism symptoms and improvements in quality of life in one study
assessing those outcomes,37, 38 and improvements in measures of cognition in another study.35
In long-term studies of a job-finding program in the United Kingdom,8, 39 young adults in a
supported employment group were significantly more likely to find paid employment than those
in the control group (63.3% vs. 25%), with the majority of those employed showing job
satisfaction. One final study identified individuals with ASD in a U.S. vocational rehabilitation
dataset. These data illustrated that the presence of on-the-job supports was associated with a
higher likelihood of employment in the community (competitive or supported).36
Studies of Medical Interventions
Eight studies of pharmacologic agents, four of fair18-21 and four of poor quality,40-43met our
review criteria. The studies included a total of 272 individuals with ASD, and all were conducted
in the United States, Canada, or Europe in academic clinics. All studies were funded using
institutional and grant sources. Three randomized controlled trials (RCTs), one fair quality21 and
two poor,20, 40 addressed the efficacy of antipsychotic medications including risperidone and
haloperidol. One fair-quality RCT investigated the opiate antagonist naltrexone.19 Of five studies
examining serotonin reuptake inhibitors (SRIs),18, 20, 41-43 two RCTs were fair quality,18, 20 and
three case series were poor.41-43
All studies of medical interventions addressed outcomes related to comorbid conditions such
as irritability or harms of treatments. Studies of antipsychotic medications reported some
reductions in repetitive behavior, aggression, hyperactivity, and irritability in treatment groups
over time periods of 7 to 24 weeks. Brief treatment with naltrexone (4 weeks) was associated
with increases in stereotypy (repetitive or ritualistic behavior or movement) in the treated group.
Studies of SRIs reported some improvements in treated participants in measures of irritability,
repetitive behavior, and aggression over treatment durations of 7 to 12 weeks. One longer term
case series reported improvements in general symptom severity and compulsive behavior in
individuals receiving fluoxetine for a mean of 6 months.43
All medical studies reported harms of treatment. Harms or adverse effects reported in studies
of antipsychotic medications included sedation, gastrointestinal complaints, weight gain,
increased appetite, fatigue, dystonia, and depression.21, 40, 44 Adverse effects described in the
study of naltrexone included nausea, fatigue, sedation, and an increase in self-injurious behavior
and stereotypy.19 Harms noted in studies of SRIs included fatigue, tremor, tachycardia, agitation,
gastrointestinal complaints, sedation, anxiety, agitation, and insomnia.18, 20, 41-43
Studies of Allied Health Interventions
We identified five studies of disparate allied health interventions22, 45-48 including one fair-
quality RCT investigating a leisure/recreation program,22 two poor-quality case series addressing
music therapy,47, 48 and two poor case series addressing facilitated communication.45, 46 Studies
included a total of 174 individuals with ASD, and the duration of treatment ranged from 20 hours
to 12 months in 4 studies;22, 45, 46, 48 one study of music therapy reviewed data from participants
who had participated in varying hours of therapy.47 Studies of music therapy reported some
improvements in social skills using unvalidated measures.47, 48 Studies assessing facilitated
communication noted little communication improvement associated with facilitation and some
evidence of facilitator influence on participants’ responses.45, 46 The study examining a recreation
program reported improvements in stress-related scores for individuals in the intervention group
compared with those in the control group (p<0.001). Overall quality of life scores similarly
improved for intervention participants compared with the control group.22
Discussion
Key Findings
Despite a growing population of adolescents and young adults who have diagnoses of an
ASD and the need for effective intervention across the lifespan, very little research is available to
help understand the impact of specific intervention approaches for adolescents and young adults
with ASD. The available research is lacking in scientific rigor. We identified a total of 32 studies
(one paper reported two separate studies), of which 10 were randomized controlled trials.
Although RCTs are often considered the gold standard for assessing intervention effectiveness,
particularly in a complex behavioral field with emerging research such as this, observational
designs can be rich sources of information. Nonetheless, most studies were of poor quality; only
five were fair quality and none were good quality. The strength of the evidence (degree of
confidence that the observed effect of an intervention is unlikely to change) across all
interventions and outcomes was insufficient as studies were typically of poor quality, addressed
disparate interventions and outcomes, and lack replication (Table B).
Table B. Summary of strength of evidence and key outcomes of studies
Intervention
Strength
of
Evidence
Summary/Conclusions/Comments
Behavioral
Individual or group-
based social skills
training23, 24, 27, 28
Insufficient
• 4 poor-quality studies, 2 reporting on manualized (i.e., has a published treatment
manual) intervention.
• Some gains in social skills on largely parent-reported measures in short-term
studies.
• 2 studies lacked comparison groups; diagnostic approach, participant
characteristics, treatment fidelity not clearly reported.
Computer-based
social skills
training17, 25
Insufficient
• 3 poor-quality, short-term studies (one paper17 reported 2 separate studies).
• Some improvements in emotion recognition in treated participants; no differences
in measures of generalization.
• Systematic diagnostic approach not reported within studies; concomitant
interventions and treatment fidelity not reported.
Intensive behavioral
treatment 26
Insufficient
• 1 poor-quality case series with diverse participants.
• Some gains in adaptive behavior reported.
• Intervention not clearly described; treatment fidelity and concomitant interventions
not reported; assessors not masked.
Educational
Vocabulary
teaching29
Insufficient
• 1 poor-quality nonrandomized trial.
• Neither teaching method significantly more effective in increasing nouns.
• Inclusion/exclusion criteria not clearly stated; attrition and differences in
concomitant interventions not reported; assessors not masked.
Reading
comprehension30
Insufficient
• 1 poor quality RCT; two facilitation methods increased comprehension compared
with baseline scores.
• Randomization method not clearly reported; assessors not masked and
differences in concomitant interventions not reported.
Adaptive/Life Skills
Specific
life/transitional
skills32-34
Insufficient
• 3 poor-quality, short-term studies assessing highly specific skills and unique
interventions (shoe lacing, digital device use, rotating classroom schedule).
• Some gains seen in individual studies but most lacked comparison groups.
• Systematic diagnostic approach not reported within studies; participants often not
clearly characterized; differences in concomitant interventions and treatment
fidelity often not reported.
TEACCH31
Insufficient
• 1 poor-quality cohort study; desirability of living situation and use of programming
rated more highly for TEACCH than other conditions; group homes rated more
desirable than institutions.
• Nonrandom assignment to groups; systematic diagnostic approach not reported
within study; inclusion/exclusion criteria not clearly stated; interventions not fully
described; assessors not masked.
Vocational
On-the-job
supports/supported
employment8, 35-39
Insufficient
• 5 poor-quality studies.
• Individual studies of different on-the job supports (broadly defined as services to
promote job placement and job retention) reported increased rates of employment
in the community relative to those without on-the-job supports. Because the
individual studies have not been replicated and are of poor quality, the strength of
evidence for the effect seen is insufficient, as more research is needed to quantify
the degree to which these interventions are likely to have an effect.
• Nonrandom assignment to groups in 3 studies, no comparison group in 2 case
series; attrition not always reported and interventions not always fully described;
treatment fidelity and differences in concomitant interventions frequently not
reported; assessors not masked.
Table B. Summary of strength of evidence and key outcomes of studies (continued)
Intervention
Strength
of
Evidence
Summary/Conclusions/Comments
Medical
Antipsychotics20, 21,
40
Insufficient
2 fair-quality RCTs and 1 poor quality crossover study.
Improvements in aggression, irritability/agitation, repetitive behavior, sensory motor
behaviors, and overall behavioral symptoms in participants receiving risperidone.
Treatment adherence not reported in 2 studies; assessors not masked and
participants not clearly characterized in 1 study.
Opioid receptor
antagonists19
Insufficient
1 poor-quality crossover study.
Significant increase in stereotypy in treated participants.
Participants not clearly characterized; adherence and differences in concomitant
interventions not reported.
Serotonin reuptake
inhibitors18, 20, 41-43
Insufficient
2 fair-quality RCTs, 3 poor quality case series.
Studies had inconsistent results: RCT of fluvoxamine reported decreases in
repetitive behavior, aggression, autistic symptoms, and language usage. Case
series addressing sertraline, fluoxetine, and clomipramine reported some benefits,
while a crossover study of clomipramine vs. placebo reported no significant
differences in autistic symptoms between groups.
Lack of comparison groups in 3 studies; treatment adherence not reported;
assessors not masked in some studies.
Allied Health
Facilitated
communication45, 46
Insufficient
2 poor-quality case series.
Facilitated communication did not increase participants’ communication or literacy
abilities over their independent abilities.
No comparison groups; differences in concomitant interventions not reported;
assessors not masked.
Music therapy47, 48
Insufficient
2 poor-quality case series.
Some gains in social skills reported using unvalidated and largely subjective
measures.
No comparison groups or measures of treatment fidelity; participants not clearly
characterized; assessors not masked; differences in concomitant interventions not
reported.
Leisure/recreation
program22
Insufficient
1 fair-quality RCT.
Positive effects on stress and quality of life in leisure group participants compared
with controls.
Attrition and treatment fidelity not reported; randomization method not clearly
described; differences in concomitant interventions not reported.
RCT = randomized controlled trial; TEACCH = Treatment and Education of Autistic and Communication related Handicapped
Children
In the behavioral literature research, social skills interventions utilizing individual/group 23, 24,
27, 28 and computer-based interventions 17, 25 suggested improvements across a variety of
caregiver-reported social skills and emotion recognition capacities respectively. However, each
study employed a different approach and paradigm, making comparison across interventions
impossible. Likewise, such social skills interventions have yet to demonstrate consistent
generalization of skills across settings and often limit interventions to individuals with average to
above average verbal and/or cognitive abilities.
Only a single poor-quality case series examined the effects of a more intensive,
comprehensive intervention approach. This study suggested improvement in adaptive skills and
high levels of family satisfaction with services for 34 adolescents receiving treatment in a
residential treatment setting over the course of 2 years. Given the lack of adequate comparison
group in this setting, there is very little information surrounding the impact of comprehensive
behavioral intervention approaches for this population.
Research into educational approaches for adolescents and young adults with ASD is very
limited, with only two small crossover studies identified in this population. These studies29, 30
focused on the impact of highly specified educational strategies and outcomes (e.g., vocabulary
development) and ultimately provide little evidence to support selection of either specific or
various broad-based educational strategies.
Studies of adaptive/life skills-focused interventions meeting our criteria were of poor quality,
addressed disparate interventions, and typically included few participants. Individual studies
documented specified short-term gains in learning or successfully executing an adaptive or life
skills-focused tasks, but the applicability and generalization of these findings is limited by the
highly specified approaches utilized.31-34 Additionally, studies were typically uncontrolled and of
short duration.
Among five studies of supported employment/vocational interventions,8, 35-39 all focused on
on-the-job supports as the employment/vocational intervention. No other vocational
interventions were reported in the literature meeting our study criteria. Our ability to know the
ultimate benefit of supported employment programs is limited given the existing research. No
study utilized random assignment, making it difficult to draw conclusions about the effectiveness
of the programs, and all studies were poor quality. Three small studies focused on employment
as an outcome of interest reported that supported employment interventions increased rates of
employment for young adults with ASD.8, 36, 39 Additional studies reported that supported
employment was associated with improvements in quality of life and core symptoms37, 38 and
cognitive functioning35 in supported employment participants relative to young adults with ASD
in sheltered work settings.
Supported employment interventions remain understudied. For example, only one study
examined rates of employment for programs that lasted 3 years or longer.8 Further, this longer
term study did not include a control group, making it impossible to determine the rates of
employment over time for young adults with ASD who were not participating in the supported
employment intervention. Finally, none of the studies examined whether increased employment
rates or improvements in other outcomes were sustained after the termination of the supported
employment intervention.
The use of medical interventions in adolescents and young adults with ASD is common.49
However, there is little evidence that supports the use of medical interventions specifically in this
population. Overall, most studies focused on the use of medications to address specific
challenging behaviors (i.e., aggression or irritability). Four studies were fair quality,18-21 and four
were poor.40-43The most consistent findings were identified for antipsychotic medications. A fair
quality RCT studying risperidone found improvements in aggression, repetitive behavior,
sensory motor behaviors, and overall behavioral symptoms.21 A crossover study of risperidone
also showed a significant reduction of irritability/agitation ratings with risperidone treatment, but
the control was indirect.40 A placebo-controlled crossover study found that haloperidol
significantly improved hyperactivity/defiance ratings, but no significant difference was found for
irritability/agitation or other symptoms.20 While limited literature supports the use of risperidone
in adolescents or young adults with ASD, the efficacy of risperidone in studies including mostly
children has moderate strength of evidence50 that is consistent with the results of the one fair
RCT and one poor crossover study in adults with ASD. There is therefore no evidence to suggest
that the effects of risperidone for irritability/agitation in ASD are specific to a particular age
range.
A number of studies of SRIs were identified but with limited consistency across studies as a
whole. An RCT of fluvoxamine showed decreases in repetitive behavior, aggression, autistic
symptoms, and language usage.18 In contrast, no significant differences were observed in a
crossover study of clomipramine versus placebo.20 Three case series of SRIs were also identified,
including sertraline, fluoxetine, and clomipramine, with each study reporting some benefit to
treatment.41-43 A recent study not meeting criteria for this review contributes to the limited data
on SRIs: the placebo-controlled RCT51 of fluoxetine included 37 individuals with ASD with a
mean age of 34.31 and reported improvements in repetitive behavior and ASD symptoms in the
treatment group and mild harms. This study used a different medication than the one fair quality
study in our age range, so it would be unlikely to influence the strength of evidence for a specific
medication. It is possible, however, that a systematic review of SRIs in the broader age range of
adults with ASD could provide data that might increase our confidence in the effect.
A crossover study of the opioid receptor antagonist naltrexone found no significant
improvements in problem behavior and showed worsening of stereotyped behavior with
naltrexone treatment compared with placebo.19
Based upon the published studies in adolescents and adults with ASD, the strength of
evidence is insufficient for harms associated with medications tested in this population. As in the
case of efficacy, the data on adverse effects associated with risperidone, including sedation and
weight gain, are consistent with the high strength of evidence for these adverse effects in
children with ASD.50 The available evidence therefore appears consistent in supporting our
understanding of the risk of these adverse events in ASD without being limited to a specific age
range. Of course, this does not mean that other medications tested in ASD are free of adverse
effects. It is reasonable to expect that, in contrast to efficacy, which is more likely to be specific
to disorder and symptom, adverse effects are more likely to extend across diverse groups of
subjects studied. Clinicians evaluating the evidence and sharing information with families
routinely take this perspective, as does the Food and Drug Administration in mandating that all
adverse events be listed for a drug, rather than just those for a particular indication.
Few studies of allied health interventions met our criteria.45-47 One fair quality RCT assessed
a 12-month recreation program22and reported improved quality of life and lower stress scores in
individuals participating in the leisure/recreation program compared with those on a waiting list.
Two studies of facilitated communication used approaches designed to assess the effects of
facilitation both with and without facilitators’ awareness of the word being prompted. Both
studies demonstrated some facilitator influence without specific effects on participants’
independent ability to communicate. One retrospective study of a music therapy program
reported some positive effects on participants’ socials skills using largely subjective outcome
measures.47 One poor-quality case series48 included 22 young adults engaged in a music therapy
intervention. Nearly all participants reported making friends during the program and were
generally satisfied with the program. Both studies assessed outcomes shortly after treatment, so
longer term effects of the interventions are not known.
Applicability of the Evidence
Study populations across interventions were highly variable. A number of studies included
individuals with ASD and significant intellectual disability or language impairment, while
studies assessing vocational and social skills-related behavioral interventions typically included
higher functioning individuals. Studies of medical interventions were all conducted in academic
clinic settings, which may limit applicability to the general population. Thus there was
substantial variability and limited information on developmental, cognitive, and behavioral
characteristics of study populations.
Future Research
The period of development representing the transition from adolescence to early adulthood
presents numerous challenges for individuals with and without neurodevelopmental challenges.
These challenges are compounded for individuals with ASD as they are presented with
additional complexities requiring efforts to maximize the possibility of a positive transition and
achievement of individual goals for independence. Despite increasing numbers of adolescents
facing the transition from adolescence to adulthood, intervention research lags behind. To date,
there is not sufficient strength of evidence for documenting the effects of any interventions in
this age group on specific outcomes.
Overall, there is a dearth of evidence in all areas of care for adolescents and young adults
with autism spectrum disorders and it is urgent that more rigorous studies be developed and
conducted. It is unlikely that large scale implementation of interventions will be considered until
a stronger evidence base is developed, despite growing numbers of individuals with need, and
some small studies demonstrating initial promise. A fruitful area for consideration may be
identifying programs/interventions that are appropriate candidates for developing treatment
manuals to encourage standardized replication of promising approaches.
Basic understanding of the effects of aging on health, cognitive skills, and other domains of
functioning is absent, and evaluations of interventions are rare. The lack of randomized,
controlled trials is notable in all categories of intervention, but especially so in medical
interventions, where substantial adverse events may be associated with medication use in
adolescence. Only three studies8, 31, 37, 38 (one reported in two publications) reported more than 12
months of followup; longer term data are needed in all areas of therapy. Furthermore, although
early intervention for individuals with ASD is often delivered in the home or at specialized
agencies, behavioral and educational interventions for adolescents and adults with ASD are
likely to take place in existing community-based settings such as schools and businesses, with
nonspecialists having a key role in implementation. Thus, another critical issue is to design
interventions for implementation in such settings.
The behavioral literature generally focuses on a subset of individuals with ASD, often those
who are higher functioning, and may not be representative of the range of individuals with
ASDs. In particular, more attention is warranted to understand the impact of behavioral
interventions in the lives of individuals and how these interventions generalize to real-world
impact and outcome.
Few studies addressing educational interventions in the adolescent and young adult
population have been conducted, and studies focusing on life skills or adaptive behaviors have
included few individuals, typically in short-term studies focused on highly specific short-term
intermediate outcomes. More research in both areas and over broader timeframes with more
clearly defined populations is critical for helping individuals with ASD transition to greater
independence.
In vocational research, studies are needed that illuminate which aspects of multifaceted
supported employment programs have the greatest impact. Studies that do show evidence of
effectiveness in this area should collect longer term data to describe the degree to which findings,
including the duration of employment, continue after the intervention itself is removed. These
studies should also broaden the outcomes measured, to include other functional outcomes such as
quality of life, educational attainment, residential outcomes, and social outcomes. Similarly,
allied health studies are needed to understand best approaches to fostering independent living
skills and ways in which improvements in motor skills may affect communication and other
domains.
Medical studies conducted in adolescents and young adults have focused largely on problem
behaviors, and additional data are needed on medical comorbidities in adolescents with ASD.
Clear evidence from earlier studies of antipsychotics, which included mostly younger children,
supports the use of risperidone and aripiprazole in children with ASD.50 The only fair-quality
study of risperidone in adults is consistent with the findings in children, but the strength of
evidence based upon the adult literature alone is insufficient to draw firm conclusions.
Population studies may be helpful to empirically group ASD patients by age in a way that fosters
more effective studies of treatments. Understanding the age-appropriateness of potential medical
treatments as based on social, physiological, pharmacological, and functional characteristics of
the population would help to prioritize future research, including the ways in which medical
comorbidities arise or increase as children with ASD move into adolescence and adulthood.
Increased use of such standardized age groupings would facilitate comparisons of effectiveness
within medical intervention categories as well as with nonmedical therapies. One way to support
accomplishing this is by developing treatment networks with adequate numbers of patients of
varying ages to participate in research.
Thus far, medication research in adolescents and young adults with ASD has been limited to
compounds that are already approved for other indications. As targeted treatments for ASD
emerge, initial studies will need to study adult populations to establish safety before moving into
studies of adolescents and finally children. Study of compounds not yet on the market could be
facilitated with partnerships between the academic and pharmaceutical communities. It will be
critical to consider the appropriate outcome measures and settings in which to study medication
response in adults. The heterogeneity in settings for adults with ASD is a significant impediment
to assessing symptom response. Ideally, medications would be combined with an educational or
psychosocial intervention that would mirror the school and therapeutic settings in which children
with ASD show improvements in social, communication, or behavioral function. Without some
level of educational or social challenge, it may be quite difficult to assess medication response.
Across all intervention types, research is needed on which outcomes to use in future studies.
The Aberrant Behavior Checklist is the best outcome measure for behavioral symptoms in ASD
in terms of both validity and reliability, but it does not directly index anxiety, mood, social, or
communication function, nor does it capture broader outcomes such as quality of life. More
outcome measures are needed to allow assessment of a broader range of symptoms, particularly
in individuals who may be higher functioning. No studies provide adequate information on
longer term outcomes, and particularly on outcomes related to achieving goals for independence
and quality of life. To some degree, this reflects a lack of understanding and consensus about
optimal outcomes and how to measure them.
We know little about which outcome measures are most appropriate and valid for this
population specifically; nor do we have good, empirical evidence about which outcomes are
valued by individuals and their families. Furthermore, it is unclear which outcomes are most
likely to change as a result of the very different types of interventions assessed in this population.
Substantial, foundational research should be done to identify and validate outcome measures in
the adolescent and young adult population with ASD.
Research is also necessary to understand how individuals’ expression of ASD symptoms and
the severity of symptoms may affect treatment over the lifespan. Foundational research is
necessary to understand the goals of individuals with autism and their families as future research
studies are planned. Similarly, little research addressing the effects of family and caregiver
interactions and characteristics on the responses of individuals’ with ASD to interventions exists.
Finally, for all research in this area, we encourage greater transparency in reporting,
particularly as it relates to reporting of randomization approaches, characterization of study
participants, description of the intervention and measures of fidelity and adherence. These are all
necessary to correctly understand the potential impact of the interventions being reported.
Conclusions
Given the number of individuals affected by ASD, there is a dramatic lack of evidence on
best approaches to therapies for adolescents and young adults with these conditions. In
particular, families have little in the way of evidence-based approaches to support interventions
capable of optimizing the transition of teens with autism into adulthood. Most of the studies
identified were of poor quality; while the five fair-quality studies were primarily of medical
interventions. Behavioral, educational, and adaptive/life skills studies were typically small and
short term and suggested some improvements in social skills and functional behavior.
Individual studies also suggested that vocational programs may increase employment
success, but the studies were small. By the same token, few data address the effectiveness and
harms of medical or allied health interventions in the adolescent and young adult population.
Although the studies that have been conducted focused on the use of medications to address
specific challenging behaviors, the effectiveness in managing irritability and aggression in this
age group remains largely unknown and can at best be inferred from studies including mostly
younger children.
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7. Taylor JL, Seltzer MM. Changes in the
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8. Howlin P, Alcock J, Burkin C. An 8 year
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11. Croen LA, Najjar DV, Ray GT, et al. A
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12. Cimera RE, Cowan RJ. The costs of services
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13. Schall C, McDonough J. Autism spectrum
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14. Chou R, Aronson N, Atkins D, et al. AHRQ
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15. Warren Z, Veenstra-VanderWeele J, Stone
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17. Golan O, Baron-Cohen S. Systemizing
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18. McDougle CJ, Naylor ST, Cohen DJ, et al.
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19. Willemsen-Swinkels SH, Buitelaar JK,
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22. Garcia-Villamisar DA, Dattilo J. Effects of a
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24. Tse J, Strulovitch J, Tagalakis V, et al.
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26. Valenti M, Cerbo R, Masedu F, et al.
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27. Laugeson EA, Frankel F, Gantman A, et al.
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28. Verhoeven EW, Marijnissen N, Berger HJ,
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23. PMID: 21698498.
29. Elliott RO, Jr., Hall K, Soper HV. Analog
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30. O'Connor IM, Klein PD. Exploration of
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31. Van Bourgondien ME, Reichle NC,
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32. Gentry T, Wallace J, Kvarfordt C, et al.
Personal digital assistants as cognitive aids
for high school students with autism: results
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2010;32(2):101-7.
33. Nelson DL, Gergenti E, Hollander AC.
Extra prompts versus no extra prompts in
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Sep;10(3):311-21. PMID: 6927657.
34. Jewell JD, Grippi A, Hupp SDA, et al. The
effects of a rotating classroom schedule on
classroom crisis events in a school for
autism. N Am J Psychol. 2007;9(1):37-52.
35. Garcia-Villamisar D, Hughes C. Supported
employment improves cognitive
performance in adults with Autism. J
Intellect Disabil Res. 2007 Feb;51(Pt
2):142-50. PMID: 17217478.
36. Lawer L, Brusilovskiy E, Salzer MS, et al.
Use of vocational rehabilitative services
among adults with autism. J Autism Dev
Disord. 2009 Mar;39(3):487-94. PMID:
18810627.
37. García-Villamisar D, Wehman P, Navarro
MD. Changes in the quality of autistic
people's life that work in supported and
sheltered employment. A 5-year follow-up
study. J Vocat Rehabil. 2002;17(4):309-12.
38. García-Villamisar D, Ross D, Wehman P.
Clinical differential analysis of persons with
autism in a work setting: A follow-up study.
J Vocat Rehabil. 2000;14(3):183-5.
39. Mawhood L, Howlin P. The outcome of a
supported employment scheme for high-
functioning adults with autism or Asperger
syndrome. Autism. 1999 Sep;3(3):229-54.
40. Hellings JA, Zarcone JR, Reese RM, et al. A
crossover study of risperidone in children,
adolescents and adults with mental
retardation. J Autism Dev Disord. 2006
Apr;36(3):401-11. PMID: 16596465.
41. McDougle CJ, Brodkin ES, Naylor ST, et al.
Sertraline in adults with pervasive
developmental disorders: a prospective
open-label investigation. J Clin
Psychopharmacol. 1998 Feb;18(1):62-6.
PMID: 9472844.
42. Brodkin ES, McDougle CJ, Naylor ST, et al.
Clomipramine in adults with pervasive
developmental disorders: a prospective
open-label investigation. J Child Adolesc
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21. PMID: 9334896.
43. Cook EH, Rowlett R, Jaselskis C, et al.
Fluoxetine treatment of children and adults
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44. Miller AR, Zwaigenbaum L. New provincial
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45. Bebko JM, Perry A, Bryson S. Multiple
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1996 Feb;26(1):19-42. PMID: 8819769.
46. Eberlin M, McConnachie G, Ibel S, et al.
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47. Kaplan RS, Steele AL. An analysis of music
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48. Greher GR, Hillier A, Dougherty M, et al.
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49. Mandell DS, Morales KH, Marcus SC, et al.
Psychotropic medication use among
Medicaid-enrolled children with autism
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Mar;121(3):e441-8. PMID: 18310165.
50. McPheeters ML, Warren Z, Sathe N, et al. A
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Pediatrics. 2011 May;127(5):e1312-21.
PMID: 21464191.
51. Hollander E, Soorya L, Chaplin W, et al. A
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Introduction
Need for Evidence Regarding Treatment of Autism Spectrum
Disorders in Adolescents and Young Adults
Autism Spectrum Disorders (ASD) are among the most common neurodevelopmental
disorders, with an estimated prevalence of one in 110 children in the United States having an
ASD.1 They are typically diagnosed in early childhood, often at or before preschool age. The
diagnosis is fundamentally behaviorally based (i.e., there is no specific genetic test or clinical/
laboratory procedure for diagnosis) and rests on documented core impairments related to social
interaction, communication, as well as restricted and repetitive behavior. Diagnoses made by
clinical providers, often pediatricians or behavioral providers, are based on documented
symptom patterns in these domains.
Numerous screening and diagnostic tools are available to help document and measure
symptoms of autism, with research investigations increasingly utilizing such measures in
combination with clinical diagnoses in order to more accurately describe, measure, and analyze
the heterogeneity in presentation associated with ASD. In addition to impairments in core
symptom areas, many individuals with ASD also have impaired cognitive skills, atypical sensory
behaviors, or other complex medical and psychiatric symptoms and conditions, such as seizure
disorders, motor impairments, hyperactivity, anxiety, and self-injury/aggression.
More than 55,000 individuals between the ages of 15 and 17 in the United States likely have
an ASD.2 For some individuals, core symptoms of ASD (impairments in communication and
social interaction and restricted/repetitive behaviors and interests) may improve with intervention
and over time;3-5 however, deficits typically remain throughout the lifespan although
developmental expression may vary.6 As children transition to adolescence and young adulthood,
developmentally appropriate interventions to ameliorate core deficits may continue, but the focus
of treatment often shifts toward promoting adaptive behaviors that can facilitate and enhance
independent functioning.6 Treatments for some must take into account that new symptoms may
emerge with adolescence as well as engagement with new developmental challenges (e.g.,
independent living, vocational engagement, postsecondary education). In particular, families and
caregivers have to make choices regarding care that cross a broad spectrum of clinical,
behavioral and educational areas.
Current data suggest that attainment of independent living or employment in adulthood for
individuals with an ASD is variable, with factors that predict the ability to live and work
independently not well elucidated.6 Furthermore, the limited extant research on outcomes for
adolescents and young adults with ASD documents difficulties in achieving markers of
functional independence, including employment, for the vast majority of these individuals.7
Specifically, most adults with ASD live dependent lives that require considerable supports; fewer
than a third have regular employment; most live with their parents or in supported living; and
those who are employed are often in jobs that pay below a living wage.8-12 In part because of
these high levels of dependence, most individuals with ASD will require some sort of supports or
intervention, often at intensive levels, throughout adolescence and adulthood.
The estimated costs of medical and non-medical care (e.g., special education, daycare) are
prodigiously high. One study estimates that the total yearly societal per capita cost of caring for
and treating a person with autism in the United States at $3.2 million and at about $35 billion for
an entire birth cohort of individuals with autism.13 A study of health care utilization in a large
group health plan revealed increased medication costs in older children with an ASD when
compared with younger children, as well as similarly aged adolescents without an ASD; other
care costs were also higher in this population, including a significantly increased rate of
hospitalizations.14
Costs of transitional and employment programs are also high for young adults with ASD. A
recent analysis of U.S. federal- and state-funded vocational rehabilitation programs showed that
enrolled individuals with ASD were among the most costly of nine disability groups examined,
with costs even higher among those with ASD and another comorbid disability. These data also
showed, however, that those with ASD had a higher rate of employment (40.8%) at the time of
case closure when compared with those with other disabilities, though with fewer work hours
and lower wages than some other disability groups.15
Although few studies have examined this stage of the lifespan specifically, one study
suggests that improvements in symptoms and problem behaviors observed while youth with
ASD were in high school slowed down or stopped after they left high school.16 Many individuals
lose access to school- and age-linked services, and many of the services available to adults
require waiting lists.16, 17 The lack of services available to help young adults with ASD transition
to greater independence has been noted by researchers for a number of years,18 and is
increasingly a topic in the lay media.19 To date, the specific programs and interventions that
underlie more positive functional, adaptive, social, and employment outcomes for individuals
with ASD during the transition to adulthood and beyond are poorly understood. Further, it is
unclear how such outcomes are best assessed in the face of the inherent heterogeneity and wide
scope of impairments associated with ASD.6, 20 This lack of information potently limits the
ability of individuals, families, practitioners and service systems to provide the appropriate care
to optimize quality of life and minimize the costs associated with ASD over the lifespan.
This review examines the effects of available interventions in adolescents and young adults
with ASD, focusing on the following outcomes: core symptoms of ASD; medical and mental
health comorbidities; functional behaviors and independence; the transition to adulthood, and
family outcomes.
Interventions Used To Treat ASD
The expression and severity of symptoms of ASD differs widely across individuals and over
time. Treatments may include a range of behavioral, psychosocial, educational, medical, and
complementary approaches as well as those focused on transitional process and improving
outcomes for parents/families of individuals with ASD.
The following sections briefly describe interventions discussed in the literature meeting our
criteria for this review. Additional interventions for adolescents and young adults with ASD that
did not meet criteria for our review are described in recent systematic and narrative reviews.21-27
Behavioral Interventions
Studies of behavioral interventions available for this review are presented in the broad
subcategories of social skills interventions and intensive behavioral interventions.
Social Skills Interventions
Difficulty with reciprocal social interaction is considered one of the core impairments of
ASD. The social impairment seen in ASD takes many forms and can vary greatly from one
individual to the next. For adolescents and young adults, social skills interventions often focus on
enhancing individuals’ interactions with peers and other adults by teaching skills necessary for
fluid interaction including instruction perspective-taking, social problem-solving, and
understanding social and emotional rules. Skill-based approaches have tried to address social
vulnerability through direct group instruction as well as interactive computer based instruction.
Intensive Behavioral Interventions
Comprehensive intensive behavioral interventions that focus simultaneously on multiple
target areas are quite common for preschool children with ASD (e.g., University of California,
Los Angeles/Lovaas model and early intensive behavioral intervention variants, Early Start
Denver model, parent training paradigms). Studies that use behavioral approaches in an intensive
and comprehensive fashion are uncommon during adolescence and young adulthood, although
some programs for older individuals with ASD (not included in this review) may use elements of
comprehensive approaches.
Educational Interventions
Most children and adolescents with ASD receive a substantial amount of their treatment in an
educational or center-based setting, often beginning early in life (e.g., preschool age).
Educational interventions often aim at enhancing specific areas of academic functioning (e.g.,
reading skills), but also quite frequently attempt to address social, cognitive, and behavioral
challenges within an educational setting. In addition to these targets, psychoeducational
interventions are also often provided in an attempt to prevent or ameliorate specific areas of
behavioral concern (i.e., sleep issues, puberty/sexuality related concerns) and provide family
support.
Vocational Interventions
Given the core and associated impairments related to ASD, many young adults exhibit
challenges finding and sustaining involvement in appropriate and meaningful vocational
activities. A number of interventions related to vocational attainment have focused on
developing supportive mechanisms to secure employment. Such approaches often involve an
interventionist, such as a job coach, and explicit instruction in the skills necessary to accomplish
specific occupational functions. In addition, some approaches have attempted to incorporate
instruction in the social and other skills necessary to identify and realize potential employment
opportunities (e.g., interviewing).
Adaptive/Life Skills Interventions
While comprehensive behavioral interventions for adolescents and young adults are
uncommon, many interventions use applied behavior analysis-based intervention to target and
improve important areas of daily functional impairment. These skills, often called adaptive or
life skills, vary by specific targets (e.g., feeding, dressing) or more complex tasks (e.g., teaching
a sequence of behavior). These interventions may also target reducing challenging behaviors
(e.g., self-injury, self-stimulatory behavior, aggression) that interfere with day to day skills and
functioning.
Medical and Related Interventions
Medical interventions for symptoms of ASD include pharmacological agents, therapeutic
diets, hormonal supplements, hyperbaric oxygen, chelating agents, and many other therapies.
Risperidone (age 5 to 16 years) and aripiprazole (age 6 to 17 years), both atypical antipsychotic
medications, are the only medical interventions that have U.S. Food and Drug Administration
approval for patients with autistic disorder. Other core and related symptoms are treated with
medications that are used in an “off-label” fashion. Antipsychotic medications act on the
dopamine system and other neurotransmitter systems, such as serotonin.28-31 Antipsychotic
medications are generally divided into typical antipsychotics, which are older and primarily have
affinity for dopamine D2 receptors, and atypical antipsychotics which are newer and show a
more diverse receptor profile. Typical antipsychotics studied in ASD include medications like
haloperidol. Atypical antipsychotic medications include risperidone and aripiprazole, which are
approved to treat irritability in children with autism, and have moderate and high evidence of
efficacy based upon an earlier systematic review in children with ASD.32
Serotonin reuptake inhibitors (SRIs) are effective in treating anxiety, depression, and
obsessive-compulsive disorder. There is overlap between the repetitive behaviors of ASD and
obsessive compulsive disorder.33, 34 Additionally, high blood levels of serotonin are a biomarker
seen in 25 to 30 percent of children with autism, pointing to the serotonin system as a potential
target for treatment.35, 36 Randomized controlled trials and open-label trials with serotonin
reuptake inhibitors in children with ASD have shown some promise but considerable variability
in treating repetitive behaviors, anxiety, and aggression.32, 37 SRIs include tricyclic
antidepressants and more selective inhibitors. The newer class of SRIs, selective serotonin
reuptake inhibitors, includes fluvoxamine, sertraline, and fluoxetine.
Opioid antagonists have been used in patients with ASD based upon the hypothesis that the
opioid system may be involved in maintaining or reinforcing self-injurious behaviors.38
Naltrexone is one opiate antagonist that has been investigated for treatment of self-injury,
hyperactivity, or stereotyped movements in children with autism; although without evidence
from randomized controlled trials favoring its use.39-41
Allied Health Interventions
Several allied health interventions address core symptoms of ASD as well as associated
difficulties and deficits. Social communication vulnerabilities are considered core features of
ASD. As such, language difficulties and nonverbal communication challenges are often
important targets of treatment. Historically, one communication intervention, facilitated
communication, focused on helping individuals with communication and language challenges
communicate via an interventionist or facilitator. More recently, interventions have utilized
technology and augmentative communication therapies/devices in improving communication
skills in individuals with ASD.
Other approaches have focused on teaching specific aspects of speech and language
development (i.e., production, pragmatic language interventions). A number of additional
interventions include occupational therapy techniques, movement and music therapies, as well as
approaches aimed at sensory integration or addressing challenging sensory behaviors.
Importance of this Review
Current data suggest that attainment of independent living or employment in adulthood for
individuals with an ASD is variable, with factors that predict the ability to live and work
independently not well elucidated.6 Available data suggest that individuals with ASD will
require some sort of intervention throughout adolescence and adulthood, and the estimated costs
of medical and non-medical (e.g., special education, daycare) care are prodigiously high.27 One
study estimates that the total yearly societal per capita cost of caring for and treating a person
with autism in the United States at $3.2 million and at about $35 billion for an entire birth cohort
of individuals with autism.13 A study of healthcare utilization in a large group health plan
revealed increased medication costs in older children with ASD as compared with younger
children as well as similarly-aged adolescents without ASD; other care costs were also higher in
this population, and the rate of hospitalizations was significantly increased.14
Costs of transitional and employment programs are also high for young adults with ASD. A
recent analysis of U.S. federal and state-funded vocational rehabilitation programs showed that
the prevalence of ASD among those in training programs increased from 0.2 percent to 0.6
percent from 2002 to 2006; those with ASD were among the most costly of nine disability
groups examined, with costs even higher among those with ASD and another comorbid
disability. These data also showed, however, that those with ASD had a higher rate of
employment (40.8%) at the time of case closure as compared with those with other disabilities,
though with fewer work hours and lower wages than some other disability groups.15
There is no cure for ASD and no global consensus regarding which intervention strategies are
most effective. Chronic management, often using multiple treatment approaches, may be
required to maximize ultimate functional independence and quality of life by minimizing the
core ASD features, facilitating development and learning, promoting socialization, reducing
maladaptive behaviors, and educating and supporting families. Investigators in the area have
noted that less research on therapies for adolescents or young adults exists than for younger
children,42 and such research is increasingly critical as the prevalence of ASD continues to grow
and as children with ASD diagnoses reach adolescence.
Scope and Key Questions
Scope of This Report
We focused this review on interventions for adolescents and young adults between the ages
of 13 and 30 with ASD (Autistic Disorder, Asperger syndrome, pervasive developmental
disorder-not otherwise specified) and addressed questions related to the effectiveness of
therapies targeting core symptoms of ASD (impairments in communication, social interaction,
and behavior); aimed at common medical or mental health comorbidities, which include
associated symptoms such as irritability; addressing the process of transitioning to adulthood;
and addressing family outcomes.
Key Questions
We have synthesized evidence in the published literature to address these Key Questions:
Key Question 1: Among adolescents and young adults with ASD, what are the effects of
available interventions on the core symptoms of ASD?
Key Question 2: Among adolescents and young adults with ASD, what are the effects of
available interventions on common medical and mental health comorbidities (e.g., epilepsy,
sleep disorders, motor impairments, obesity, depression, anxiety, acute and episodic aggression,
attention deficit hyperactivity disorder, etc.)?
Key Question 3: Among adolescents and young adults with ASD, what are the effects of
available interventions on functional behavior, attainment of goals toward independence,
educational attainment, occupational/vocational attainment, life satisfaction, access to health and
other services, legal outcomes, and social outcomes?
Key Question 4: Among adolescents and young adults with ASD, what is the effectiveness
of interventions designed to support the transitioning process, specifically to affect attainment of
goals toward independence, educational attainment, occupational/vocational attainment, life
satisfaction, access to health and other services, legal outcomes, and social outcomes?
Key Question 5: Among adolescents and young adults with ASD, what harms are associated
with available interventions? Harms are defined by the Effective Health Care Program as all
possible adverse consequences of an intervention, including adverse events.
Key Question 6: What are the effects of interventions on family outcomes?
Organization of This Evidence Report
The Methods section describes our processes including our search strategy, inclusion and
exclusion criteria, approach to review of abstracts and full publications, and our method for
extraction of data into evidence tables and compiling evidence. We also describe our approach to
grading of the quality of the literature and to evaluating the strength of the body of evidence.
The Results section presents the findings of the evidence report, synthesizing them by
category of intervention, Key Question, and outcomes reported. We report the number and type
of studies identified, and we differentiate between total numbers of publications and unique
studies. The final section of the report discusses key findings and expands on methodologic
considerations relevant to each Key Question. We also outline the current state of the literature
and challenges for future research in ASD in the target age range.
The report includes a number of appendixes to provide further detail on our methods and the
studies assessed. The appendixes are as follows—
• Appendix A. Exact Search Strings and Results
• Appendix B. Categorization of Study Designs
• Appendix C. Sample Data Extraction Forms
• Appendix D. Evidence Tables
• Appendix E. Quality Assessment Form
• Appendix F. Excluded Studies
• Appendix G. Quality of the Literature
We also include a list of abbreviations and acronyms at the end of the report.
Uses of This Report
This evidence report addresses the Key Questions outlined previously using methods
described in the report to conduct a systematic review of published literature. We anticipate that
the report will be of value to clinicians who treat individuals with ASD, including pediatricians,
psychologists, psychiatrists, allied health professionals, and other clinicians who provide care for
ASD. The report itself is not a guideline. It is a review of evidence that other groups and
individuals can use in developing guidelines or treatment decisions, but we assume that those
decisions would be made with other considerations as well, including an individual’s diagnosis,
severity of ASD symptoms, concomitant conditions, and ability to transition to more independent
functioning.
In addition, this review will be of use to the National Institutes of Health, Centers for
Medicare & Medicaid Services, and the Health Resources and Services Administration–all of
which have offices or bureaus devoted to developmental issues. This report can bring
practitioners up to date about the current state of evidence, and it provides an assessment of the
quality of studies that aim to determine the outcomes of therapeutic options for the management
of ASD. It will be of interest to individuals affected by ASD and their families because of the
high prevalence of ASD, significant personal costs associated with it, and the recurring need for
individuals with ASD, their families, and their health care providers to make the best possible
decisions among numerous options.
Researchers can obtain a concise analysis of the current state of knowledge in this field. They
will be poised to pursue further investigations that are needed to understand best approaches to
therapies for adolescents and young adults with ASD.
Methods
Topic Development and Refinement
The topic for this report was nominated by Autism Speaks in a public process. We drafted
the initial Key Questions and analytic framework and refined them with input from key
informants and a focus group of family members of adolescents and young adults with autism
spectrum disorders (ASD). After review from the Agency for Healthcare Research and Quality
(AHRQ), the questions and framework were posted to a public Web site. The public was invited
to comment on these questions.
After reviewing the public commentary, we drafted final Key Questions and submitted them
to AHRQ for review. We identified technical experts on the topic of ASD in adolescents and
young adults to provide assistance during the project. Technical Expert Panel (TEP) members
represented the clinical and research communities from a range of perspectives. They were
invited to participate based on our commitment to engaging a range of experts who could help
solidify the decisional dilemmas facing individuals and families with ASD. They included both
researchers and clinicians with expertise in behavioral, medical, social, psychological and
educational issues. The TEP contributed to AHRQ’s broader goals of (1) creating and
maintaining science partnerships as well as public-private partnerships and (2) meeting the needs
of an array of potential customers and users of its products. Thus, the TEP was both an additional
resource and a sounding board during the project. The TEP included six members serving as
technical or clinical experts. To ensure robust, scientifically relevant work, we called on the TEP
to provide reactions to work in progress. TEP members participated in conference calls and
discussions through e-mail to:
• Refine the analytic framework and Key Questions at the beginning of the project;
• Discuss the preliminary assessment of the literature, including inclusion/exclusion
criteria;
• Provide input on assessing the quality of the literature.
Role of the AHRQ Task Order Officer
The Task Order Officer (TOO) was responsible for overseeing all aspects of this project. The
TOO helped to develop a common understanding among all parties involved in the project,
resolved questions and ambiguities, and addressed our queries regarding the scope and processes
of the project. The TOO reviewed the report for consistency, clarity, and to ensure that it
conforms to AHRQ standards.
Analytic Framework
The analytic framework (Figure 1) summarizes the process by which individuals with ASD
and their families/caregivers make and modify treatment choices. Treatment choices include
surgical or nonsurgical approaches and may lead to intermediate outcomes including changes in
communication skills, academic skill development, or social skills. Interventions may also lead
to long-term outcomes such as adaptive independence and changes in psychosocial well-being.
Interventions may also lead to changes in family outcomes such as parent distress and may be
associated with harms/adverse effects. Numbers in circles within the diagram indicate the
placement of Key Questions in relation to the treatment process.
The analytic framework summarizes the process by which individuals with autism spectrum disorders (ASD) and their families/caregivers make and modify treatment choices. Treatment choices may target intermediate outcomes including changes in communication skills, academic skill development, or social skills. Interventions lead to long-term outcomes such as adaptive independence and changes in psychosocial well-being. Family outcomes such as parent distress may also be targeted by interventions and may lead in turn to long-term outcomes. Finally, interventions may be associated with harms/adverse effects. Numbers in circles within the diagram indicate the placement of Key Questions in relation to the treatment process.
Figure 1. Analytic framework for interventions for adolescents and young adults with ASD
KQ = Key Question
Literature Search Strategy
Databases
A librarian employed search strategies provided in Appendix A to retrieve research on
therapies for adolescents and young adults with ASD. Our primary literature search employed 4
databases: MEDLINE® via the PubMed interface, PsycINFO® (psychology and psychiatry
literature), the Educational Resources Information Clearinghouse, and the Cumulative Index of
Nursing and Allied Health Literature database. Our search strategies used a combination of
subject heading terms appropriate for each database and key words relevant to ASD (e.g., autism,
Asperger). We limited searches to the English language and literature published since 1980 and
the publication of standardized diagnostic criteria for ASD (i.e., Diagnostic and Statistical
Manual of Mental Disorders III).
We also manually searched the reference lists of included studies and of recent narrative and
systematic reviews and meta-analyses addressing ASD. We also invited TEP members to
provide additional citations.
Regulatory Information
The AHRQ Scientific Resource Center also searched for information on the following
specific medications and interventions used to treat ASD. We requested regulatory information
on these drugs and devices as they are either approved by the U.S. Food and Drug
Administration to treat irritability in ASD or are beginning to be used in the ASD population and
have not yet been well-reported in the published literature (i.e., hyperbaric oxygen):
• Risperidone
• Aripiprazole
• Hyperbaric oxygen chambers.
The Scientific Resource Center sought information in resources including the websites of
the Food and Drug Administration and Health Canada and clinical trials registries such as
ClinicalTrials.gov. We also gave manufacturers of these medications and devices an opportunity
to provide additional information, though none did so.
Search Terms
Controlled vocabulary terms served as the foundation of our search in each database (e.g.,
MEDLINE vocabulary terms including autistic disorder, child development disorders,
pervasive), complemented by additional keyword phrases (e.g., Asperger, autism). We also
limited searches to items published in English and from 1980 to the present. Our searches were
executed between September 2010 and December 2011. Appendix A provides our search terms
and the yield from each database. We imported all citations into an electronic database.
Process for Study Selection
Inclusion and Exclusion Criteria
We developed criteria for inclusion and exclusion based on the patient populations,
interventions, outcome measures, and types of evidence specified in the Key Questions and in
consultation with the TEP. Table 1 summarizes criteria.
Table 1. Inclusion and exclusion criteria
Category
Criteria
Study population
Adolescents or young adults (ages 13-30) with ASD (autistic disorder, Asperger
syndrome, PDD-NOS) or families/caregivers of individuals with ASD between
the ages of 13-30
Interventions
Interventions aimed at ameliorating core symptoms of ASD, affecting
independent functioning, adaptive behavior, or the transition process, or
targeting family outcomes
Comparators
Placebo
Other intervention
Outcomes
Social skills/interaction, language and communication, repetitive and other
maladaptive behaviors, motor outcomes, psychological distress, adaptive skills
development, academic skills development, and family outcomes including
family distress and family satisfaction
Time period
Studies published from 1980–present with no limits on timing of outcomes
Setting
Any setting including educational, residential, and clinic
Publication languages
English only
Admissible evidence (study design
and other criteria)
Admissible designs
• Controlled trials, observational studies including prospective and
retrospective cohort studies, prospective and retrospective case series
Study size
• N = 20 total individuals between 13-30 years of age with ASD or family
members of such individuals
Other criteria
• Original research studies that provide sufficient detail regarding
methods and results to enable use and adjustment of the data and
results
• Patient populations must include adolescents or young adults (13-30
years of age) with ASD or families/caregivers of individuals with ASD
between the ages of 13-30
• Studies must address one or more of the following:
o Treatment modality aimed at modifying ASD core symptoms,
common comorbidities, family-related outcomes, or assisting
with transitional issues
o Outcomes (including harms) related to interventions for ASD
• Studies must include extractable data on relevant outcomes, including
data presented in text or tables (vs. solely in figures)
• Studies must present aggregate data (vs. only data for each individual
participant)
ASD = autism spectrum disorders; N = number; PDD-NOS = pervasive developmental disorder-not otherwise specified
Study Population
Studies needed to provide adequate information to ensure that participants fell within the
target age range of age 13 to 30. We selected the lower bound of 13 as a previous AHRQ
comparative effectiveness review of therapies for children with ASD included studies with
individuals = age 12.43 As this review is focused in part on individuals in the period of
transitioning to more independent functioning, we used the upper bound of 30 as individuals
with ASD can remain in the secondary school system until age 21. Thus some individuals may
not experience the transition to more independent functioning in their twenties as would be
expected for typically developing individuals. The upper age of 30 accounted for potential
developmental delays in individuals with ASD.
For studies with populations including individuals with ASD either under the age of 13 or
over age 30, we retained the study if we could infer that at least 50 percent of the study
participants were in the 13 to 30 age range or if the mean age of participants was in the 13 to30
age range. Similarly, for studies including individuals with ASD and those with other
developmental disabilities we retained the study if we could isolate data on those participants
with ASD.
We note that if a research study used a comparison group that did not contribute to an
estimate of the contrast of interest in our review, we included the one arm of the study that was
relevant. For example, an intervention study in which the intervention group is individuals with
ASD and the comparison group is a group of individuals with Down Syndrome would not
provide an estimate of the effect of the intervention for children with ASD. Rather than exclude
this study, we include the group of individuals with ASD as a case series.
Sample Size
We excluded studies that included fewer than 20 total participants in the target age range
with ASD or family members of such individuals. Our goal was to identify and review the best
evidence for assessing the efficacy and effectiveness of therapies for adolescents and young
adults with ASD, with an eye toward utility in the treatment setting. Interventions to address
ASDs are frequently behavioral in nature and highly intensive. They are also frequently adapted
to be targeted to specific study participants given the significant heterogeneity of individuals
with ASD. In part because this makes behavioral research quite complex and intensive, study
sizes tend to be very small. A cutoff sample size of 20 provides a balance, allowing us to review
and comment on adequate literature for the review but with studies large enough to suggest
effects of the interventions.
With the assistance of our technical experts, we selected a minimum sample size of 20 in
order to maximize our ability to describe the state of the current literature, while balancing the
need to identify studies that could be used to assess treatment effectiveness.
Study Design
We accepted any study designs except individual case reports. Our approach to categorizing
study designs is presented in Appendix B.
Outcomes
We assessed outcomes in the broad areas of social skills/interaction, language and
communication, repetitive and other maladaptive behaviors, motor outcomes, psychological
distress, adaptive skills development, academic skills development, and family outcomes
including family distress and family satisfaction related to interventions. We considered
intermediate outcomes as those that occur directly as a result of the intervention and that may
also have longer term implications for the ultimate, functional outcomes that are the long-term
goal of therapies. We also considered changes in long-term functional outcome areas, including
adaptive independence/self care, academic/occupational/vocational engagement and attainment,
psychological well-being, psychosocial adaptation, residential outcomes, legal outcomes,
social/relationship-focused outcomes (interpersonal relationships, community
involvement/societal participation, self-actualization and acceptance, etc.), access to health
services (conservatorship, access to day care, access to health care, access to social, financial,
and other support systems), and use of public programs.
We also assessed the harms of interventions, defined by the AHRQ Effective Health Care
program as the totality of adverse consequences of an intervention.44 Harms may include—
• Adverse behavioral or psychosocial reactions to behavioral or other therapies (e.g.,
increased aggression or anxiety)
• Regression of language, skills, or behaviors
• Increases in or worsening of comorbid symptoms
• Adverse reactions to drug therapies (e.g., somnolence, weight gain)
• Reduction in and negative influences on quality of life.
Language
We focused the review on studies published in English. In the opinion of our content experts,
most research on ASD is published in English regardless of the native language of the
investigators or country of publication.
Screening of Studies
Once we identified articles through the electronic database searches, review articles, and
bibliographies, we examined abstracts of articles to determine whether studies met our criteria.
Two reviewers separately evaluated each abstract for inclusion or exclusion, using an Abstract
Review Form (Appendix C). If one reviewer concluded that the article could be eligible for the
review based on the abstract, we retained it for full text assessment.
Two reviewers independently assessed the full text of each included study using a
standardized form (Appendix C) that included questions stemming from our inclusion/exclusion
criteria. Disagreements between reviewers were resolved by a third-party adjudicator. The group
of abstract and full text reviewers included expert clinicians and researchers and health services
researchers.
Categorization of Interventions
Interventions to treat ASD overlap substantially21 and cleanly identifying the category into
which an intervention should be placed is difficult. We adapted the categorization approach we
used in our previous review of therapies for children with ASD,43 and studies fell into the
following categories:
• Behavioral interventions. We defined behavioral interventions to include intensive
behavioral and developmental interventions and social skills interventions employing
either peer group- or computer-based approaches.
• Educational interventions. Educational interventions are those focusing on improving
educational and cognitive skills and intended primarily to be administered in educational
settings, or studies for which the educational arm was most clearly categorized.
• Adaptive/life skills-focused interventions. We considered those interventions focused
on developing skills to assist with independent functioning and independent execution of
activities of daily living as falling within this category. Interventions described in this
review include interventions targeting transitioning to a new school routine, self-care, and
cognitive aids.
• Vocational interventions. We classified interventions targeting job skills, employment
supports, or placing individuals into work as vocational interventions. Such interventions
included in the literature meeting our criteria for this review comprise sheltered
workshops, supported employment, and vocational rehabilitation.
• Medical and related interventions. We broadly defined medical and related
interventions as those that included the administration of external substances to the body
in order to treat symptoms of ASD; medical interventions represented in the literature
included in this review comprised prescription medications.
• Allied health interventions. Allied health interventions included therapies that may be
provided by occupational and physical therapists, including recreational therapies and
promoting engagement in physical activity. We also considered therapies such as
facilitated communication and music therapy as allied health interventions.
Data Extraction and Data Management
The staff members and clinical experts who conducted this review jointly developed the
evidence tables, which were used to extract data from the studies. We designed the tables to
provide sufficient information to enable readers to understand the studies, including issues of
study design, descriptions of the study populations (for applicability), description of the
intervention, and baseline and outcome data on constructs of interest.
The team abstracted several articles into the evidence table and then reconvened as a group to
discuss the utility of the table design. We repeated this process through several iterations until we
decided that the table included the appropriate categories for gathering the information contained
in the articles. All team members shared the task of initially entering information into the
evidence table. Another member of the team also independently reviewed the articles and edited
all initial table entries for accuracy, completeness, and consistency. The full research team met
regularly during the article extraction period and discussed issues related to data extraction (e.g.,
optimal level of detail in the description of the intervention, what constituted assessment of
treatment fidelity). In addition to outcomes related to treatment effectiveness and family
outcomes, we extracted all data available on harms. Harms encompass the full range of specific
negative effects, including the narrower definition of adverse events.
The final evidence tables are presented in their entirety in Appendix D. Studies are presented
in the evidence tables alphabetically by the last name of the first author within each year. When
possible to identify, analyses resulting from the same study were grouped into a single evidence
table.
Individual Study Quality Assessment
We used a components approach to assessing the quality of individual studies, following
methods outlined in the AHRQ Effective Health Care program’s Methods Guide for
Effectiveness and Comparative Effectiveness Reviews.45 Decision rules regarding application of
the tools were developed a priori by the research team. In some instances, it was appropriate to
apply specific questions only to one body of literature (e.g., treatment fidelity to behavioral
studies and medication adherence to medical studies) and we note those cases where appropriate.
We assessed each domain individually and combined them for an overall quality level as
described below. Three levels were possible: good, fair, and poor (Table 2). Appendix E includes
the questions we used to assess each domain.
Table 2. Description of study quality levels
Quality Level
Description
Good
Good studies are considered to have the least bias and results are considered valid. A good study
has a clear description of the population, setting, interventions, and comparison groups; uses a valid
approach to allocate patients to treatments; has a low dropout rate; and uses appropriate means to
prevent bias; measure outcomes; analyze and report results.
Fair
Fair studies are susceptible to some bias, but probably not sufficient to invalidate the results. A
study may be missing information, making it difficult to assess limitations and potential problems. As
the “fair quality” category is broad, studies with this rating vary in their strengths and weaknesses.
The results of some fair-quality studies are possibly valid, while others are probably valid.
Poor
Poor studies are subject to significant bias that may invalidate the results. These studies have
serious errors in design, analysis, or reporting; have large amounts of missing information; or have
discrepancies in reporting. The results of a poor-quality study are at least as likely to reflect flaws in
the study design as to indicate true differences between the compared interventions.
Determining Quality Levels
We assessed each domain described above individually and considered the individual ratings
to determine an overall quality assessment of good, fair, or poor. We required that studies receive
positive scores on all questions to receive a rating of good quality. We required that studies
receive positive ratings on the following questions for a fair rating:
• Did the study employ a group design?
• Was there an appropriate comparison group?
• Was a systematic diagnostic approach used within the study?
• Were inclusion and exclusion criteria clearly stated?
• Was the intervention fully described?
• Did outcome measures demonstrate adequate reliability and validity?
• Were outcome data collected from sources appropriate to the target outcome?
• Was an appropriate statistical analysis used?
We rated studies without positive scores on these questions as poor quality and retained poor
quality studies as part of the evidence base.
Data Synthesis
There was significant heterogeneity among studies reporting therapeutic results of
interventions for adolescents and young adults with ASD, including heterogeneity of population
characteristics, heterogeneity of interventions, and heterogeneity of outcome measures.
Therefore, it was not appropriate to perform any meta-analysis.
Grading the Body of Evidence for Each Key Question
The assessment of the literature is done by considering both the observed effectiveness of
interventions and the confidence that we have in the stability of those effects in the face of future
research. The degree of confidence that the observed effect of an intervention is unlikely to
change is presented as strength of evidence, and it can be regarded as insufficient, low, moderate,
or high. Strength of evidence describes the adequacy of the current research, both in terms of
quantity and quality, as well as the degree to which the entire body of current research provides a
consistent and precise estimate of effect. Interventions that have demonstrated benefit in a small
number of studies but have not yet been replicated using the most rigorous study designs will
therefore have insufficient or low strength of evidence to describe the body of research. Future
research may find that the intervention is either effective or ineffective.
Methods for applying strength of evidence assessments are established in the AHRQ
Effective Health Care Program’s Methods Guide for Effectiveness and Comparative
Effectiveness Reviews46 and are based on consideration of four domains: risk of bias,
consistency in direction of the effect, directness in measuring intended outcomes, and precision
of effect (Table 3). Strength of evidence is assessed separately for major intervention-outcome
pairs.
Table 3. Domains used to assess strength of evidencea
Domain
Explanation
Risk of bias
Degree to which the included studies for a given outcome or comparison have a high
likelihood of adequate protection against bias (i.e., good internal validity), assessed
through two main elements:
• Study design (e.g., RCTs or observational studies)
• Aggregate quality of the studies under consideration.
Information for this determination comes from the rating of quality (good/fair/poor) done
for individual studies
Consistency
Degree to which reported effect sizes from included studies appear to have the
same direction of effect. This can be assessed through two main elements:
• Effect sizes have the same sign (that is, are on the same side of ‘‘no effect’’)
• The range of effect sizes is narrow
Directness
Relates to whether the evidence links the interventions directly to health outcomes. For a
comparison of two treatments, directness implies that head-to-head trials measure the
most important health or ultimate outcomes. Evidence is indirect if:
• It uses intermediate or surrogate outcomes instead of ultimate health outcomes.
In this case, one body of evidence links the intervention to intermediate
outcomes and another body of evidence links the intermediate to most important
(health or ultimate) outcomes
• It uses two or more bodies of evidence to compare interventions A and B, e.g.,
studies of A vs. placebo and B vs. placebo, or studies of A vs. C and B vs. C but
not A vs. B.
Indirectness always implies that more than one body of evidence is required to link
interventions to the most important health outcomes. Directness may be contingent on the
outcomes of interest.
Precision
Precision is the degree of certainty surrounding an effect estimate with respect to a given
outcome (i.e., for each outcome separately). If a meta-analysis was performed, this will be
the confidence interval around the summary effect size.
a Excerpted from Owens et al., 201046
Based on the approach used in the prior AHRQ review of therapies for children with ASD,43
we required at least three fair quality studies to be available to assign a low strength of evidence
rather than considering it to be insufficient. For determining the strength of evidence for
effectiveness outcomes, we only assessed the body of literature deriving from studies that
included comparison groups. We required at least one good study for moderate strength of
evidence and two good studies for high strength of evidence. In addition, to be considered
“moderate” or higher, intervention-outcome pairs needed a positive response on two out of the
three domains other than risk of bias. For determining the strength of evidence related to harms,
we also considered data from case series.
Once we had established the maximum strength of evidence possible based upon these
criteria, we assessed the number of studies and range of study designs for a given intervention-
outcome pair, and downgraded the rating when the cumulative evidence was not sufficient to
justify the higher rating. The possible grades were—
• High: High confidence that the evidence reflects the true effect. Further research is
unlikely to change estimates.
• Moderate: Moderate confidence that the evidence reflects the true effect. Further research
may change our confidence in the estimate of effect and may change the estimate.
• Low: Low confidence that the evidence reflects the true effect. Further research is likely
to change confidence in the estimate of effect and is also likely to change the estimate.
• Insufficient: Evidence is either unavailable or does not permit a conclusion.
Applicability
Finally, it is important to consider the ability of the outcomes observed to apply both to other
populations and to other settings (especially for those therapies that take place within a
clinical/treatment setting but are hoped to change behavior overall). Our assessment of
applicability included determining the population, intervention, comparator, and setting in each
study and developing an overview of these elements for each intervention category.
Peer Review and Public Commentary
Researchers and clinicians with expertise in behavioral, medical, social, psychological and
educational issues and individuals representing stakeholder and user communities were invited to
provide external peer review of this report; AHRQ and an associate editor also provided
comments. The draft report was posted on the AHRQ Web site for 4 weeks to elicit public
comment. We addressed all reviewer comments, revising the text as appropriate, and
documented changes and revisions to the report in a disposition of comments report that will be
made available 3 months after AHRQ posts the final CER on the AHRQ Web site.
Results
Article Selection
We identified few studies addressing interventions for adolescents and young adults with
autism spectrum disorders (ASD). Of the entire group of 4,855 citations identified, 1,035
required full text review (Figure 2). Of these 1,035 full-text articles reviewed, we retained 32
papers (comprising 32 unique studies) and excluded 1,003 papers. Reasons for article exclusion
are listed in Appendix F.
Figure 2. Disposition of studies identified for this review
This figure outlines the flow of articles identified for the review. We located a total of 4,855 citations. Of these, 1,035 required full-text review. Of the 1,035 full text articles reviewed, we retained 32 papers (comprising 32 unique studies) and excluded 1,003 papers. Papers could be excluded for multiple reasons, and a number were excluded because they were not relevant to the Key Questions (n=840), did not include individuals with ASD in our target age range of 13 to 30 years (n=834), did not include at least 20 adolescents or young adults with ASD or their family members (n=845), or were not original research (n=156).
KQ = Key Question; n = number
aOne paper47 reports two unique studies.
b Numbers do not tally as studies could be excluded for multiple reasons
Organization of Results
As noted, we classified studies by broad category of intervention (behavioral, educational,
vocational, adaptive/life skills, medical, and allied health). With the exceptions of studies of
behavioral, medical, and vocational interventions, which included at least two studies addressing
the same intervention, the other categories of interventions comprise single studies of unique
interventions. Most studies (n=14) also targeted core symptoms of ASD (Key Question 1) or
functional behavior/independent living skills (n=10) (Key Question 3). Nine studies, eight of
which addressed medical interventions, examined comorbidities commonly occurring with ASD,
which we defined broadly to encompass associated symptoms such as irritability (Key Question
2). Only studies of medical interventions addressed harms (Key Question 5).
One study addressed interventions targeting the transition process (Key Question 4), and two
assessed effects of an intervention on family outcomes (Key Question 6). Because questions
were addressed by a number of small, single studies of any given intervention, we discuss all
studies together in the following sections instead of divided by Key Question. This approach
allows us to present the findings of this disparate literature more clearly. We use headings to
indicate the outcomes (e.g., core symptoms, functional behavior, harms, etc.) targeted in each
study. It is nonetheless important to note that the studies in these categories typically assessed
different interventions, and therefore could not be combined for an assessment of strength of
evidence beyond insufficient for any specific intervention at this time.
We present findings beginning with an overview of the content of the literature as a whole,
including the range of study designs used, approaches assessed and participants included. The
detailed analysis of the literature provides further discussion and analysis of studies presented by
broad category of intervention. Studies also are described in more detailed summary tables in the
relevant section of text. For information on studies not included in the summary tables, please
see the evidence tables in Appendix D; for information on quality scores for each study, see
Appendix G.
Overview of the Literature
The 32 unique studies described in this review included 10 randomized controlled trials
(RCTs). Table 4 provides an overview of the characteristics of the literature overall.
Table 4. Overview of the literature addressing interventions for adolescents and young adults
with ASD
Characteristic
RCTs
Nonrandomized
Trials
Prospective
Cohort
Studies
Prospective Case
Series
Retrospective Case
Series
Cross-
sectional
Studies
Total
Literature
Total n:
10
3
5
9
4
1
32
Intervention Category
Behavioral
2
1
2
3
0
0
8
Educational
1
1
0
0
0
0
2
Adaptive/Life Skills
1
0
1
1
1
0
4
Vocational
0
2
1
0
1
1
5
Medical
5
0
0
2
1
0
8
Allied Health
1
0
0
3
1
0
5
Treatment Duration
<1 month
3
0
0
2
0
0
5
>1 to =3 months
5
1
2
4
0
0
12
>3 to =6 months
0
1
0
0
1
0
2
>6 to =12 months
2
0
1
2
0
0
5
>12 months
0
1
2
1
2
0
6
Not specified
0
0
0
0
1
1
2
Study Population
United States
5
1
2
5
3
1
17
Europe
3
2
3
2
1
0
11
Asia
2
0
0
2
0
0
4
Total N participants with ASD
341
114
200
296
233
1707a
2891
ASD = autism spectrum disorders; n = number; RCT = randomized controlled trial
a1,707 individuals with ASD included in one study reporting data from an administrative database48
We did not rate any study as good quality. Five studies were fair quality,49-53 and most
studies were poor quality.17, 47, 48, 54-77 Eighteen studies included comparison groups, and ten of
these studies were randomized. Most studies were conducted in the United States or Europe, and
participant ages across all studies ranged from 2 years to over 45 years. Only studies of medical
interventions reported harms data.
Studies of Behavioral Interventions
Key Points
• Eight behavioral studies examined different social skills and intensive behavioral
interventions and included individuals with ASD both with and without concomitant
intellectual disability or language deficiencies. All studies were of poor quality.
• Most studies reported short-term gains in social skills as reported by parents or within
study measures, but the diversity of the interventions precludes drawing a conclusion
about effectiveness across the studies for behavioral interventions as a whole.
• Few studies reported evidence of generalization of skills beyond the treatment context.
Overview of the Literature
We identified eight studies47, 61-64, 76, 77 of behavioral interventions in seven unique
populations (Table 5). Studies included two RCTs conducted in the United States61 and United
Kingdom,63 one nonrandomized controlled trial conducted in the United States,76 and three case
series conducted in Canada,62 the Netherlands,77 and Italy.64 One paper presented data from two
separate studies conducted in the United Kingdom and involving two unique groups of
participants.47 Individuals in both studies received the same computer-based social skills
software intervention, but comparators differed, and participants were randomized to
intervention or control groups in only one study.47 Five studies examined either individual or
group61, 62, 76 or computer-based intervention approaches47, 63 focused on social skill
development, including recognizing emotions, for individuals with ASD. One study conducted in
Italy examined the impact of intensive behavioral treatment from a semi-residential rehabilitation
center on adaptive behavior64 while another examined social and adaptive outcomes from an
individualized treatment program in the Netherlands.77
Participants ranged in age from 13 to 43 in the studies. One study64 did not provide precise
age data but notes that 34 participants were categorized as adolescents. Treatment duration
ranged from 2 weeks to 2 years. We rated all studies as poor quality. Appendix G provides the
quality ratings for each study.
Detailed Analysis
Behavioral Studies Addressing Core Symptoms of ASD
Individual or Group Social Skills Interventions
Most studies of behavioral interventions addressing effects on the core symptoms of ASD
were short term and included a small number of individuals (Table 5). Among studies examining
group-based social skills programs, one RCT examined the short-term outcome of a trial of a
manualized (i.e., has a published treatment manual) outpatient social skills program, the Program
for the Education and Enrichment of Relational Skills (PEERS).61 The study included 33
adolescents (mean age 14.6 years) with average cognitive abilities (mean intelligence quotient
[IQ] = 96.0 in treatment group and 88.3 in control group) randomized either to a 12-week
program of group social skills intervention or to a delayed treatment control group. A later 14-
week, nonrandomized trial of the PEERS program involved a separate group of 28 adolescents
(mean age 14.6) diagnosed with high-functioning autism.76 In both studies, participants in the
treatment groups improved on parent-rated measured of social skills compared with control
group participants, but limited teacher-rated measures indicated no differences between groups.
The latter study assessed 12 of 14 treated participants 14 weeks after the end of intervention;76
gains were maintained on most measures.
One prospective case series examined improvements in 28 hospitalized high-functioning
adolescents (mean verbal IQ = 102.98 ± 13.33, mean age = 17.68 ± 3.14) receiving
individualized treatment plans focused on psychoeducation.77 At followup after 12 months of
treatment, social and daily behavioral functioning improved on parent- and tutor-reported
measures as did ASD symptoms on self-reported measures. Participants did not report a change
in problems related to daily behavioral functioning. Another prospective case series examined
the impact of a 12-week social skills group for adolescents (mean age 14.6 years) with ASD.
Adolescents recruited from community clinics with verbal skills sufficient to participate in a
group intervention demonstrated parent-reported improvements related to problem behaviors and
autism specific social concerns.62
Computer-Based Social Skills Interventions
Among studies examining computer-based approaches, one RCT of a computer-based social
skills training for adolescents with ASD randomized 22 children (age 12 to 18) to either training
through 10 half-hour sessions with a computer program designed to train emotion recognition or
to a control group.63 The intervention group demonstrated fewer errors in recognizing the
emotion depicted within the program from pre- to post-training, and relative to controls
demonstrated improvement regarding emotion recognition via tasks presented within cartoons
and stories.
An additional publication reported on two separate studies, one nonrandomized trial and one
cohort study, with unique groups of participants. Both studies assessed emotion recognition
abilities following completion of the Mind Reading computer-based training program.47 In both
studies, adults with ASD completing the program demonstrated improvements in recognizing
faces and voices utilized in the training relative to the control group but did not demonstrate such
improvements in recognizing improvements outside of the tasks.
Intensive Behavioral Interventions
The one study examining an intensive behavioral approach reported on the impact of intensive
behavioral treatment from a semi-residential rehabilitation center on adaptive behavior.64 The
study included 34 adolescents (age range not provided) receiving intervention from autism
specific centers in Italy. Participants were reported to have improved on measures of
socialization and adaptive behavior.
Table 5. Key outcomes of behavioral studies addressing the core symptoms of ASD
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Mean/Yrs ± SD
IQ, Mean ± SD
Key Outcomes
Individual/Group-Based Social Skills Training
Lagueson et al.,76 2011
United States
G1: Immediate socials skills
training, 14/12 (28 week
followup)
G2: Delayed treatment
control, 14/14 (14 week
followup)
Quality: Poor
G1: 15.0 ± 1.0
G2: 14.3 ± 1.4
IQ (KBIT2)
G1: 94.1 ± 20.2
G2: 104.5 ± 18.8
• 14-week manualized intervention: Program for the
Education and Enrichment of Relational Skills with
followup 14 weeks postintervention for treatment group
participants.
• Adolescents with high-functioning ASD (diagnoses not
confirmed within study), ranging in age from 12 to 17
(mean = 14.6).
• Treatment group showed improvements on parent-
reported measures of social skills and interactions
compared with control group; limited teacher reports
showed no significant differences between groups.
• At 14-week followup, most gains maintained for
treatment participants; overall social skills continued to
improve based on parent-rated measures. Some
teacher-rated domains improved also.
• Quality considerations: nonrandom assignment to
groups; systematic diagnostic approach not reported
within study; attrition and treatment fidelity not
reported; differences in concomitant interventions not
reported; outcomes not coded by masked assessors.
Laugeson et al.,61 2009
United States
G1: Immediate social skills
training, 35 (total)/17
G2: Wait list, 35 (total)/16
Quality: Poor
G1: 14.6 ± 1.3
G2: 14.6 ±1.6
IQ (KBIT2):
G1: 96 ± 16.1
G2: 88.3 ± 21.1
• 12-week manualized intervention: Program for the
Education and Enrichment of Relational Skills.
• School-aged children of average intelligence.
demonstrated short-term improvements in social skills
knowledge, parent rated skills, and reported
engagement in social activity.
• Teacher-rated outcomes were not different for delayed
treatment control.
• Quality considerations: randomization method not
clearly described; systematic diagnostic approach not
reported within study; outcomes not coded by masked
assessors.
Verhoeven et al.,77 2011
Netherlands
G1: Social skills intervention,
28/28
Quality: Poor
G1: 17.68 ± 3.14
IQ (WAIS/WISC):
G1: 102.82 ± 13.33
(verbal)
98.36 ± 12.02
(performance)
• 12-month intervention associated with psychiatric
hospitals, focusing on fostering development,
improving behavioral functioning, well-being, and
reducing ASD symptoms and understanding role of
self-awareness in influencing treatment.
• Social and behavioral functioning improved in teacher -
and parent-reported measures.
• Participants reported decrease in ASD symptoms, but
no change in problems of daily behavioral functioning.
• Positive correlation between initial self-awareness and
improved social functioning; improved self-awareness
associated with parent-reported decrease in problems
in daily functioning but self-reported increase in
problems.
• Quality considerations: no comparison group;
intervention not fully described; measure of treatment
fidelity not reported; outcomes not coded by masked
assessors.
Table 5. Key outcomes of behavioral studies addressing the core symptoms of ASD (continued)
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Mean/Yrs ± SD
IQ, Mean ± SD
Key Outcomes
Individual/Group-based social skills training
Tse et al.,62 2007 Canada
G1: Social skills training with
emphasis on learning through
role play, 46/32
Quality: Poor
G1: 14.6 ±1.7
NR
• 12-week intervention for adolescents with substantial
verbal ability.
• Improvement in parent rated skill outcomes.
• Nonmanualized intervention, only parent report
outcomes noted.
• Quality considerations: no comparison group;
systematic diagnostic approach not reported within
study; participants not clearly characterized (no
cognitive or developmental measures); measure of
treatment fidelity not reported; differences in
concomitant interventions not reported; outcomes not
coded by masked assessors.
Computer-based social skills training
Golan et al.,47 2006 United
Kingdom
Study 1
G1: Home software users,
19/NR (21% drop out rate)
G2: Control, 22/NR
Quality: Poor
G1: 30.5 ± 10.3
G2: 30.9 ± 11.2
IQ (WASI, verbal):
G1: 108.3 ± 13.3
G2: 109.7 ± 10.0
• Individuals participating in home-based program
demonstrated improvement related to emotion
recognition of faces and voices within the study relative
to controls.
• Individuals did not perform differently on measures
assessing generalization of emotion recognition.
• Quality considerations: randomization method not
clearly described; systematic diagnostic approach not
reported within study; measure of treatment fidelity not
reported.
Golan et al.,47 2006 United
Kingdom
Study 2
G1: Software and tutor, 18/13
G2: Social skills course,
18/13
Quality: Poor
G1: 25.5 ± 9.3
G2: 24.4 ± 6.4
IQ (WASI, verbal):
G1: 105.7 ± 16.1
G2: 96.5 ± 15.5
• Individuals participating in home-based program plus
group intervention demonstrated improvement related
to emotion recognition of faces and voices within the
study relative to controls.
• Individuals did not perform differently on measures
assessing generalization of emotion recognition.
• Verbal IQ was significantly associated with
improvement.
• Quality considerations: nonrandom assignment to
groups; systematic diagnostic approach not reported
within study; inclusion/exclusion criteria not clearly
stated; measure of treatment fidelity not reported;
differences in concomitant interventions not reported.
Table 5. Key outcomes of behavioral studies addressing the core symptoms of ASD (continued)
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Mean/yrs ± SD
IQ, Mean ± SD
Key Outcomes
Computer-Based Social Skills Training
Silver et al.,63 2001
United Kingdom
G1: Computer sessions +
standard lessons, 12/10
G2: Standard lessons only,
12/11
Quality: Poor
G1: 13.9 ± 0.9
G2: 14.75 ± 2.0
IQ (BPVS):
G1: 10.67 ± 2.25
G2: 12.0 ± 3.33
• School-aged children and adolescents with
substantial verbal abilities demonstrated
improvement in emotion recognition after 10 half
hour sessions over 2 weeks.
• No measures of generalization or outcomes apart
from the study session were included.
• Quality considerations: randomization method not
clearly described; systematic diagnostic approach
not reported within study; differences in
concomitant interventions not reported; outcomes
data not collected from appropriate sources (self-
report only).
Intensive Behavioral Treatment
Valenti et al.,64 2010 Italy
G1: ABA-based intensive
behavioral therapy, 34/34
Quality: Poor
G1: NR, 34 identified as
postpubertal adolescents
25/34 identified as having
intellectual disability
• Study of treatment received within context of semi-
residential facility indexed gains related to
adaptive behavior.
• No control group was included, the participants
were very diverse, and the specific intervention
components were not well described.
• Parent satisfaction with the treatment program
was high on all measures.
• Quality considerations: no comparison group;
measure of treatment fidelity not reported;
differences in concomitant interventions not
reported; outcomes not coded by masked
assessors
BPVS = British Picture Vocabulary Scale; G = group; IQ = intelligence quotient; KBIT2 = Kaufman Brief Intelligence Test-
Second Edition; n = number; NR = not reported; SD = standard deviation; WASI = Wechsler Abbreviated Scale of Intelligence
Behavioral Studies Addressing Comorbidities
and Associated Symptoms
Individual/Group Social Skills Interventions
One prospective case series examined social outcomes and daily behavioral functioning in 28
high-functioning adolescents (mean verbal IQ = 102.98 ± 13.33, mean age = 17.68 ± 3.14)
undergoing individualized treatment at specialized psychiatric hospitals.77 Greater self-awareness
was correlated with increased social functioning; however, improvements in self-awareness after
treatment were correlated with increases in reports of problems in daily behavioral functioning
and psychological problems by self-report.
Behavioral Studies Addressing Independent Functioning
Intensive Behavioral Interventions
In the poor quality case series assessing the impact of intensive behavioral treatment,64
participants demonstrated modest improvements in standard measures of adaptive behavior over
a 2-year period. Female participants also had improved daily living and motor skills in this
uncontrolled study.
Behavioral Studies Addressing Family Outcomes
Intensive Behavioral Interventions
The same poor quality case series64 of intensive behavioral intervention reported family
satisfaction. The study included both adolescents and younger children and presented satisfaction
data for the two groups combined. Overall, parents were highly satisfied with most elements of
the program at year 1 and year 2, with median scores in the 4.5 to 10 range on scales ranging
from 1 to 6 or 1 to 10. The overall median score for the domain of “family participation”
increased slightly (8.0 to 8.5) as did scores on individual domain elements (“feeling of a having a
say in the matter,” 5.0 to 5.5; “involvement in school meetings,” 5.0 to 5.5). Scores in the
domain of “intervention outcome” remained stable for elements including “service to help
participant in facing daily problems” (5.0), “feeling confident about what to do” (5.0), and
“service to help participants’ quality of life” (5.0) but declined slightly on “service to help family
in coping with problems” (5.0 to 4.5).
Studies of Educational Interventions
Key Points
• Two poor quality studies evaluated educational approaches; the strength of the evidence
for effects of educational approaches is insufficient based on few poor quality studies
addressing disparate interventions.
• Strategies to increase reading comprehension were reportedly associated with some
improvement in one small, poor quality study.
• Neither of two vocabulary teaching methods was more effective in increasing nouns
learned by individuals with ASD and intellectual disability.
Overview of the Literature
Two studies, both of poor quality, examined educational interventions. One nonrandomized
controlled trial66 in the United States included 23 individuals ranging in age from 17 to 37 years
(mean = 26) with mean mental age scores of 3.3 years and mean language scores of 3.0 years.
Participants received language instruction using 2 methods of teaching over the course of 8
weeks, and investigators assessed outcomes including the number of nouns learned and retained.
One RCT65 was conducted in Canada and investigated procedural strategies to promote reading
comprehension and included 20 individuals with ASD (mean age = 15.1, mean Stanford-Binet
IQ = 88.15 ± 16.06). Appendix G provides the quality ratings for each study.
Detailed Analysis
Educational Studies Addressing Core Symptoms of ASD
One poor quality nonrandomized trial included 23 adults with ASD and intellectual disability
living in a residential treatment facility (Table 6).66 Participants ranged in age from 17 to 37
(mean = 26) and had mean mental age scores of 3.3 years and mean language scores of 3.0 years.
Investigators matched participants on chronological age, mental age and vocabulary scores, and
duration of stays in residential treatment and assigned groups to either analog language teaching
for three 15 minute individual sessions/week over 4 weeks or natural language teaching for three
45-minute group sessions/week over 4 weeks. After an assessment, participants crossed over to
the alternate training condition.
At the end of this second training phase, investigators assessed vocabulary retention. Neither
teaching condition was significantly better at increasing vocabulary (mean number nouns learned
in analog condition = 15.7, mean learned in natural language condition = 12.8); as expected,
generalization was greater during receptive as compared with expressive testing of noun
identification (p<0.001).66 Participants in both groups retained an average of 92.2 percent of
items learned at the final assessment. Participants’ level of intelligence was related to the amount
of generalization and to order of teaching. Participants in the upper range for mental age scores
learned more nouns with analog teaching first (mean nouns learned = 64.8) than did those in the
middle range (mean nouns learned = 10.3). Participants in the lowest mental age range
performed more poorly than others regardless of teaching condition order.
Table 6. Key outcomes of educational interventions addressing core symptoms of ASD
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Yrs, Mean ± SD
IQ, Mean ± SD
Key Outcomes
Elliott et al.,66 1991
United States
G1: 23/23
Quality: poor
G1: 26
G1: NR
• Analog and natural language teaching styles had
similar effects on increasing the number of nouns
learned by participants.
• Quality considerations: nonrandom assignment to
groups; inclusion/exclusion criteria not clearly
stated; attrition not reported; differences in
concomitant interventions not reported; outcomes
not coded by masked assessors.
G = group; NR = not reported; SD = standard deviation
Educational Studies Addressing Independent Functioning
A poor quality randomized study investigating the use of procedural strategies to promote
reading comprehension included 20 individuals with high-functioning ASD (mean age = 15.1,
mean Stanford-Binet IQ = 88.15 ± 16.06).65 Investigators presented participants with five stories
written at a roughly sixth grade reading level in various procedural facilitation conditions or two
control conditions. Procedural facilitation conditions included prereading, in which investigators
asked participants questions designed to elicit common knowledge relevant to the main focus of
the story; anaphoric cuing, in which a number of pronouns in each passage were underlined with
choices for appropriate or inappropriate referent words appearing below them; and a cloze (fill in
the blank) condition, in which blanks in sentences in each story could be completed by referring
to information presented in the preceding sentences. Passages were not altered in the control
condition. Investigators also asked participants questions about the stories’ main idea, facts from
the stories, and for their own retelling of the stories to gauge their understanding of the content.
Participants read and answered questions about all 5 stories, presented in random order for each
participant, in approximately 60 minutes, scored independently by masked assessors on a 1 (low)
to 25 (high) point scale. Reading comprehension scores ranged from 12.79 ± 6.33 in a control
condition to 15.41 ± 6.28 in the anaphoric cuing condition.
Overall, the study reported a medium size effect for procedural facilitation (F(4,76) = 2.49,
.2 = 0.12, p = 0.05). Post hoc analyses also revealed a significant effect of anaphoric cuing on
passage comprehension with a medium effect size (F(1.19) = 5.60, .2 = 0.42, p = 0.03). No
significant effects of prereading questions or cloze (fill in the blank) were apparent in the results.
Correlation analyses showed that anaphoric cuing worked best for individuals with lower
grammatical ability while prereading questions were most effective for students with high pre-
existing comprehension ability (Table 7).65
Table 7. Key outcomes of educational interventions addressing independent functioning
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Yrs, Mean ± SD
IQ, Mean ± SD
Key Outcomes
O’Connor et al.,65 2004
Canada
G1: 20/20
Quality: Poor
G1: 15.11 ± 0.99
G1: 88.15 ± 16.06
• Medium effect size for procedural facilitation and
anaphoric cuing styles as compared with baseline
(p = 0.05 and p = 0.03, respectively) among high
functioning individuals with ASD.
• No significant effect of prereading questions or
cloze style prompting.
• Quality considerations: randomization method not
clearly described; differences in concomitant
interventions not reported; outcomes not coded by
masked assessors.
ASD = autism spectrum disorders; G = group; SD = standard deviation
Studies of Adaptive/Life Skills Interventions
Key Points
• Four poor quality studies reported on disparate adaptive/life skills-focused interventions;
most assessed outcomes after short-term (<12 weeks) intervention, and at least two
included individuals with intellectual disability and ASD.
• Each study examined a different intervention, precluding a conclusion across studies on
the overall effectiveness of life skills interventions. Therefore, with four distinct, poor
quality studies, our ability to generate an estimate of effect is insufficient
• Nonetheless, each study reported some improvements in very specific life skills (e.g.,
shoe lacing, digital device use) after specific short-term interventions.
Overview of the Literature
We identified four studies, all of poor quality, of adaptive-focused interventions (Table 8).54-
57 Each study examined a different intervention, so the studies could not be combined to assess
effectiveness. Appendix G provides the quality ratings for each study. Treatment duration varied
from a day-long experiment to roughly 2 years in a residential facility. All studies were
conducted in the United States, and at least two included participants with intellectual
disability.54, 55 One crossover RCT assessed the number of trials needed to learn to lace a color
coded shoe versus a non-color coded shoe.55
One cohort study assessed an implementation of the TEACCH psychoeducational model
emphasizing farming and landscaping as vocational modalities and focused on teaching skills
and ameliorating behavioral problems.54 Outcomes assessed included measures of participant
skills and behaviors, level of environmental adaption and individualized programming, and
family satisfaction with treatment.
One case series57 investigated the use of personal digital assistants (PDAs) as memory aids
for high school students. Participants were all enrolled in a mainstream high school, had home
computers, and could operate a PDA independently. Outcomes measured included self-reported
performance of activities of daily living. A final case series addressed the transitioning process
by assessing effects related to implementing a classroom process—changing classrooms
throughout the school day—that individuals would be likely to encounter as they move to high
school or college.56
Detailed Analysis
Adaptive/Life Skills Studies Addressing Independent Functioning
A poor quality RCT55 demonstrated challenges related to utilizing highly salient, non-
criterion-related prompts (i.e., color coded targets) in teaching a specific shoe lacing skill to a
group of 20 young adolescents (mean age 12.3) with significant cognitive limitations (average
developmental age of 3.05). Participants were randomized to attempt to lace a shoe with color
coded laces and eyelets or a shoe with no color coding. Participants typically mastered the shoe
lace task more quickly in the color-coded condition but were not able to complete lacing a non-
color coded shoe as quickly, suggesting that participants may have concentrated more fully on
the color-coded prompt than the mechanics of the task.
One poor quality cohort study compared the effects of an experimental treatment setting, a
combined residential and vocational TEACCH-based training program model with three control
conditions: group homes, institutions, or family homes.54 The farm-based TEACCH program
emphasized farming and landscaping as vocational modalities and focused on teaching skills and
ameliorating behavioral problems. All participants were applicants to the TEACCH residential
program. Investigators used a part-random, part-clinical/administrative assignment procedure to
assign participants, matched on cognitive ability, autism and challenging behavior severity,
communication skills, and need for supervision, to the TEACCH treatment group (n = 6). The
other participants were living in a control setting (group homes, n = 10; institutions, n = 6; family
homes, n = 10). Participants were similar at baseline except in the case of individuals in family
homes, who were less likely to have experienced residential placement before age 18. The mean
age of all participants at baseline was 25 (range = 16 to 48 years). Eighty-five percent had severe
to profound intellectual disability (Vineland Adaptive Behavior Composite mean = 25), and most
had moderate to severe autism (mean CARS score = 36, range = 21 to 46). A majority of
participants (53%) had experienced residential treatment prior to age 18.
Research assistants measured outcomes at baseline and 12 months after treatment/residence
began for the TEACCH group. Outcomes assessed included measures of participant skills and
behaviors, level of environmental adaption and individualized programming, and family
satisfaction with treatment. The TEACCH program was rated as employing more communication
adaptations, socialization programming, preventive behavior management approaches, and visual
structure (all p<0.0004) than the other settings. TEACCH was also rated more highly in terms of
desirability of the living situation and use of programming (p = 0.0001 for both). Researchers
rated group homes as more desirable settings than institutions. Exploratory analyses of changes
in skills and behaviors showed variable results with few significant changes in skills or negative
behaviors over time across groups.54
One poor quality case series57 investigated the use of PDAs as memory aids for high school
students with ASD. While investigators do not report measures of IQ or mental age, participants
were all enrolled in a mainstream high school, had home computers, and could operate a PDA
independently. All 22 participants (age range 14 to 18, mean = 16.5) reported increases in self-
assessed performance of activities of daily living and satisfaction with the PDA after 8 weeks of
use following a brief training session (p<0.001). The majority reported independent daily use,
and examination of the PDAs showed a variable number of reminders entered. Outcome
measures were administered by study investigators who had also provided training in PDA use
and included one unvalidated tool.
Table 8. Summary of outcomes of adaptive/life-skills interventions
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Mean/Yrs ± SD
IQ, Mean ± SD
Key Outcomes
Gentry et al.,57 2010 United
States
G1: PDA use, 22/22
Quality: Poor
G1: 16.5 (range 14-18)
NR
• Self-rated scores on Canadian Occupational
Performance Measure increased from baseline
• 22/22 participants used PDA daily and reported
wanting to continue use; 16/22 could program
device independently.
• Quality considerations: no comparison group;
systematic diagnostic approach not reported
within study; participants not clearly characterized
(no cognitive or developmental measures);
differences in concomitant interventions not
reported; outcomes not coded by masked
assessors.
Jewell et al.,56 2007 United
States
G1: Adolescents with rotating
classroom schedule, 55/55
Quality: Poor
G1: 17.63 (14-22)
NR
• Rotating classroom schedule (students change
classroom throughout the day) had no significant
effect on the number of crisis events (baseline
mean = 2.44 ± 6.39, followup = 2.22 ± 5.88) or
time in crisis (baseline mean minutes = 40.27 ±
102.08, followup = 28.96 ± 65.47).
• Quality considerations: no comparison group; no
systematic diagnostic approach reported within
study; participants not clearly characterized (no
cognitive or developmental measures); attrition not
reported; outcomes not coded by masked
assessors.
Von Bourgondien et al.,54
2003
United States
G1: TEACCH-based program,
6/6
G2: Family home, 10/10
G3: Group home, 10/10
G4: Institutions, 6/6
Quality: Poor
G1: 23.7 ± 4.4
G2: 26.6 ± 5.1
G3: 27.8 ± 8.5
G4: 21.5 ± 5.0
85% of all participants
had moderate to severe
intellectual disability
• Outcomes rated by research assistants.
• Desirability of living situation and use of
programming rated more highly for TEACCH. than
other conditions; group homes rated more
desirable than institutions.
• Few significant changes in skills or negative
behaviors reported in exploratory analyses
• Parental satisfaction higher for TEACCH than
group homes (p=0.05); no difference in parental
satisfaction with institutions.
• Quality considerations: nonrandom assignment to
groups; systematic diagnostic approach not
reported within study; inclusion/exclusion criteria
not clearly stated; attrition not reported;
intervention not fully described; measure of
treatment fidelity not reported; differences in
concomitant interventions not reported; outcomes
not coded by masked assessors.
Table 8. Summary of outcomes of adaptive/life-skills interventions (continued)
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Mean/Yrs ± SD
IQ, Mean ± SD
Key Outcomes
Nelson et al.,55 1980 United
States
G1:Extra prompts/no extra
prompts
G2: No extra prompts/extra
prompts
G1+G2: 20/20
Quality: Poor
G1: 11.5 ± 3.0
G2: 13.1 ± 4.1
IQ (PEP developmental
age)
G1: 3.0 ± 0.7
G2: 3.1 v 0.9
• G1 completed lacing successfully in mean 108.7
trials plus 81.6 trials with the non-color coded
shoe.
• G2 completed lacing successfully in mean 137.2
trials plus 15.9 trials with the color coded shoe.
• Quality considerations: randomization method not
clearly described; systematic diagnostic approach
not reported within study; attrition not reported;
measure of treatment fidelity not reported;
differences in concomitant interventions not
reported; outcomes not coded by masked
assessors.
ASD = autism spectrum disorders; G = group; IQ = intelligence quotient; n = number; NR = not reported; PDA = personal digital
assistant; PEP = PsychoEducational Profile; SD = standard deviation; TEACCH = Treatment and Education of Autistic and
Communication related Handicapped Children
Adaptive/Life Skills Studies Addressing the Transitioning Process
One poor quality case series56 investigated the effect of a rotating classroom schedule (i.e.,
students change classrooms throughout the day) on behavior warranting crisis intervention
among 55 adolescent students at a school for individuals with ASD (mean age = 17.63, range 14
to 22). We considered this study as addressing transitional issues because it was intended to
examine the effects of a process (classroom changes) that individuals with ASD are likely to
encounter as they transition into high school or higher education settings.
The school used crisis management to handle violent, uncontrollable, self-abusive, or
dangerous behaviors. Crisis interventions consisted of progressive behavior management
techniques that could include restraint as a last resort. Investigators collected data on the number
of crisis interventions and time spent in interventions for 6 months prior to and 6 months
following the implementation of a rotating classroom schedule. Twenty-two of 55 adolescent
participants had crisis events prior to or after the classroom change. The number of crisis events
(mean prerotation = 2.44 ± 6.39, postrotation = 2.22 ± 5.88) and time in crisis were not
significantly different across time periods (mean minutes prerotation = 40.27 ± 102.08,
postrotation = 28.96 ± 65.47).
Adaptive/Life Skills Studies Addressing Family Outcomes
The cohort study54 investigating the TEACCH-based residential center54 also assessed family
satisfaction with treatment. Parents were significantly more satisfied with the TEACCH program
overall and with individuals’ level of community involvement compared with group homes
(p=0.05), but there was no difference in satisfaction with institutions and either the TEACCH
program or group homes. Parents of individuals in the TEACCH residence were also more
satisfied with the impact of the placement on the family than parents of individuals in other
groups.54
Studies of Vocational Interventions
Key Points
• Five poor quality studies assessed vocational interventions for adolescents and young
adults with ASD.
• Individual studies of different on-the job supports (broadly defined as services to promote
job placement and job retention) reported increased rates of employment in the
community relative to those without on-the-job supports. Because the individual studies
have not been replicated and are of poor quality, the strength of evidence (confidence that
future research will not change our understanding of the effect) for the effect seen is
insufficient, as more research is needed to quantify the degree to which these
interventions are effective, and under what circumstances.
• Despite positive results associated with other outcomes (quality of life, autism symptoms,
cognitive development) reported in individual studies, the poor quality of the studies,
assessment of unique outcomes in each study, and lack of replication lead to insufficient
strength of evidence until further studies are conducted that may confirm the observed
effects.
Overview of the Literature
We identified six papers reporting on five unique study populations and addressing the
impact of supported employment/vocational interventions on outcomes for adolescents and
young adults with ASD (Table 9). One study was a nonrandomized controlled trial conducted in
Spain and Germany.74, 75 Two prospective cohort studies were conducted in Spain72 and the
United Kingdom,73 and one case series was conducted in the United Kingdom17 and one cross-
sectional study was conducted in the United States.48 All studies were considered poor quality.
Appendix G provides the quality ratings for each study.
Interventions addressed in the studies all involved finding and implementing on-the-job
supports for young adults with ASD. Three of the studies focused on government-funded
supports,17, 48, 73 and two studies conducted in Spain and/or Germany focused on privately-funded
supports.72, 74, 75 Three studies included a comparison or control group that did not receive the
employment/vocational intervention,72-75 and two studies examined the impact of the
intervention on employment outcomes without a comparison group.17, 48
Detailed Analysis
Vocational Studies Addressing Core Symptoms
A poor quality nonrandomized trial reported in two papers74, 75 examined the impact of
supported employment (community-based jobs with no more than two individuals with ASD in
the workplace) versus sheltered workshops (defined as “piece work being performed in
segregated programs with only disabled coworkers”) on autism symptoms75 and quality of life74
of young adults with ASD (Table 9). Participants were 55 young adults who had received a
clinical diagnosis of autism. The study did not report participant recruitment procedures clearly.
Investigators assigned 26 participants to a sheltered workshop group and 21 to a supported work
group. It is unclear why the sum of number of participants in each group does not match the total
sample size.
The average age of participants was 21 years (mean = 21.07 ± 4.18, sheltered workshop
group; mean = 21.64 ± 3.75, supported employment group), and their average IQ scores were in
the mid-50s (mean = 55.52 ± 14.43, sheltered workshop group; mean = 57.41 ± 15.01, supported
employment group). There appeared to be more males in the supported employment group (84%)
than in the sheltered workshop group (69.2%), although the study did not assess group
differences in gender. Although individuals were matched by gender, autism symptom scores
(using the CARS), and IQ, participants were only eligible for the supported employment group if
they had an absence of severe behavior problems and acceptable professional and vocational
abilities. All of the jobs for those in the supported group were in the community with no more
than two individuals with ASD in the same work place. Youth in the supported group worked
between 15 to 30 hours a week, were paid competitive wages, and each had a job coach.
The average length of community employment at followup was 30 months. Differences
between the supported and sheltered workshop groups in autism symptoms or quality of life were
not significant before intervention. However, at followup, young adults who had participated in
the supported work program had reduced autism symptom and higher quality of life scores
relative to those who were in a sheltered workshop. Further, the autism symptom differences
were due to deterioration in the sheltered group over time, whereas the supported group had no
difference in autism symptoms scores from before to after intervention. In contrast, the sheltered
workshop group had no difference in quality of life over time, whereas the supported group had
quality of life scores that improved from before to after intervention. In sum, this study reports
that for young adults with autism, supported work in the community may ameliorate increases in
autism symptoms and improve quality of life relative to sheltered workshop work.74, 75
A related poor quality prospective cohort study from the same research group72 examined the
impact of supported employment in the community (supported work group) versus vocational
activities in a sheltered setting (no supported work group) on the cognitive development of
young adults with autism (Table 9). Participants included 44 young adults (32 men, 12 women)
who were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders,
FourthEdition (DSM-IV) criteria and who had CARS scores greater than 30. Participants were
randomly selected from the Spanish Program of Employment for Autistic People. The mean age
of participants was 25.52 years (SD = 3.35) for the supported work group and 24.32 (SD = 4.34)
years for the no supported work group. The average years of schooling was 5.31 (range = 3 to 7
years). The study did not present standardized IQ scores for the participants, but all participants
were required to score at about the 35th percentile on the Standard Progressive Matrices, a non-
verbal IQ test. Similar to earlier studies,74, 75 participants were eligible for the supported work
group if they had an absence of severe behavior problems and acceptable professional and
vocational abilities. All of the jobs for those in the supported work group were in the community,
with no more than two individuals with autism in the same work place. Youth in the supported
work group averaged 20 hours of work a week, were paid competitive wages, and each had a job
coach. The average length of community employment at followup was 30 months.
The “no supported work” group was on a waiting list for supported work and participated in
non-competitive vocational activities during the study period. It is unclear how many participants
were in each group. At the start of the study, there were no significant differences between the
supported work and no supported work groups in vocabulary (British Picture Vocabulary Scale),
IQ (Raven’s matrices), or autism symptoms (CARS). There were also no differences between
groups at this time on any of the 12 cognitive performance tasks which measured constructs such
as psychomotor speed, spatial recognition memory, and executive functioning (many of the tasks
were from the Cambridge Neuropsychological Tests: Automatic Battery). Results suggested that,
relative to the control group, the supported employment program was associated with
improvements over time in 8 of the 12 measures of cognitive functioning.72
Table 9. Key outcomes of vocational studies addressing core symptoms
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Yrs, Mean ± SD
IQ, Mean ± SD
Key Outcomes
Garcia-Villamisar et al.,72
2007
Spain
G1: Supported employment
G2: Wait list
Overall N: 44/44
Quality: Poor
G1: 25.52 ± 3.35
G2: 24.32 ± 4.34
IQ (Raven):
G1: 41.14 ± 4.45
G2: 42.23 ± 5.43
• Adults with ASD participating in a community work
program vs. a waitlisted group who participated in
non-competitive (i.e., sheltered) vocational
activities.
• Followup assessment was approximately 30
months after the start of the intervention.
• Relative to the waitlisted group, the supported
employment group experienced improvements
over time in 8 of the 12 measures of cognitive
functioning.
• Quality considerations: nonrandom assignment to
groups; attrition not reported; intervention not fully
described; measure of treatment fidelity not
reported; differences in concomitant interventions
not reported; outcomes not coded by masked
assessors.
Garcia-Villamisar et al.,74, 75
2000
Spain, Germany
G1: Sheltered work, 26/26
G2: Supported work, 25/21
Quality: Poor
G1: 21.07 ± 4.18
G2: 21.64 ± 3.75
IQ (Leiter):
G1: 55.52 ± 14.43
G2: 57.41 ± 15.01
• Adults with ASD participating in a community work
program had lower autism symptoms and higher
quality of life scores relative to those who were in
a sheltered workshop.
• Followup assessment was approximately 30
months after the start of the intervention.
• Quality considerations: nonrandom assignment to
groups; inclusion/exclusion criteria not clearly
stated; intervention not fully described; measure of
treatment fidelity not reported; differences in
concomitant interventions not reported; outcomes
not coded by masked assessors.
ASD = autism spectrum disorders; G = group; IQ = intelligence quotient; N = number; SD = standard deviation
Vocational Studies Addressing Independent Functioning
We identified two cohort studies17, 73 and one cross-sectional study48 examining the impact of
employment/vocational interventions on outcomes for adolescents and young adults with ASD
(Table 10). We rated all studies as poor quality.
In one cohort study conducted in the United Kingdom, the authors examined the outcome of
a 2-year supported employment scheme for high-functioning adults with autism or Asperger
syndrome.73 Participants in the supported employment scheme included 27 males and 3 females.
All participants had a formal diagnosis of autism or Asperger syndrome, a performance or verbal
IQ score above 70 (as measured by the Wechsler Adult Intelligence Scale), were actively seeking
work and able to travel independently, were capable of eventually maintaining employment with
minimal support, and had no psychiatric or physical problems that would adversely affect
employment. An additional 20 individuals (all male) who met the study criteria were contacted
and enrolled into a no-treatment comparison group. There were no significant differences
between the supported employment and comparison groups in age (mean = 31.1 years for the
supported employment group and 28.0 years for the comparison group), IQ, or vocabulary
(British Picture Vocabulary Test) at the start of the study.
The supported employment scheme included job finding and work preparation, educating
potential and existing employers and colleagues about ASD, and on-the-job supports. On-the-job
supports included assistance from a support worker with dealing with the social and occupational
requirements of a job and education about ASD for employers and work colleagues. The
frequency of supports decreased over the study period. Although the total study period covered
two years, and average amount of time that individuals were registered with the scheme was
17.03 months (range from 5 to 24 months). Over the 2-year evaluation period, young adults in
the supported employment group were significantly more likely to find paid employment than
those in the comparison group (63.3%vs. 25%), and they spent a greater amount of the study
time employed (27.09%of time employed for the supported employment group and 12.35% of
time employed for the comparison group). For those who were employed, the number of hours
worked per week did not differ between the supported work versus comparison group, however
the supported work group had higher wages per hour on average. There were no significant
differences between those who were and were not able to find work in IQ, vocabulary, social
understanding, or age. The investigators noted that the most important aspect of their supported
work program–and also the most expensive–was the “job finding” aspect, which included many
hours of making presentations to, meeting with, and negotiating with potential employers. The
authors also noted that funds are rarely available to subsidize the “job finding” component.
This same research group conducted a longer-term followup of their supported employment
scheme, now titled “Prospects.”17 This prospective cohort study examined whether the gains in
employment made during the first two years of the project73 persisted for up to 8 years and with a
larger cohort (recruited from three regional sites in the United Kingdom). In addition to the 30
young adults with ASD reported on in the earlier study,73 an additional 117 young adults who
began receiving services between 2002 and 2003 were added to the cohort. The mean age of
individuals added to the cohort was 31.4 years (standard deviation [SD] = 9.3). All had a clinical
diagnosis of autism or Asperger syndrome made by a psychiatrist or psychologist, and this
diagnosis was confirmed by using the Autism Diagnostic Interview in 20 percent of cases.
Thirteen of the 19 young adults in the original sample who found employment remained
employed 7 to 8 years later. For the young adults who were added since the original cohort, the
rate of employment remained high, ranging from 70.5 percent to 54.3 percent (depending on
regional site). The majority of employed young adults with ASD (84.7%) were generally happy
with their job.
A final cross-sectional study examined the impact of vocational/employment interventions
conducted in the United States.48 This study examined the effectiveness of vocational
rehabilitative services for adults with ASD compared with adults with other developmental
disabilities. The investigators identified 1,707 adults with ASD from national data obtained from
the U.S. Department of Education’s Office of Special Education and Rehabilitative Services.
Participants with ASD were identified using primary impairment causes for the disability in the
vocational rehabilitation dataset. Approximately 73 percent of the sample of adults with ASD
was 18 to 25 years of age; 15.5 percent was 25 to 34 years; and 11.1 percent was 35 years of age
or older. Eighty-four percent of adults were white, 12.8 percent were black, and 4.2 percent were
of Hispanic ethnicity. As this was an administrative database, data were not available about
autism symptoms or cognitive abilities. The study reported that the presence of on-the-job
supports (which could include counseling, on-the-job training, job search assistance, assessment
and diagnosis, and assistive technology) was associated with a higher likelihood of employment
in the community (competitive or supported), and that on-the-job supports were just as effective
in promoting employment for adults with ASD as for adults with other developmental
disabilities.
Table 10. Key outcomes of vocational studies addressing independent functioning
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Yrs, Mean ± SD
IQ, Mean ± SD
Key Outcomes
Lawer et al.,48 2009 United
States
G1: Vocational rehabilitation
service users, 1,707/1,707
United States
Quality: Poor
Age, range (%):
18-25 (73.4)
25-34 (15.5)
35-44 (8.1)
45-54 (2.5)
55-65 (0.5)
IQ: NR
• Presence of on-the job supports was associated
with a higher likelihood of employment in the
community (competitive or supported) for adults
with ASD.
• On-the job supports were as effective in promoting
employment for adults with ASD as for adults with
other developmental disabilities.
• Quality considerations: no comparison group;
systematic diagnostic approach note reported
within study; participants not clearly characterized
(no cognitive or developmental measures);
intervention not fully described; measure of
treatment fidelity not reported; differences in
concomitant interventions not reported; outcomes
not coded by masked assessors.
Howlin et al.,17 2005
United Kingdom
G1a: Pilot supported
employment program
participants (1995-1996),
30/30
G1b: Supported employment
program participants (2003-
2005), 117/89
Quality: Poor
G1a: 31.1 ± 9.1
G1b: 31.4 ± 9.3
IQ (Raven nonverbal):
G1a: 110.2 ± 17.6
G1b:110.7 v 19.5
• For adults in the 8-year followup (1995-1996
sample), 13 of 19 (68%) who had been previously
employed remained employed.
• For adults in the additional sample (2003-2005),
employment ranged from 70.5% to 54.3%,
depending on regional site.
• Quality considerations: no comparison group;
attrition not reported; differences in concomitant
interventions not reported; outcomes not coded by
masked assessors.
Mawhood et al.,73 1999
United Kingdom
G1: Supported employment
program, 30/30
G2: Control, 20/20
Quality: Poor
G1: 31.1 ± 9.1
G2: 28.0 ± 6.1
IQ (WAIS full scale):
G1: 98.8 ± 16.3
G2: 97.7 ± 20.4
• 2-year supported employment scheme for high-
functioning adults with autism or Asperger
syndrome.
• Adults in the supported work group were more
likely to find paid employment (63% vs. 25%) and
had higher wages per hour on average than a
control group.
• No differences between groups in number of
hours worked per week for those who worked.
• Quality considerations: nonrandom assignment to
groups; systematic diagnostic approach not
reported within study; differences in concomitant
interventions not reported; outcomes not coded by
masked assessors.
ASD = autism spectrum disorders; G = group; IQ = intelligence quotient; SD = standard deviation; WAIS = Wechsler Adult
Intelligence Scale
Studies of Medical Interventions
Key Points
• Eight studies of pharmacologic agents met our review criteria; four of these were RCTs
of fair quality. One additional RCT and three case series were poor quality.
• The strength of evidence related to challenging or repetitive behaviors and harms for each
of the agents assessed is insufficient based on no good studies and lack of replication.
• Little evidence supports the use of medical interventions in the adolescent and young
adult population; most studies focused on the use of medications to address specific
challenging behaviors.
• Studies of risperidone reported improvements in aggression, irritability/agitation,
repetitive behavior, sensory motor behaviors, and overall behavioral symptoms in
participants receiving risperidone.
• A placebo-controlled crossover study reported that haloperidol significantly improved
hyperactivity/defiance ratings, but no significant difference was found for
irritability/agitation or other symptoms.
• Studies of serotonin reuptake inhibitors (SRIs) had inconsistent results: an RCT of
fluvoxamine reported decreases in repetitive behavior, aggression, autistic symptoms, and
language usage and case series addressing sertraline, fluoxetine, and clomipramine
reported some benefits, while a crossover study of clomipramine versus placebo reported
no significant differences in autistic symptoms between groups.
• A crossover study of naltrexone reported no significant improvements in problem
behavior and worsening of stereotyped behavior with naltrexone compared with placebo.
• Harms reported across all studies included sedation, weight gain, fatigue, self-injurious
behavior, constipation, anxiety, and insomnia.
Overview of the Literature
We identified a total of eight studies of medical interventions.50-53, 67-69, 71 All eight of these
were studies of pharmacological agents. Overall, no studies were good quality, four were fair
quality,50-53 and four were poor quality.67-69, 71 Appendix G provides the quality ratings for each
study.
Three RCTs addressed the efficacy of antipsychotic medications (Table 11).50, 51, 67 Two were
conducted in the United States, and one in Canada. All of these RCTs were conducted in
academic clinic settings using institutional and grant funding, and one was fair quality51 and two
poor.50, 67
One fair quality RCT was conducted in an academic clinic in the Netherlands and
investigated an opiate antagonist (Table 12).53 Funding for the study came from institutional and
grant sources. Five studies investigated SRIs (Table 13).50, 52, 68, 69, 71 Two studies were fair
quality,50, 52 and the balance were poor.68, 69, 71 These studies included two RCTs;50, 52one was
conducted in the United States and one in Canada. Three poor quality case series were conducted
in the United States.68, 69, 71 All five of these studies were conducted in academic clinic settings
using institutional and grant funding.
Detailed Analysis
Medical Studies Addressing Comorbidities and Associated Symptoms
We summarize results of studies of medical interventions meeting our criteria below. The
Introduction section of the report contains a description of the mechanism of action of these
drugs.
Antipsychotics
Three studies addressed the efficacy of antipsychotics (Table 11).50, 51, 67 One fair quality
RCT51 assessed the efficacy and safety of risperidone in adults with autistic disorder or pervasive
developmental disorder-not otherwise specified (PDD-NOS). Inclusion criteria were being an
adult, having an Autistic Disorder or PDD-NOS diagnosis based on DSM-IV criteria, and at least
“moderate” symptom severity on the Clinical Global Impression of Severity (CGI-S) Scale.
Participants had either a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) compulsive
subscale score greater than 10, a Self-injurious Behavior Questionnaire (SIB-Q) score of 25 or
greater, or a Ritvo-Freeman Real-life Rating Scale overall score of 0.20 or more. Exclusion
criteria included a diagnosis of schizophrenia or psychosis, or any significant acute medical
condition. The experimental design was a 12-week randomized, double-blind, placebo-controlled
phase followed by a 12-week open-label risperidone treatment phase for patients from the
placebo group. Subjects were off all psychiatric medications for more than 4 weeks before the
trial started.
Risperidone dosing began with 1 milligram (mg) at night and advanced to twice daily dosing,
increasing every 3 to 4 days by 1 mg/day, up to a maximal clinical effect or a maximum dose of
10 mg/day. Outcome measures included a modified version of the Y-BOCS, the SIB-Q, the
Ritvo-Freeman Real-life Rating Scale, visual analog scales of different mood states, the Clinical
Global Impression of Improvement (CGI-I), vital signs, and monitoring for extrapyramidal
effects or other adverse effects. Subjects with a CGI-I score of “much improved” or “very much
improved” were considered responders. The primary outcomes were global improvement (CGI),
repetitive behavior (Y-BOCS), aggression (SIB-Q), and social relatedness (Ritvo-Freeman).
The mean age of the 31 subjects who began the trial was 28.1 years (SD 7.3) and mean full-
scale IQ was 54.6 (SD 23.9). Only 24 subjects completed the trial. Fifty seven percent (8 of 14
subjects) were considered responders in the risperidone group, while none (0 of 16 subjects) in
the placebo group were responders (p<0.002). Repetitive behavior as measured by Y-BOCS
improved over time (p<0.001) for the risperidone group compared with the placebo group at
each time point. This result was consistent with improvements over time in the open-label phase
(p<0.03). Aggressive behavior as measured by SIB-Q improved over time (p<0.001) for the
risperidone group compared with the placebo group. This result was consistent with
improvements over time in the open-label phase (p<0.05). Symptomatic improvements as
measured by the Ritvo-Freeman for the risperidone group compared with placebo were
significant over time for sensory motor (p<0.004), affectual reactions (p<0.001), and overall
score (p<0.05); however differences for social relationships, sensory responses, or language were
not significant.
These results were consistent with the improvements over time in the open label phase except
that sensory responses reached significance in the open label phase. Clinician-rated visual analog
scales were significantly decreased in the risperidone group compared with placebo for “anxious
or nervous” (p<0.02), “depressed” (p<0.03), and “irritable” (p<0.01); however there were no
significant differences for “calm,” “eye contact,” “happy,” “restless,” “social interaction,”
“talkative,” or “tired.” Seven subjects did not complete the trial (3 in the risperidone arm and 4 in
the placebo arm), with six subjects dropping out due to lack of improvement or agitation, and
one subject in the risperidone arm with abnormal gait.
A poor quality crossover study addressed the safety and efficacy of risperidone in children,
adolescents, and adults with intellectual disability.67 Inclusion criteria were age 6 to 65 years; a
6-month or longer history of aggression, property destruction, or self-injury; and Aberrant
Behavior Checklist-Community (ABC-C) scales above normal range. Exclusion criteria included
a history of hypersensitivity to risperidone, neuroleptic malignant syndrome, seizures within the
last year, degenerative brain disease, and problematic living/social situation. Subjects were free
of all psychiatric medications for at least 2 weeks prior to entering the trial. The placebo-
crossover design began with a placebo run-in phase (3 to 5 weeks). The study randomized
participants to low dose risperidone (1 mg/day for children and adolescents, 2 mg/day for adults)
or high dose risperidone (0.05 mg/kg/day), divided into a twice-daily schedule. The first
treatment period started with 2 weeks of titration followed by 4 weeks at a constant dose. For the
second treatment period, subjects crossed over to the other dose with 2 weeks of titration
followed by 4 weeks at a constant dose. The crossover study design changed to an open-label
design after a second placebo period (3 to 5 weeks) followed by 24 weeks of unblinded
maintenance at the better risperidone dose.
Outcome measures included the ABC-C, the Dyskinesia Identification System Condensed
User Scale, the Neuroleptic Side Effects Checklist, routine laboratory tests, and weight.
Prolactin, hemoglobin A1c, and lipid profile were measured in a subset of the study subjects (n =
20). The primary outcome was the ABC-C Irritability subscale score.
Of the forty subjects, all had intellectual disability, 28 (70%) met DSM-IV criteria for autistic
disorder, and 8 (20%) met DSM-IV criteria for PDD-NOS. The mean age was 22.0 years (SD
13.1). Twenty-three (57.5%) of subjects responded fully, and 35 (87.5%) had at least a partial
response. The study defined a 50 percent reduction in the ABC-C Irritability/Agitation subscale
score as a full response and a 25 percent reduction as a partial response. The mean ABC-C
Irritability/Agitation subscale score was significantly different for both treatment periods
compared with the second placebo period (p = 0.0002). There was no significant dose effect for
the ABC-C Irritability/Agitation subscale between low- and high-dose risperidone (p = 0.13).
A fair quality crossover study50 investigated the efficacy of haloperidol for the treatment of
autism. Inclusion criteria were a DSM-IV diagnosis of autism; a recommendation for
pharmacotherapy based on initial assessments; and never previously having completed an
adequate trial of haloperidol or the SRI clomipramine. Exclusion criteria were not reported. The
study design was a double-blind, placebo-controlled, crossover with random assignment to 7-
week treatment phases of haloperidol, clomipramine, and placebo. Haloperidol dosing started at
0.25 mg at bedtime and increased in 0.25 mg increments every 2 days until the dose was 0.50 mg
twice daily, then further 0.25 mg adjustments were made every 3 to 4 days based on clinical
assessment. The dose was reduced to the last dose tolerated if adverse effects were experienced.
There was a dosage taper during week 7 of each treatment phase. There were one-week placebo
washout periods between each treatment phase. No other psychotropic drugs were allowed
except benztropine. Outcome measures included the CARS, the Aberrant Behavior Checklist
(ABC), the Dosage Treatment Emergent Symptom Scale, and the Extrapyramidal Symptom
Rating Scale.
We summarize results for haloperidol and placebo here and address clomipramine results
below (see Serotonin Reuptake Inhibitor section). Of the 37 subjects recruited, 36 (mean age =
16.3 years) were included in final analyses. The mean daily dose of haloperidol was 1.3 mg. The
mean duration of haloperidol treatment was 5.8 weeks with 23 of 33 (69.7%) subjects
completing the 7-week treatment phase. Seven of 10 subjects who discontinued had adverse
effects (see Harms section below). The mean duration of placebo treatment was 5.4 weeks with
21 of 32 (65.6%) subjects completing the 7-week phase; 1 of 9 subjects who discontinued had
adverse effects which only included nose bleeds (n = 1). The other 8 subjects discontinued due to
lack of improvement in symptoms. Haloperidol versus placebo was significant for reductions in
ABC Hyperactivity/Defiance scores (p<0.05), but not for the other ABC subscales. The study did
not report statistical comparisons of haloperidol versus placebo for the CARS, Extrapyramidal
Symptom Rating Scale, or Dosage Treatment Emergent Symptom Scale. The investigators note
that carry-over of effects between treatment phases may have affected results in this crossover
design, especially with the short one-week washout. Other comparisons between haloperidol and
placebo were not discussed.
Table 11. Key outcomes of studies assessing antipsychotics
Author, Year,
Country
Groups, N
Enrollment/N Final
Study Quality
Mean Age,
Years ± SD
Mean IQ ±
SD
Outcome Measure/
Baseline Scores, Mean ±
SD
Outcome Measure/Post-
Treatment Scores, Mean ±
SD
Quality Considerations
Hellings et al.,67 2006
United States
G1+G2: Placebo
phase, then dose
risperidone, followed
by crossover to the
other risperidone
dose, then another
placebo phase
Placebo I phase: 3-5
weeks of placebo, n =
40
Acute Dose phase:
G1 Low dose (n = 39)
or G2 high dose
risperidone (n = 36)
Placebo II phase: 3-5
weeks of placebo, n =
33
Maintenance phase:
Optimal dose
risperidone, n = 32
Quality: Poor
G1+G2: 22 ±
13.1
NR, 40/40
with
intellectual
disability
ABC-C Irritability:
G1+G2, Placebo I phase:
19.16 ± 9.96
G1+G2, Placebo II
phase: 18.23 ± 12.36
ABC-C Irritability:
G1, Low dose acute
phase: 11.15 ± 9.28
G2, High dose acute
phase: 13.31 ± 8.92
p = 0.13 G1 vs. G2
p = 0.0002 G1+G2 Acute
phase vs. G1+G2 Placebo II
Maintenance phase scores
only reported graphically
Quality considerations:
inappropriate comparison
group; treatment adherence
not reported
Table 11. Key outcomes of studies assessing antipsychotics (continued)
Author, Year,
Country
Groups, N
Enrollment/N Final
Study Quality
Mean Age,
Years ± SD
Mean IQ ±
SD
Outcome Measure/
Baseline Scores, Mean ±
SD
Outcome Measure/Post-
Treatment Scores, Mean ±
SD
Quality Considerations
Remington et al.,50
2001
Canada
G1: Clomipramine
G2: Haloperidol
G3: Placebo
Overall N: 37/36
Quality: Fair
Overall: 16.3
(SD NR)
NR
CARS
Overall: 41.8 ± 7.1
CARS:
G1: 37.8 ± 8.7
G2: 36.7 ± 6.1
G3: 39.4 ± 7.0
p<0.05, G2 vs. baseline
ABC reported only
graphically
Quality considerations:
participants not clearly
characterized (no cognitive
or developmental
measures); outcomes not
coded by masked assessors
McDougle et al.,51
1998
United States
G1: Risperidone,
15/12
G2: Placebo,16/12
G2a: Open label
risperidone following
placebo, n = 15
Quality: Fair
G1+G2: 28.1 ±
7.3
G1+G2:
54.6 ± 23.9
Y-BOCS, compulsion:
G1: 16.5 ± 3.58
G2: 14.29 ± 3.50
G2a: 14.27 ± 2.92
SIB-Q:
G1: 47.8 ± 19.5
G2: 37.7 ± 11.9
G2a: 32.43 ± 15.89
Y-BOCS, compulsion:
G1: 12.77 ± 3.63
G2: 14.35 ± 3.02
p<.001, G1 vs. G2
G2a: 11.47 ± 3.64
p<0.03, G2a vs. BL
SIB-Q:
G1: 24.2 ± 9.5
G2: 32.8 ± 15.0
p<0.001, G2 vs. G1
G2a: 23.07 ± 13.45
p<0.05, G2a vs. BL
Quality considerations:
treatment adherence not
reported
ABC = Aberrant Behavior Checklist; ABC-I = Aberrant Behavior Checklist-Community Rating Scale-Irritability; ASD = autism
spectrum disorders; CARS = Childhood Autism Rating Scale; G = group; IQ = intelligence quotient; n = number; NR = not
reported; SD = standard deviation; SIB-Q = Self-Injurious Behavior Questionnaire; Y-BOCS=Yale-Brown Obsessive
Compulsive Scale
Opioid Receptor Antagonists
One study of an opioid receptor antagonist met our review criteria (Table 12).53 This fair
quality randomized, double blind crossover study tested the efficacy and safety of naltrexone on
self-injurious behavior and other autistic symptoms in intellectually disabled adults. Inclusion
criteria included a diagnosis using the Diagnostic and Statistical Manual of Mental Disorders,
Third Edition, Revised (DSM-III-R) criteria that was agreed upon by two clinicians. The study
also required that participants’ level of social impairment had to go beyond what was expected
by the severity of their intellectual disability, although the details of this determination were not
reported. The study also included a subgroup with moderate to high levels of self-injurious
behaviors, even though they did not meet criteria for autistic disorder. No exclusion criteria were
reported.
Concurrent medications, including antipsychotics, were held stable. The study randomized
participants to naltrexone or placebo with a 2-week single-blinded placebo period followed by a
single dose of naltrexone (100 mg) with placebo for the remainder of that week. This phase was
followed by a 4-week treatment period, a 4-week washout period, and finally a crossover to the
second 4-week treatment period. The first cohort received naltrexone 50 mg/day, but the dose for
the second cohort was changed to naltrexone 150 mg/day. Outcome measures included the ABC;
a clinician-rated checklist individualized to self-injurious behavior, stereotyped, and compulsive
behaviors of each subject; the CGI-I scale; direct observation for a subgroup of 11 subjects; and
laboratory analyses (liver function tests, plasma beta-endorphin, and plasma cortisol levels). The
primary outcome was self-injurious behavior.
Of the 33 subjects that participated, 24 had autistic disorder and 9 did not. Participants mean
age was 29 years (SD = 6), and IQ was not reported. Eleven subjects were taking antipsychotics
with the dose held steady during the study. The single dose had no effect on the clinician-rated
questionnaire, direct observation, self-injurious behavior, or plasma beta-endorphins. Plasma
cortisol was significantly increased (p = 0.006) for naltrexone compared with placebo.
Longer term treatment (4 weeks) with naltrexone resulted in a significant increase in
stereotypy as measured by the ABC stereotypy subscale. No changes in any of the other outcome
measures were significant. The study did not report comparative statistics, but the CGI scale
indicated that placebo was superior to 50 mg/day naltrexone in 12 of 18 subjects. The CGI scale
showed that 50 mg/day of naltrexone was better than placebo in only 4 of 18 subjects, while
placebo was superior in 12 of 18 subjects. The CGI scale also showed that 150 mg/day of
naltrexone was better than placebo in 5 of 14 subjects, while placebo was superior in an equal
number of subjects (5 of 14). There were no significant correlations between behavioral changes
after the single dose of 100 mg naltrexone and the 4-week treatments with naltrexone (50 mg or
150 mg). Further analyses with groups divided into subjects with concurrent antipsychotic and
subjects without did not yield any significant effect for naltrexone versus placebo.
Table 12. Key outcomes of studies assessing opioid receptor antagonists
Author, Year,
Country
Groups, N
Enrollment/N Final
Study Quality
Mean Age,
Years ± SD
Mean IQ ±
SD
Outcome Measure/
Baseline Scores, Mean ±
SD
Outcome Measure/Post-
Treatment Scores, Mean ±
SD
Quality Considerations
Willemsen-Swinkles
et al.,53 2005
Netherlands
G1+G2: 4 week
naltrexone phase for
cohorts 1 (50mg daily)
and 2 (150mg daily)
(ASD patients only)
G3+G4: 4 week
placebo phase for
cohorts 1 and 2 (ASD
patients only)
Overall N: 33/31
Quality: Fair
Overall: 29 ±
6.0
NR
ABC Stereotypy
G1+G2: 9.7 ± 4.7
G3+G4: 8.3 ± 5.2
ABC Stereotypy
G1+G2: 10.0 ± 4.7
G3+G4: 9.0 ± 4.8
p = 0.018, G1+G2 vs.
G3+G4
Quality considerations:
randomization method not
clearly described;
participants not clearly
characterized (no cognitive
or developmental
measures); treatment
adherence not reported;
differences in concomitant
interventions not reported
ABC = Aberrant Behavior Checklist; ASD = autism spectrum disorders; G = group; IQ = intelligence quotient; mg = milligrams;
n = number; NR = not reported; SD = standard deviation
Serotonin Reuptake Inhibitors
Five studies focused on SRIs met our criteria (Table 13).50, 52, 68, 69, 71 One fair quality RCT52
investigated the efficacy of fluvoxamine in adults with autistic disorder. Inclusion criteria were
adults with a diagnosis of autistic disorder based on the DSM-III-R. Exclusion criteria were a
DSM-III-R diagnosis of schizophrenia, psychotic symptoms, illicit substance abuse within the
prior 6 months, “notable” medical conditions, seizure disorder, or pregnancy. Participants were
not on any psychotropic medications for at least 6 weeks prior to starting the trial. The study
randomized participants to placebo or fluvoxamine. Fluvoxamine was initiated at 50 mg daily
and increased 50 mg every 3 to 4 days to maximum clinical response or a maximum dose of 300
mg/day. Outcome measures included the Y-BOCS, the maladaptive subscales of the Vineland
Adaptive Behavior Scales, the Brown Aggression Scale, the CGI-I, and the Ritvo-Freeman Real-
Life Rating Scale.
All 30 participants (15 fluvoxamine, 15 placebo) completed the 12-week trial. The mean age
was 30.1 years (SD 7.1) for the fluvoxamine group and 30.1 years (SD 8.4) for the placebo
group. The mean daily dose was 276.7 mg/day (SD 41.7) for the fluvoxamine group and 283.3
mg/day (SD 36.2) for the placebo group (difference not significant). Global improvement as
measured by CGI-I was higher for fluvoxamine compared with placebo (p<0.001). Subjects were
classified as responders if the CGI-I scores were “very much improved” or “much improved.”
There were significantly more responders (p<0.001) in the fluvoxamine group (8 of 15 subjects)
compared with the placebo group (0 of 15). Scores for the fluvoxamine group improved more
than those for the placebo group for the Y-BOCS (p<0.001), Vineland maladaptive subscales
(p<0.001), Brown Aggression Scale (p<0.03), overall Ritvo-Freeman Scale (p<0.04), and Ritvo-
Freeman Scale language usage subscale (p<0.008).
Another fair quality study50 used a double-blind, placebo-controlled crossover design to
investigate the efficacy of clomipramine and haloperidol for the treatment of autism. Inclusion
criteria were a DSM-IV diagnosis of autism; a recommendation for pharmacotherapy based on
initial assessments; never previously having completed an adequate trial of haloperidol or
clomipramine. Exclusion criteria were not reported. Investigators randomized participants to 7-
week treatment phases of haloperidol, clomipramine, and placebo. Clomipramine dosing started
at 25 mg at bedtime and increased in 25 mg increments every 2 days until the dose was 50 mg
twice daily, then further 25 mg adjustments were made every 3 to 4 days based on clinical
assessment. The dose was reduced to the last dose tolerated if adverse effects were experienced.
There was a dosage taper during week 7 of each treatment phase and 1-week placebo washout
periods between each treatment phase. No other psychotropic drugs were allowed except
benztropine. Outcome measures included the CARS, the ABC, the Dosage Treatment Emergent
Symptom Scale, and the Extrapyramidal Symptom Rating Scale. Adverse effect outcomes were
changes in stereotypy as measured by the Extrapyramidal Symptom Rating Scale and toleration
of adverse effects which was measured by continuation of each treatment phase.
We summarize results for clomipramine and placebo here and haloperidol results above (see
Antipsychotic section). Of the 37 subjects recruited, 36 (mean age = 16.3 years) were included in
final analyses. The mean daily dose of clomipramine was 128.4 mg. The mean duration of
clomipramine treatment was 4.5 weeks with 12 of 32 (37.5%) subjects completing the 7-week
treatment phase; 12 of 20 subjects who discontinued did so at least partially because of adverse
effects (see Harms section below).
The mean duration of placebo treatment was 5.4 weeks with 21 of 32 (65.6%) subjects
completing the 7-week treatment phase. One of 9 subjects who discontinued had adverse effects
which only included nose bleeds (n = 1). The study did not report statistical comparisons for
clomipramine versus placebo for the CARS, Extrapyramidal Symptom Rating Scale, or Dosage
Treatment Emergent Symptom Scale. The study did not report on the effects of clomipramine
compared with placebo for ABC subscales. The investigators note that carry-over of effects
between treatment phases may have affected results in this crossover design, especially with the
short 1 week washout.
One poor quality study69 assessed the efficacy and tolerability of clomipramine using a
prospective open-label case series design over 12 weeks. The inclusion criterion was a DSM-IV
diagnosis of a pervasive developmental disorder (autistic disorder, Asperger disorder, and PDD-
NOS). Subjects were excluded if they had any additional DSM-IV diagnosis other than
intellectual disability, had abused illicit drugs within 6 months, were pregnant, or had an acute
medical illness. Clomipramine was initially dosed at 50 mg daily, and then increased by 50 mg
every 3 to 4 days up to the maximum clinical response or a maximum dose of 250 mg daily. No
psychotropic medications were allowed except antiepileptic medication which were held stable
and chloral hydrate as needed for agitation. Outcome measures included the Y-BOCS, Brown
Aggression Scale, Ritvo-Freeman Real-Life Rating Scale (sensory motor behaviors, social
relationship, affectual reactions, sensory responses, and language subscales), and CGI-I. Of the
35 subjects, 33 completed the study and were taking a mean dose of 139 mg (SD 50). There was
a significant improvement (p<0.001) in CGI-I global symptoms over time with clomipramine
treatment. Of the 33 subjects completing the trial, 18 (55%) were responders as determined by
CGI score of “very much improved” or “much improved.” Clomipramine treatment significantly
reduced (p<0.001) repetitive thoughts and behaviors as measured by Y-BOCS. Aggression as
measured by the Brown Aggression Scale significantly decreased (p<0.001) over time with
clomipramine treatment. Clomipramine treatment significantly improved (p<0.001) autistic
symptoms as measured by the Ritvo-Freeman Scale overall score, as well as all each subscale.
The two subjects not completing the trial withdrew due to agitation in one individual and
abdominal cramping in the second participant. There was no placebo control group to compare
with the clomipramine treatment group in this open-label trial.
Another poor quality, 12 week open-label prospective case series68 investigated the efficacy
and tolerability of sertraline. Inclusion criteria were a DSM-IV diagnosis of autistic disorder,
Asperger disorder, or PDD-NOS; a minimum Y-BOCS score (> 15 for verbal subjects, >7 for
nonverbal subjects); minimum of score of 0.20 on the Ritvo-Freeman scale, minimum score of
25 on the SIB-Q; and a minimum of 5 on the Vineland Maladaptive Behavior Scale, part 2.
Sertraline was initially dosed at 50 mg daily, and then increased by 50 mg every week to a
maximum clinical response, maximal dose tolerated, or maximum dose of 200 mg daily. The
study allowed no psychotropic medications except chloral hydrate as needed for agitation.
Outcome measures included the Y-BOCS, SIB-Q, Ritvo-Freeman Real-Life Rating Scale, and
CGI-I. Of the 42 subjects, 37 completed the trial. The mean sertraline dose was 122.0 mg (SD
60.5). Of the 42 subjects starting the trial, 24 (57%) were considered responders based on CGI-I
score of “very much improved” or “much improved.” Five subjects withdrew from the study:
three due to anxiety/agitation, one due to syncope, one due to noncompliance. There was no
placebo control group for comparison of possible therapeutic effects or adverse events.
Finally, a poor quality retrospective case series71 studied the therapeutic effects and
tolerability of fluoxetine and included 23 individuals with ASD (mean age 15.9 ± 6.2). Most
participants (21/23) had concomitant intellectual disability. Participants received up to 80
mg/day of fluoxetine for a mean of 189 ± 153 days. CGI ratings of overall clinical severity
improved in 15 participants as did ratings of perseverative or compulsive behavior.
Table 13. Key outcomes of studies assessing SRIs
Author, Year,
Country
Groups, N
Enrollment/N Final
Study Quality
Mean Age,
Years ± SD
Mean IQ ±
SD
Outcome Measure/
Baseline Scores, Mean ±
SD
Outcome Measure/Post-
Treatment Scores, Mean ±
SD
Quality Considerations
Remington et al.,50
2001
Canada
G1: Clomipramine
G2: Haloperidol
G3: Placebo
Overall N: 37/36
Quality: Fair
Overall: 16.3
(SD NR)
NR
CARS
Overall: 41.8 ± 7.1
CARS:
G1: 37.8 ± 8.7
G2: 36.7 ± 6.1
G3: 39.4 ± 7.0
p<0.05, G2 vs. baseline
ABC reported only
graphically
Quality considerations:
participants not clearly
characterized (no cognitive
or developmental
measures); treatment
adherence not reported;
outcomes not coded by
masked assessors
McDougle et al.,68
1998
United States
G1: Sertraline, n =
42/37
G1a: AD
G1b: AS
G1c: PDD NOS
Quality: Poor
26.1 ± 5.8
60.5 ± 22.7
(28 with
intellectual
disability)
Y-BOCS, total score:
G1a: 16.5 ± 6.7
G1b: 25.7 ±4.1
G1c: 18.2 ± 4.8
Vineland maladaptive
behavior:
G1a: 27.0 ± 9.4
G1b: 19.8 ± 8.6
G1c: 28.3 ± 10.8
SIB-Q:
G1a: 32.7 ± 16.5
G1b: 17.5 ± 7.7
G1c: 36.2 ± 16.4
Y-BOCS, total score:
G1a: 11.5 ± 5.8
G1b: 27.8 ± 5.3
G1c: 14.8 ± 5.7
p = 0.005, G1 vs. baseline
Vineland maladaptive
behavior:
G1a: 13.8 ± 6.0
G1b: 20.2 ± 8.2
G1c: 19.5 ± 9.1
p = 0.0001, G1 vs. baseline
SIB-Q:
G1a: 15.5 ± 9.5
G1b: 18.8 ± 7.7
G1c: 20.2 ± 12.8
p = 0.0001, G1 vs. baseline
Quality considerations: no
comparison group; treatment
adherence not reported;
outcomes not coded by
masked assessors;
differences in concomitant
interventions not reported
Table 13. Key outcomes of studies assessing SRIs (continued)
Author, Year,
Country
Groups, N
Enrollment/N Final
Study Quality
Mean Age,
Years ± SD
Mean IQ ±
SD
Outcome Measure/
Baseline Scores, Mean ±
SD
Outcome Measure/Post-
Treatment Scores, Mean ±
SD
Quality Considerations
Brodkin et al.,69 1997
United States
G1: Clomipramine,
35/33
G1a: Responders, n =
18
G1b: Nonresponders,
n = 15
Quality: Poor
G1: 30.2 ± 7.0
G1: 64.6 ±
27.2
Y-BOCS, total score:
G1a: 18.7 ± 6.8
G1b: 17.9 ± 6.2
Y-BOCS, compulsion
subscale:
G1a: 13.7 ± 3.3
G1b: 13.9 ± 2.5
Y-BOCS, obsession
subscale:
G1a: 10 ± 6.8
G1b: 6.7 ± 6.2
Brown Aggression Scale:
G1a: 10.6 ± 7.4
G1b: 6.5 ± 4.1
Y-BOCS, total score:
G1a: 9.1 ± 3.0
G1b: 17.3 ± 7.8
p<0.001, G1 vs. baseline
p<0.001, G1a vs. G1b
Y-BOCS, compulsion
subscale:
G1a: 6.9 ± 2.1
G1b: 12.5 ± 3.3
p<0.001, G1 vs. baseline p<
0.001, G1a vs. G1b
Y-BOCS, obsession
subscale:
G1a: 4.4 ± 2.8
G1b: 8 ± 6.6
p<0.001, G1 vs. baseline
p<0.001, G1a vs. G1b
Brown Aggression Scale:
G1a: 3.7 ± 3.6
G1b: 6.4 ± 4.6
p<0.001, G1 vs. baseline
p<0.001, G1a vs. G1b
Quality considerations: no
comparison group; treatment
adherence not reported;
outcomes not coded by
masked assessors
McDougle et al.,52
1996
United States
G1: Fluvoxamine,
15/15
G2: Placebo, 15/15
Quality: Fair
G1: 30.1 ± 7.1
G2: 30.1 ± 8.4
G1: 82.5 ±
26.8
G2: 77.3 ±
33.1
Y-BOCS, total score:
G1: 21.4 ± 7.3
G2: 21.5 ± 6.8
Y-BOCS, total score:
G1: 13.7 ± 9.1
G2: 21.9 ± 6.7
p<.003, G1 vs. G2
Data for Vineland
Maladaptive Behavior and
Brown Aggression Scale
were not reported, although
statistically significant
improvements were noted.
Quality considerations:
randomization method not
clearly described; treatment
adherence not reported
Table 13. Key outcomes of studies assessing SRIs (continued)
Author, Year,
Country
Groups, N
Enrollment/N Final
Study Quality
Mean Age,
Years ± SD
Mean IQ ±
SD
Outcome Measure/
Baseline Scores, Mean ±
SD
Outcome Measure/Post-
Treatment Scores, Mean ±
SD
Quality Considerations
Cook et al.,71 1992
United States
G1: Fluoxetine, 23/23
Quality: Poor
15.9 ± 6.2
NR, 19 with
intellectual
disability
CGI-S, total:
5.7 ± 0.8
CGI-S, compulsion:
5.5 ± 1.5
CGI-S, total:
4.9 ± 1.1
p<0.002, G1 vs. baseline
CGI-S, compulsion:
4.7 ±1.6
p<0.005, G1 vs. baseline
Quality considerations: no
comparison group; inclusion
and exclusion criteria not
clearly stated; treatment
adherence not reported;
outcomes not coded by
masked assessors
ABC = Aberrant Behavior Checklist; ABC-I = Aberrant Behavior Checklist-Community Rating Scale-Irritability;
CARS = Childhood Autism Rating Scale; CGI-S = Clinical Global Impression-Severity; G = group; n = number; NR = not
reported; PDD-NOS = pervasive developmental disorder-not otherwise specified; SD = standard deviation; SIB-Q = Self-
Injurious Behavior Questionnaire; SRIs = serotonin reuptake inhibitors; Y-BOCS = Yale-Brown Obsessive Compulsive Scale
Medical Studies Reporting Harms
In one study of risperidone51 the authors describe sedation as the most prominent adverse
effect. Seven subjects did not complete the trial (three in the risperidone arm and four in the
placebo arm), with six subjects dropping out due to lack of improvement or agitation, and one
subject in the risperidone arm with abnormal gait. In another study of risperidone67the most
common adverse effects during the risperidone periods of the crossover phase were sedation and
gastrointestinal complaints. In 13 subjects these adverse effects triggered automatic 50 percent
dose reductions per the study protocol. The Dyskinesia Identification System Condensed User
Scale scores from the treatment phases were not statistically different when compared either with
the first placebo period (p = 0.052) or the second placebo period (p = 0.482). Symptoms on the
Neuroleptic Side Effects Checklist that were the most significant (p<0.001) with treatment
included drowsiness, weight gain, and increased appetite. Other symptoms were also significant
(p<0.05) including “too quiet,” “not themselves,” tremor, “lack of spontaneity,” and nasal
congestion. Mean weight gain during the entire study was 8.3 kg for adolescents and 6.0 kg for
adults. There were no abnormal laboratory tests.
In a study of haloperidol50 the mean duration of haloperidol treatment was 5.8 weeks with 23
of 33 (69.7%) subjects completing the 7-week treatment phase; seven of 10 subjects who
discontinued had adverse effects, including fatigue (n = 5), dystonia (n = 1), and depression (n =
1). The mean duration of placebo treatment was 5.4 weeks with 21 of 32 subjects (65.6%)
completing the 7-week phase; one of nine subjects who discontinued had adverse effects which
only included nose bleeds. The other eight subjects discontinued due to lack of improvement in
symptoms. There were no significant changes in 12-lead electrocardiogram variables, either in
the haloperidol or placebo phases.
In one study of opioid receptor antagonist identified,53 11 subjects were taking antipsychotics
with the dose held steady during the study. Possible adverse events included one subject with an
acute increase in self-injurious behavior, one subject with nausea and tiredness, and three
subjects with sedation. Liver function tests remained within normal ranges. The single dose had
no effect on the clinician-rated questionnaire, direct observation, self-injurious behavior, or
plasma beta-endorphins. Plasma cortisol was significantly increased (p = 0.006) for naltrexone
compared with placebo. Long-term treatment (4 weeks) with naltrexone resulted in a significant
increase in stereotypy as measured by the ABC stereotypy subscale.
One study of clomipramine50 used a crossover design with a mean duration of clomipramine
treatment of 4.5 weeks with 12 of 32 (37.5%) subjects completing the 7-week treatment phase;
12 of 12 subjects that discontinued had adverse effects which included fatigue or lethargy (n =
4), tremor (n = 2), tachycardia (n = 1), insomnia (n = 1), diaphoresis (n = 1), nausea or vomiting
(n = 1), decreased appetite (n = 1), and preexisting right bundle branch block (n = 1). The mean
duration of placebo treatment was 5.4 weeks with 21 of 32 (65.6%) subjects completing the 7-
week treatment phase; 1 of 9 subjects that discontinued had adverse effects which only included
nose bleeds (n = 1). There were no significant changes in 12-lead electrocardiogram variables,
either in the clomipramine or placebo arms. Statistical comparisons were not reported for the
clomipramine versus placebo for the CARS, Extrapyramidal Symptom Rating Scale, or Dosage
Treatment Emergent Symptom Scale.
Another study assessing the efficacy and tolerability of clomipramine reported adverse
effects in 13 individuals, 3 of whom had seizures during clomipramine treatment.69 Two of the
three participants with seizures had previously diagnosed seizure disorders and were
concurrently medicated with antiepileptic medication. The two participants not completing the
trial withdrew due to agitation in one individual and abdominal cramping in the second. Other
participants who completed the trial experienced constipation (n = 3), weight gain (n = 3),
anorgasmia (n = 1), and sedation (n = 2). There were no cardiovascular or extrapyramidal
adverse effects. There was no placebo control group to compare with the clomipramine treatment
group in this open-label trial.
One RCT52 investigated the efficacy of fluvoxamine in adults with autistic disorder. Adverse
effects in the fluvoxamine group included mild sedation (n = 2) and nausea (n = 3). There were
no significant changes in anticholinergic effects, vital signs, routine lab analyses, or
electrocardiogram.
In a case series68 assessing the efficacy and tolerability of sertraline, five subjects withdrew
from the study: three due to anxiety/agitation, one due to syncope, one due to noncompliance.
There were no cardiovascular, extrapyramidal, or seizure adverse effects. There was no placebo
control group for comparison of possible therapeutic effects or adverse events. Finally, another
case series71 examined fluoxetine and reported that six of 23 participants experienced side effects
that “significantly” interfered with function or outweighed therapeutic benefits. Harms reported
overall included agitation (n = 5), insomnia (n = 4), elated affect (n = 4), decreased appetite (n =
4), and increased screaming (n = 2). Additional harms were reported in at least one individual
(inappropriate behavior, crying, yawning, rash).
Studies of Allied Health Interventions
Key Points
• Five studies, one fair and four poor quality, investigated disparate allied health
approaches. Three studies included individuals with ASD and intellectual disability.
• A leisure/recreation program reported positive effects on stress and quality of life in a fair
quality RCT.
• Facilitated communication did not increase participants’ communication or literacy
abilities over their independent abilities.
• Some positive effects on social skills were reported in studies of music therapy, but
outcome measures were unvalidated and largely subjective.
• No two studies assessed the same intervention; therefore, although individual studies
report promising results, without replication, and with no studies of good quality, the
strength of evidence for the body of literature is insufficient that any allied health
approach is associated with positive outcomes.
Overview of the Literature
We identified five studies of allied health interventions49, 58-60, 70 including one fair quality
RCT investigating a leisure/recreation program.49 Appendix G provides the quality ratings for
each study. The RCT, conducted in Spain, included 71 individuals ranging from 17 to 49 years
of age with mean Leiter mental age scores of 64.36 ± 21.33 months in the intervention group and
61.44 ± 9.37 months in the control group. Assessments included measures of quality of life and
stress. Two poor quality prospective case series addressed facilitated communication,59, 70 and
two poor quality retrospective case series addressed music therapy.58, 60 Studies were conducted
in the United States58-60 and Canada70 and included participants ranging in age from 2 to 40
across the studies. The duration of treatment ranged from 20 hours to 7 months in three
studies;59, 60, 70 one study of music therapy reviewed data from participants who had participated
in varying hours of therapy.58 Studies of facilitated communication59, 70 employed outcome
measures gauging the number of correct responses to a given task with and without the aid of a
facilitator. Facilitators helped to steady or physically support the hand of an individual with ASD
either typing responses on a keyboard or pointing to images. Study evaluating a music therapy
program58, 60 reported on the number of goals met and social outcomes or social outcomes using
largely subjective measures. Tables 14 and 15 summarize key study outcomes.
Detailed Analysis
Allied Health Studies Addressing Core Symptoms of ASD
Music Therapy
A poor quality case series addressing music therapy58 used 2 years of therapist database
records to assess the number of goals met and types of music therapy employed with 40 clients.
Participants ages ranged from 2 to 49 years (mean age = 13.9) and all had diagnoses on the
autism spectrum. Diagnoses were not reported as confirmed within the study. Music therapy
involved individual or small or large group sessions and occurred in settings including a
community music school or group home. The number of sessions varied for each client.
Therapists assessed each client’s “level of difficulty” related to aggression, property
destruction, on-task behavior, and other domains on a scale with a maximum value of 14 points
(highest level of difficulty); participants’ level of difficulty ratings averaged 2.5. Therapists also
set and tracked goals met in areas including behavioral/psychosocial skills,
language/communication skills, perceptual/motor skills, and cognitive skills. Therapists defined
meeting a goal as an increase or decrease of 25 percent from a client’s baseline level of
performance. Parents also completed annual questionnaires to assess generalizations of skills to
other settings. All participants achieved their initial goal within 1 year as well as achieved 77
percent of intermediate goals. Attainment of goals was not affected by client level of difficulty or
session type. Thirty caregivers returned generalization surveys, which reported that all
participants used skills practiced in music therapy in nontherapy settings occasionally or
frequently.
Facilitated Communication
Two poor quality case series addressed facilitated communication,59, 70 and included 41
individuals with ASD ranging in age from 8 to 21. Both studies included individuals with limited
literacy, and one assessed the effects of facilitated communication via a series of picture
recognition tasks performed with and without a facilitator and with the facilitator informed and
uninformed of the object presented.70 Facilitators, staff members of a school for individuals with
autism, all received 2 days of facilitated communication training. In one task involving
participants’ pointing to the picture of a word displayed previously, the number of correct
responses was greatest when facilitators were aware of the word displayed. Facilitated
communication did not enhance participant performance beyond participants’ independent
communication abilities, and facilitator influence was evident for at least 12 of 20 participants. In
a second task using headphones and requiring responses to auditory cues, facilitators heard the
same message as participants, a different message, or white noise. Responses across all 3 trials
were not significantly different, and facilitator influence was evident for 14/20 participants.
In a third task participants completed segments of the Peabody Picture Vocabulary Test with
and without facilitated communication. Scores on the text did not differ significantly between
conditions; all 12 participants completing the test showed receptive language difficulties, and
there were no clear patterns of facilitator influence. The investigators also collected followup
data for seven participants after 5 to 7 additional months of facilitated communication use.
Additional time with facilitated communication did not increase participants’ accuracy of
responding and was associated with increased facilitator influence in one task (p<0.03).
A second case series addressing facilitated communication included 21 participants (mean
age = 15.5) with ASD and mild to profound intellectual disability and language development age
equivalent ranging from 1.6 to 5.1 years.59 Study tasks involved both facilitated and non-
facilitated communication. In the non-facilitated condition, facilitators were screened from
stimuli or investigator cues visible or audible to participants. Facilitators were trained in the
history and principles of facilitated communication for roughly 4 hours before participating in
the study, and facilitators unfamiliar to participants spent at least 2 weeks prior to the study
helping participants acclimate. Participants completed baseline measures without facilitation and
pretest measures with the assistance of screened facilitators. These tests were followed by 20
hours of facilitated communication exposure and training prior to completing post-test outcome
measures.
Investigators scored participant responses liberally, counting as correct partial words,
misspellings, and recognizable character strings embedded in other text (e.g., the characters
“OSY” were scored correctly for “yes”). Performance on initial test measures declined from
baseline (14/21 participants able to answer some questions correctly) to pretest (2/21 participants
able to answer some questions correctly). At post-test, conducted after facilitated communication
training and with screened facilitation, 2 of 21 participants were able to answer some questions
correctly. Scores for a test session during which facilitators were not screened were higher, with
6 out of 21 participants able to answer some questions correctly. No participants demonstrated
improved communication abilities or literacy.
Table 14. Key outcomes of studies of allied health interventions addressing core symptoms of
ASD
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Yrs, Mean ± SD
IQ, Mean ± SD
Key Outcomes
Music Therapy
Kaplan et al.,58 2005
United States
G1: Music therapy, 40/40
Quality: Poor
G1: 13.9 (range 2-49)
NR
• Retrospective review of client database records; music
therapists set goals and determined percentage
increase/decrease in skills/behavior relevant to goal.
• 40/40 participants with ASD met initial goals within 12
months of therapy; over 70% of participants met
intermediate goals.
• All caregivers returning generalization surveys (n = 30)
reported use of skills practiced in therapy sessions in
non-therapy sessions occasionally or frequently.
• Quality considerations: no comparison group;
systematic diagnostic approach not reported within
study; participants not clearly characterized (no
cognitive or developmental measures); attrition not
reported; intervention not fully described; measure of
treatment fidelity not reported; outcome measures not
valid/reliable; outcomes not coded by masked
assessors.
Facilitated Communication
Bebko et al.,70 1996
Canada
G1: Facilitated
communication
Quality: Poor
G1: 13 (range 6-21)
G1: 1.3 years - 4 years
(mental age range)
• 6 weeks of FC training and practice with up to 7months
followup data for 7 participants.
• Scores on visual stimulus experiment increased from
baseline when FC used and facilitator aware of word
being prompted (56.86% correct responses vs. 75%);
scores decreased from baseline when FC used and
facilitator not informed of word prompted (30% correct
responses vs.25.57%).
• Visual stimulus scores increased from baseline when
no FC used and facilitator was informed of word being
prompted (36.71% correct responses vs. 53.57%) and
decreased when no FC used and facilitator not
informed of word (35.71% correct vs. 32.57%).
• FC did not enhance communication beyond
participants’ independent abilities.
• Quality considerations: no comparison group; inclusion
and exclusion criteria not clearly stated; measure of
treatment fidelity not reported; differences in
concomitant interventions not reported; outcomes not
coded by masked assessors.
Table 14. Key outcomes of studies of allied health interventions addressing core symptoms of
ASD (continued)
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Yrs, Mean ± SD
IQ, Mean ± SD
Key Outcomes
Facilitated Communication (continued)
Eberlin et al.,59 1993
United States
G1: Facilitated
communication, 21/21
Quality: Poor
G1: 15.5 (range 11.3-20.2)
G1:
Mild to moderate
intellectual disability,
n = 2
Moderate to severe
intellectual disability,
n = 11
Severe to profound
intellectual disability,
n = 8
• 20 total hours FC training.
• Median correct answers declined from baseline (no
FC) after testing using FC with facilitator not. informed
of words prompted (8 correct answers vs. 0); median
score at testing with FC and facilitator informed of word
prompted = 1.
• Communication ability or literacy did not improve for
any participants.
• Quality considerations: no comparison group;
differences in concomitant interventions not reported;
outcomes not coded by masked assessors.
ASD = autism spectrum disorders; FC = facilitated communication; G = group; IQ = intelligence quotient; N = number;
SD = standard deviation
Allied Health Studies Addressing Independent Functioning
One fair quality RCT investigating a leisure/recreation program randomized individuals with
ASD to either a waiting list control group (n = 34) or a 12-month leisure program emphasizing
engagement in exercise, playing games and completing crafts, interacting with media, and
attending social events (n = 37) (Table 15).49 ASD diagnoses were confirmed within the study.
Participants ranged in age from 17 to 49 years and had mean Leiter mental age scores of 64.36 ±
21.33 months in the intervention group and 61.44 ± 9.37 months in the control group.
Assessments included measures of quality of life and stress completed at baseline and after 12
months by participants with adequate verbal skills or by individuals familiar with the participant.
Scores on the stress assessment improved for individuals in the intervention group compared
with those in the control group (p<0.001). Overall quality of life scores similarly improved for
intervention participants compared with the waiting list group; however, scores on
empowerment/independence and social/integration subscales did not improve significantly
between groups.
One poor quality case series investigated music therapy interventions using largely subjective
measures. One study addressed a university-based program aimed at assessing the feasibility of a
music program in promoting social skills in adolescents and young adults with ASD.60 The 22
participants ranged from age 13 to 29 (mean = 18), and diagnoses were not reported as
confirmed within the study. The program’s curriculum included sessions in learning about music,
music appreciation, video production, and storytelling with music over 8 weeks. Investigators
assessed participants’ and parents’ impressions of social benefits gained via a 1 (low) to 10
(high) scale and open-ended questions. Both parents and participants rated the program highly
with mean scores of nearly 7. Nineteen participants indicated that they had made friends during
the program, and 11 parents noted that their children had made friends.
Table 15. Summary of outcomes of studies of allied health interventions addressing independent
functioning
Author, Year, Country
Groups, N Enrollment/N
Final
Study Quality
Age, Yrs, Mean ± SD
IQ, Mean ± SD
Key Outcomes
Garcia-Villamisar et al.,49
2010
Spain
G1: Leisure/recreation
program, 37/37
G2: Wait list control,
34/34
Quality: Fair
G1: 31.49 ± 4.83
G2: 30.06 ± 3.44
IQ (Leiter)
G1: 63.46 ± 21.33
G2: 61.44 ± 9.37
• Participants randomized to 12-month recreation/leisure
program or waiting list.
• Stress and total quality of life scores improved for
treatment group compared with wait list group
(p<0.001).
• Scores on empowerment/independence and
social/integration subscale improved for treatment
group vs. control but not significantly.
• Quality considerations: randomization method not
clearly described; attrition not reported; measure of
treatment fidelity not reported; differences in
concomitant interventions not reported.
Greher et al.,60 2010
United States
G1: Music therapy
(SoundScape), 22/22
Quality: Poor
G1: 18 (range: 13-29)
NR
• 8-week program emphasizing understanding elements
of music and recording music.
• Participants and parents rated social benefits of
program highly.
• 11 participants and 19 parents reported that they/their
child had developed friendships through the program.
• Quality considerations: no comparison group;
systematic diagnostic approach not reported within
study; participants not clearly characterized (no
cognitive or developmental measures); measure of
treatment fidelity not reported; differences in
concomitant interventions not reported; outcomes not
coded by masked assessors.
G = group; IQ = intelligence quotient; N = number; NR = not reported; SD = standard deviation
Discussion
State of the Literature
Despite a growing population of adolescents and young adults who have diagnoses of an
autism spectrum disorder (ASD) and the need for effective intervention across the lifespan, very
little research is available to guide therapy in adolescents and young adults with ASD. The
available research is lacking in scientific rigor. We identified 32 studies (one paper reported two
separate studies), of which 10 were randomized controlled trials (RCTs). Nonetheless, most
studies were of poor quality; only five were fair quality and none was good quality.
Studies typically addressed the core symptoms (impairments in communication, social
interaction, or behavior) of ASD (Key Question 1) and the effects of interventions on functional
and adaptive behavior (Key Question 3). One study addressed the transition process (Key
Question 4), and two addressed family outcomes (Key Question 6). Harms of interventions (Key
question 5) were only discussed in studies of medical approaches. Eight studies of medical
approaches and one behavioral study addressed Key Question 2, which examined the effects of
interventions on comorbid medical or mental health conditions (e.g., epilepsy, sleep disorders,
motor impairments, obesity, depression, anxiety, acute and episodic aggression, attention deficit
hyperactivity disorder, etc.).
Summary of Outcomes
Studies of Behavioral Interventions
Six poor quality studies of targeted social skills interventions representing different
individual/group- and computer-based paradigms met our inclusion criteria.47, 61-63, 76, 77 Research
involving individual or group-based interventions61, 62, 76, 77 reported improvements across a
variety of social skills as rated by parents. Research on computer assisted interventions suggested
improvements associated with emotion recognition.47, 63 However, each study employed a
different approach and paradigm, making synthesis of the results into one estimate of effect
impossible. Likewise, such social skills interventions have yet to demonstrate consistent
generalization of skills across settings and often circumscribe interventions to individuals with
average to above average verbal and/or cognitive abilities. As such, the strength of evidence for
social skills interventions is insufficient, meaning that future research is needed to establish one
effect.
A single poor quality case series of a semi-residential, intensive behavior-based intervention
included 34 adolescents and focused on changes in adaptive behavior after 2 years of program
attendance.64 Overall, both male and female participants improved on measures of socialization,
and females also improved in daily living and motor skills While the authors reported that there
was a positive impact across a fairly heterogeneous group, the study did not involve a control
group and did not clearly define an intervention; parental satisfaction data reported were positive.
Studies of Educational Interventions
Research into language and communication strategies for adolescents and young adults with
ASD is very limited, with only two small crossover studies identified in this population. There is
little evidence to support selection among various educational strategies, with one study finding
similar vocabulary acquisition between analog and natural language approaches.66 Procedural
facilitation and anaphoric cuing showed some promise for increasing vocabulary in high-
functioning ASD but were addressed in only one small, short term study.65
Studies of Adaptive/Life Skills Interventions
Studies of adaptive-focused interventions meeting our criteria were of poor quality,
addressed disparate interventions, and included few participants. No study included more than 81
individuals with ASD, and at least two studies included individuals with concomitant intellectual
disability. Interventions addressing teaching self-care skills (shoe lacing),55 digital memory
aids,57 and a residential, Treatment and Education of Autistic and Communication related
handicapped Children (TEACCH)-based program54 reported some positive effects. Studies were
typically uncontrolled and of short duration, however.
One poor quality study assessed the effects of a classroom rotation schedule on crisis events
in a residential school56 and reported no significant increase in events after the implementation of
classroom rotation. The few studies addressing family-focused outcomes reported parent or
family satisfaction with treatment approaches. One study of a TEACCH-based residential
program compared with group homes and institutions reported greater satisfaction with treatment
and program participants’ community involvement among parents of individuals in the
TEACCH-based facility compared with group homes.54 Parents of individuals in the TEACCH
residence were also more satisfied with the impact of the placement on the family than parents of
individuals in other groups. Assignment to the TEACCH program, however, was not random;
thus individuals in the group may have differed meaningfully from individuals in group homes,
family homes, or institutions.
Studies of Vocational Interventions
Our search identified five studies focused on supported employment/vocational
interventions.17, 48, 72-75 It is important to note that all of the identified studies focused on on-the-
job supports as the employment/vocational intervention; no other vocational interventions were
reported in the literature meeting our study criteria. Our ability to assess the benefit of supported
employment programs is limited, given the existing research. No study utilized random
assignment, making it difficult to draw conclusions about the effectiveness of the programs. The
majority of the studies were small, and all were poor quality thus the strength of the evidence is
insufficient at this time.
Supported employment interventions are particularly understudied. For example, only one
study examined rates of employment for programs that lasted 3 years or longer.17 Further, this
longer-term study did not include a control group, making it impossible to determine the rates of
employment over time for young adults with ASD who were not participating in the supported
employment intervention. Finally, none of the studies examined whether increased employment
rates or improvements in other outcomes were sustained after the termination of the supported
employment intervention.
Studies of Medical Interventions
The use of medical interventions in adolescents and young adults with ASD is common.78
However, there is little evidence that supports the use of medical interventions specifically in this
population. We identified three studies of antipsychotic medications,50, 51, 67 five studies of
serotonin reuptake inhibitors (SRIs),50, 52, 68, 69, 71 and one study of an opiate antagonist.53 Overall,
most of these studies focused on the use of medications to address specific challenging behaviors
(i.e., aggression or irritability). Four studies were fair quality,50-53 and four were poor.67-69, 71
The most consistent findings were identified for antipsychotic medications. An RCT studying
risperidone found improvements in aggression, repetitive behavior, sensory motor behaviors, and
overall behavioral symptoms.51 A crossover study of risperidone also showed a significant
reduction of irritability/agitation ratings with risperidone treatment, but the control was
indirect.67 A placebo-controlled crossover study found that haloperidol significantly improved
hyperactivity/defiance ratings, but no significant difference was found for irritability/agitation or
other symptoms.50 While limited literature supports the use of risperidone in adolescents or
young adults with ASD, the efficacy of risperidone in studies including mostly children has
moderate strength of evidence32 that is consistent with the results of the one fair RCT and one
poor crossover study in adults with ASD. There is therefore no evidence to suggest that the
effects of risperidone for irritability/agitation in ASD is specific to a particular age range.
A number of studies of SRIs were identified but with limited consistency across studies as a
whole. An RCT of fluvoxamine showed decreases in repetitive behavior, aggression, autistic
symptoms, and language usage.52 In contrast, no significant differences were observed in a
crossover study of clomipramine versus placebo.50 Three case series of SRIs were also identified,
including sertraline, fluoxetine, and clomipramine, with each study reporting some benefit to
treatment.68, 69, 71 A recent study not meeting criteria for this review contributes to the limited
data on SRIs: the placebo-controlled RCT79 of fluoxetine included 37 individuals with ASD with
a mean age of 34.31 and reported improvements in repetitive behavior and ASD symptoms in the
treatment group and mild harms. This study used a different medication than the one fair quality
study in our age range, so it would be unlikely to influence the strength of evidence for a specific
medication. It is possible, however, that a systematic review of SRIs in the broader age range of
adults with ASD could provide data that might increase our confidence in the effect.
A crossover study of the opioid receptor antagonist naltrexone found no significant
improvements in problem behavior and showed worsening of stereotyped behavior with
naltrexone treatment compared with placebo.53
Based upon the published studies in adolescents and adults with ASD, the strength of
evidence is insufficient regarding harms associated with medications tested in this population. As
in the case of efficacy, the data on adverse effects associated with risperidone, including sedation
and weight gain, are consistent with the high strength of evidence for the association of treatment
with these adverse effects in children with ASD.32 The available evidence therefore appears
consistent in supporting our understanding of the risk of these adverse events in ASD without
being limited to a specific age range. Of course, this does not mean that other medications tested
in ASD are free of adverse effects. It is reasonable to expect that, in contrast to efficacy, which is
more likely to be specific to disorder and symptom, adverse effects are more likely to extend
across diverse groups of subjects studied. Clinicians evaluating the evidence and sharing
information with families routinely take this perspective, as does the Food and Drug
Administration in mandating that all adverse events be listed for a drug, rather than just those for
a particular indication.
As one example, the limited studies of adults with ASD treated with risperidone indicate
weight gain as an adverse effect but in too few studies to draw a clear conclusion about the
strength of evidence. There is, however, high strength of evidence for weight gain in children
with ASD treated with risperidone, as noted in a previous comparative effectiveness review.32
Similarly, recent Cochrane reviews found substantial evidence for weight gain in adults with
schizophrenia or bipolar disorder treated with risperidone.80,81 When the broader evidence base is
considered, the consistency of these findings supports an association of weight gain with
risperidone in adults with ASD, just as is true in children with ASD and adults with other
disorders. This approach to assessing the evidence for harms is outside of the scope of this
review, but similar conclusions could be drawn with respect to sedation and extrapyramidal
symptoms with risperidone or haloperidol.
Studies of Allied Health Interventions
Few studies of allied health interventions met our criteria.49, 58-60, 70 One fair quality RCT
assessed a 12-month recreation program49 and reported improved quality of life and lower stress
scores in individuals participating in the leisure/recreation program compared with those on a
waiting list. One poor quality case series60 included 22 young adults engaged in a music therapy
intervention. Nearly all participants reported making friends during the program and were
generally satisfied with the program. Both studies assessed outcomes shortly after treatment, so
longer-term effects of the interventions are not known.
Two studies of facilitated communication59,70 used approaches designed to assess the effects
of facilitation both with and without facilitators’ awareness of the word being prompted. Both
studies demonstrated some facilitator influence and limited effects on participants’ independent
ability to communicate. One retrospective study of a music therapy program reported some
positive effects on participants’ social skills using largely subjective outcome measures.58
Strength of the Evidence for Effectiveness of Therapies
Overview
We assessed the literature by considering both the observed effectiveness of interventions
and the confidence that we have in the stability of those effects in the face of future research. The
degree of confidence that the observed effect of an intervention is unlikely to change is presented
as strength of evidence and can be insufficient, low, moderate or high. Strength of evidence
describes the adequacy of the current research, both quantity and quality, and whether the entire
body of current research provides a consistent and precise estimate of effect. Interventions that
have shown significant benefit in a small number of studies but have not yet been replicated
using rigorous study designs will have insufficient or low strength of evidence, despite
potentially offering clinically important benefits. Future research may find that the intervention
is either effective or ineffective.
Methods for applying strength of evidence assessments are established in the Effective
Health Care Program’s Methods Guide for Effectiveness and Comparative Effectiveness
Reviews46 and are based on consideration of four domains: risk of bias, consistency in direction
of the effect, directness in measuring intended outcomes, and precision of effect. Table 3 in the
Methods section of the report includes a description of these domains.
We determined the strength of evidence for outcomes including social skills, adaptive
behavior, autism symptom, challenging and repetitive behavior, harms of treatment,
employment, and parent satisfaction. Tables 16 through 21 document the strength of evidence for
each domain of the major intervention-outcome combinations.
Strength of the Evidence
Behavioral Interventions
All studies assessing behavioral interventions were poor quality. The strength of the evidence
for all interventions targeting social skills is insufficient as it is for an intensive behavioral
intervention (Table 16).
Table 16. Intervention, strength of evidence domains, and strength of evidence for outcomes of
behavioral studies
Outcome/Intervention
Study
Type (N
Studies of
Type
Reporting
Outcome)
Domains Pertaining to Strength of Evidence (SOE)
SOE
Risk of
Bias
Consistency
Directness
Precision
Adaptive Behavior
Intensive behavioral
treatment
Case series
(1)64
High
Unknown
Direct
Imprecise
Insufficient
Problem Behavior
Social skills
individual/group training
Case series
(1)77
High
Unknown
Direct
Imprecise
Insufficient
Social Skills/Social Behaviors
Social Skils groups
RCT (1)61
Case series
(1)62
High
Consistent
Direct
Imprecise
Insufficient
Computer-based social
skills interventiona
RCT (3)47, 63
nRCT (1)47
Medium
Inconsistent
Indirect
Imprecise
Insufficient
Parent Satisfaction
Intensive behavioral
treatment
Case series
(1)64
High
Unknown
Direct
Imprecise
Insufficient
N = number; RCT = randomized controlled trial; SOE = strength of evidence
aPaper includes two unique studies reported in one publication.
Educational Interventions
Only two poor quality studies investigated educational interventions targeting
communication skills thus we assessed the strength of the evidence as insufficient (Table 17).
Table 17. Intervention, strength of evidence domains, and strength of evidence for key outcomes
of educational studies
Outcome/Intervention
Study
Type (N
Studies of
Type
Reporting
Outcome)
Domains Pertaining to Strength of Evidence (SOE)
SOE
Risk of
Bias
Consistency
Directness
Precision
Language/Communication
Teaching strategies
RCT (1)65
nRCT (1)66
High
Inconsistent
Direct
Imprecise
Insufficient
N = number; nRCT = nonrandomized controlled trial; RCT = randomized controlled trial; SOE = strength of evidence
Adaptive/Life Skills Interventions
With four poor quality studies targeting disparate outcomes using disparate adaptive/life
skills-focused interventions focused on highly specific tasks/skills, we rated the strength of the
evidence overall as insufficient (Table 18).
Table 18. Intervention, strength of evidence domains, and strength of evidence for outcomes of
adaptive/life skills studies
Outcome/Intervention
Study
Type (N
Studies of
Type
Reporting
Outcome)
Domains Pertaining to Strength of Evidence (SOE)
SOE
Risk of
Bias
Consistency
Directness
Precision
Adaptive/Functional Behavior
Self-care/ADL training
RCT (1)55
Prospective
cohort (1)54
Case series
(2)56, 57
High
Consistent
Direct
Imprecise
Insufficient
Parent Satisfaction
TEACCH-based program
Prospective
cohort (1)54
High
Unknown
Direct
Imprecise
Insufficient
ADL = activities of daily living; N = number; RCT = randomized controlled trial; SOE = strength of evidence;
TEACCH = Treatment and Education of Autistic and Communication related Handicapped Children
Vocational Interventions
Five studies assessed employment-related outcomes as well as outcomes related to
cognition and autism symptoms. All studies were poor quality, and we assessed the strength of
the evidence as insufficient for all outcomes (Table 19).
Table 19. Intervention, strength of evidence domains, and strength of evidence for supported
employment/vocational interventions
Outcome/Intervention
Study
Type
(N Studies
of Type
Reporting
Outcome)
Domains Pertaining to Strength of Evidence (SOE)
SOE
Risk of
Bias
Consistency
Directness
Precision
Employment
Supported employment/
vocational
Prospective
cohort (1)73
Case series
(1)17
Cross-
sectional
(1)48
High
Consistent
Direct
Imprecise
Insufficient
Autism Symptoms
Supported employment/
vocational
nRCT (1)74,
75
High
Unknown
Direct
Imprecise
Insufficient
Quality of Life
Supported employment/
vocational
nRCT (1)74,
75
High
Unknown
Direct
Imprecise
Insufficient
Cognitive Development
Supported employment/
vocational
nRCT (1)72
Prospective
cohort
High
Unknown
Direct
Imprecise
Insufficient
N = number; nRCT = nonrandomized controlled trial; SOE = strength of evidence
Medical Interventions
There were no good studies identified for antipsychotics, serotonin reuptake inhibitors, or
opioid receptor antagonists in adolescents or young adults with ASD. The strength of evidence
for each of these medication classes is insufficient. Similarly the strength of evidence for adverse
effects is also insufficient (Table 20).
The strength of evidence for the use of risperidone to treat irritability and repetitive behaviors
in ASD is insufficient based on a single fair RCT 51 and a single poor crossover study.67 The
strength of evidence for the use of haloperidol to treat hyperactivity/defiance in ASD is
insufficient based on a single fair study.50 The strength of evidence for the use of naltrexone for
the treatment of either problem behaviors or core ASD symptoms is insufficient based on a
single fair crossover trial. The strength of evidence for the use of clomipramine for the treatment
of ASD symptoms is insufficient based on a single fair study,50 and a single poor case series
study.69 The strength of evidence for the use of fluvoxamine for repetitive behaviors, aggression,
or other ASD symptoms is insufficient based on a single fair RCT.52
Table 20. Intervention, strength of evidence domains, and strength of evidence for outcomes of
medical studies
Outcome/Intervention
Study
Type
(N Studies
of Type
Reporting
Outcome)
Domains Pertaining to Strength of Evidence (SOE)
SOE
Risk of
Bias
Consistency
Directness
Precision
Challenging Behavior
Risperidone
RCT (2)51, 67
Medium
Consistent
Direct
Imprecise
Insufficient
Haloperidol
RCT (1)50
Medium
Unknown
Direct
Imprecise
Insufficient
Clomipramine
RCT (1)50
Case series
(1) 69
Medium
Inconsistent
Direct
Imprecise
Insufficient
Fluvoxamine
RCT (1)52
Medium
Unknown
Direct
Imprecise
Insufficient
Sertraline
Case series
(1)68
High
Unknown
Direct
Imprecise
Insufficient
Repetitive Behavior
Risperidone
RCT (1)51
Medium
Consistent
Direct
Imprecise
Insufficient
Naltrexone
RCT (1)53
Medium
Unknown
Direct
Imprecise
Insufficient
Haloperidol
RCT (1)50
Medium
Unknown
Direct
Imprecise
Insufficient
Clomipramine
RCT (1)50
Case series
(1)69
Medium
Inconsistent
Direct
Imprecise
Insufficient
Sertraline
Case series
(1)68
High
Unknown
Direct
Imprecise
Insufficient
Fluoxetine
Case series
(1)71
High
Unknown
Indirect
Imprecise
Insufficient
Harms
Risperidone
RCT (2)51, 67
Medium
Consistent
Direct
Imprecise
Insufficient
Naltrexone
RCT (1)53
Medium
Unknown
Direct
Imprecise
Insufficient
Haloperidol
Case series
(1)68
Medium
Unknown
Direct
Imprecise
Insufficient
Clomipramine
RCT (1)50
Case series
(1)69
Medium
Inconsistent
Direct
Imprecise
Insufficient
Sertraline
Case series
(1)68
High
Unknown
Direct
Imprecise
Insufficient
Fluoxetine
Case series
(1)71
High
Unknown
Indirect
Imprecise
Insufficient
Fluvoxamine
RCT (1)52
Medium
Unknown
Direct
Imprecise
Insufficient
N = number; RCT = randomized controlled trial; SOE = strength of evidence
Allied Health Interventions
With only one fair quality RCT of a leisure program addressing quality of life outcomes, we
rated the strength of the evidence as insufficient for this outcome. Similarly, the strength of the
evidence was insufficient for other allied health interventions and outcomes (Table 21).
Table 21. Intervention, strength of evidence domains, and strength of evidence for outcomes of
allied health studies
Outcome/Intervention
Study
Type (N
Studies of
Type
Reporting
Outcome)
Domains Pertaining to Strength of Evidence (SOE)
SOE
Risk of
Bias
Consistency
Directness
Precision
Quality of Life
Recreation program
RCT (1)49
High
Unknown
Direct
Imprecise
Insufficient
Social Skills/Social Behaviors
Music therapy
Case series
(1)60
High
Unknown
Indirect
Imprecise
Insufficient
Language
Music therapy
Case series
(1)58
High
Unknown
Indirect
Imprecise
Insufficient
Facilitated
communication
Case series
(2)59, 70
High
Consistent
Direct
Imprecise
Insufficient
N = number; RCT = randomized controlled trial; SOE = strength of evidence
Applicability
Applicability of the Evidence
By definition, ASDs are heterogeneous. Characterizing a “typical” individual with an ASD is
not possible, although certain symptoms are central to the range of individuals within the autism
spectrum. Individual therapies are developed and tested to ameliorate specific symptoms or
groups of symptoms, often in a fairly circumscribed subset of children. We describe the
applicability of the evidence for interventions represented in this review below.
Behavioral Interventions
Studies of behavioral interventions to date have been limited in scope. The single
investigation of an intensive, comprehensive behavioral intervention was conducted across a
broad age range of individuals (4 to 18) within a residential rehabilitation center. While
numerous studies of younger children have focused on intensive behavioral and developmental
interventions, quite often behavioral interventions for adolescents and young adults with ASD
have been limited to social skills interventions. Social skills interventions in turn have been
limited to investigations conducted with individuals with substantial cognitive and verbal
abilities, often individuals with high-functioning autism or Asperger syndrome. Therefore the
evidence of social skills interventions is likely applicable only to older, higher functioning
individuals. The range of approaches studied also does not always match what is available in
practice—that is, either the studies were conducted in highly controlled environments (e.g.,
university-supported manualized intervention trials), the actual methodology was not well
described (i.e., approaches lacking treatment manuals), or the computer based intervention is not
widely available. Thus, individuals wishing to infer the potential results of clinical practice based
on the available research need to assess carefully the degree to which the study methods matched
those available and used in practice. Ultimately, the effectiveness of social skills interventions
within and outside of these limited samples and setting is currently unknown.
Educational Interventions
The two studies of educational interventions included in this review were conducted in the
United States and Canada in the home and educational environments. Characteristics of
participants in the studies (intelligence quotient [IQ], language skills) likely represented a wide
spectrum and were not categorized well enough to assess their applicability to the larger
population. Educational approaches targeted acquisition of vocabulary and included individual-
and group-based strategies; the intensity of interventions varied from a single session to multiple
sessions across several weeks. Outcomes examined in this literature primarily focused on reading
comprehension and acquisition of vocabulary among individuals exposed to various teaching
approaches.
Adaptive/Life Skills Interventions
Two adaptive/life skills studies explicitly included individuals with ASD and intellectual
disability,54, 55 however specific measures of developmental and behavioral profiles of included
individuals were quite variable and often lacked adequate description across studies. One study
explicitly included high school students able to use a computer and program a digital device,57
but specific cognitive and behavioral characteristics of this group were not well described. The
remaining study included individuals attending a special school and likewise did not report
explicit standardized measurements of the developmental and behavioral characteristics of the
group apart from ASD diagnosis.56
Studies of certain adaptive/life skills interventions based on intensive application of highly
specified programs focused on individuals with ASD with profound cognitive impairments,
while specific technological and educational structure-related interventions targeted individuals
with cognitive abilities closer to developmental expectations. However, given the variability and
limited information concerning developmental, cognitive, and behavioral characteristics of study
populations in this category, it is unclear how findings from these studies might apply across
varying individuals with ASD. Furthermore, given methodological limitations in study design
and time frame, it is not only unclear how adaptive/life skills interventions apply to varying
groups of individuals, but it is unclear whether they represent intervention enhancements with
meaningful effect over time.
Vocational Interventions
Although often not well characterized, the populations from studies examining the efficacy
of supported employment/vocational interventions likely represent higher-functioning adults
with ASD. Studies were conducted in the United States, United Kingdom, Spain, and Germany,
and two specifically targeted adults with high-functioning autism or Asperger syndrome. One
study included those who had nonverbal IQ scores above the 35th percentile. Although a fourth
study included adults with a range of intellectual functioning, all adults were required to have
“acceptable professional and vocational abilities.” The final study did not report on the
intellectual functioning of the sample.
Supported work interventions ranged in duration from 2 years to 8 years, and included job
finding services and job coaches who accompanied adults with ASD to the worksite.
Comparators included adults in a sheltered work setting (i.e., sheltered workshop) as well as
adults who were receiving no supported employment services. The most common outcome
assessed was the presence/absence of a job in the community. Other aspects of employment that
were sometimes examined included the length of time employed, number of hours working per
week, and wages. One study each assessed autism symptoms, quality of life, and cognitive
functioning. Overall, participants in these studies were drawn from the community and thus
reflect characteristics of the larger population of higher functioning individuals. Interventions
also took place within the larger community. Jobs located were typically support or service
positions and do not reflect the scope of employment possibilities potentially available for
individuals with ASD with more developed cognitive abilities or social and communication
skills.
Medical Interventions
Studies of Antipsychotics
Three RCTs, including mostly adolescents and young adults (age 13 to 30 years) but not
limited to this range, examined antipsychotics. Although the mean age was within this range the
populations include younger children and older adults. All of the studies used Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria-based diagnoses of
autistic disorder as an inclusion criterion. One risperidone study also included individuals with
pervasive developmental disorder-not otherwise specified (PDD-NOS). Inclusion criteria for the
two risperidone studies also included a minimum level of problem behaviors. The mean IQ of the
patients was in the range of intellectual disability in the two risperidone studies, while the
haloperidol study did not report IQ. Doses of risperidone or haloperidol in all three RCTs were
within the range of doses used clinically for some adolescents and young adults with ASD.
All three RCTs assessed aggressive behavior, repetitive behaviors, and general autism
symptoms. All of the studies monitored for adverse effects (extrapyramidal and others) either
clinically or with specific assessments. Some, but not all, of the studies specifically assessed
repetitive behaviors, self-injurious behavior, social relationships, or language. All three of these
RCTs were conducted in academic clinic settings in the United States and Canada. The
characteristics of these settings may limit applicability.
Studies of Opioid Receptor Antagonists
One placebo-controlled RCT assessed naltrexone and included adult subjects with Diagnostic
and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) criteria-based
diagnoses of autistic disorder. Participants also reportedly had intellectual disabilities.
Naltrexone dose in one cohort was 50 mg/day but in the second cohort was increased to 150
mg/day. The increased dose was slightly higher than other studies cited, and the clinical
applicability of these doses to patients with ASD has not been established.
The primary outcome was self-injurious behavior. Additional outcomes included irritability,
stereotypy, hyperactivity, inappropriate speech, social withdrawal, and global clinical
improvement. This RCT was conducted in an academic clinic setting in the Netherlands, and the
applicability may be limited by this setting.
Studies of SRIs
Five studies (two placebo-controlled RCTs and four case series) investigated SRIs including
clomipramine, fluvoxamine, sertraline, and fluoxetine. All participants had DSM-IV or DSM-III-
R criteria-based diagnoses of autistic disorder. Two of studies also included other types of ASD
(e.g., PDD-NOS and Asperger syndrome). Most of the subjects in these studies were adolescents
and young adults (ages 13 to 30 years). The mean age was within this range, although some
younger children and older adults were included. Drug dosages used in these studies were
consistent with doses used clinically for some adolescents and young adults; however, the
clinical applicability of these doses to patients with ASD has not been established.
Most of the studies assessed repetitive behaviors, aggressive behavior, and general autism
symptoms. Some, but not all of the studies specifically assessed self-injurious behavior, social
relationships, or language. All studies were conducted in academic clinic settings in the United
States and Canada. The applicability of these studies may be limited by these settings.
Allied Health Interventions
The five studies49, 58-60, 70 of allied health interventions meeting our criteria included disparate
groups of individuals and interventions. Three of the studies explicitly included individuals with
intellectual disability,49, 59, 70 and participant ages ranged widely, though most were in the
adolescent range. With the exception of an RCT of a recreation program49 employing a waiting
list control condition, studies were case series and thus lacked comparison groups. In studies of
facilitated communication, all participants engaged in communication trials in which the
facilitator was either aware or not aware of the word or image being prompted. Outcomes
included quality of life and stress level in the recreation program RCT, socials skills-related
outcomes in studies of music therapy, and language/vocabulary in studies of facilitated
communication. Interventions occurred in university-based or specialized developmental
disabilities treatment centers and may not be widely available to the larger community with
ASD. Studies were short term with the exception of the recreation program RCT,49 which
assessed individuals after 12 months of participation.
Gaps in the Evidence
Methodologic Considerations
A number of methodologic considerations may be helpful for understanding the current state
of the literature and for guiding future research. Of the 32 studies included in the report, 18 used
a comparison group. Of those, 11 applied random assignment, and of those 11, 3 were assessed
to have randomized appropriately. The rest of the studies were case series or cross-sectional. Few
studies in this area are prospective trials, most being retrospective program evaluations, which
have substantial risks of bias.
Growth in the number of studies with greater attention to rigorous design for the purpose of
studying effectiveness will provide additional information for those making decisions about care
in the future. Over half (18 of 32) of the studies reported use of an adequate diagnostic approach,
and we suggest that future research attend to improved reporting about the basis for diagnosis of
individuals included in the studies. Most, but not all (26 of 32) fully described inclusion and
exclusion criteria, which is helpful for characterizing the population and assessing the
applicability of the evidence. Reporting of either fidelity (for behavioral studies) or treatment
adherence was low, with eight studies reporting fidelity and five studies reporting adherence.
Again, this information is important to end users of the research for assessing applicability and
understanding the implications of the results.
Methodologic strengths in this literature included the use of valid outcomes measures (29 of
32 studies), appropriate sources (e.g., teacher or parent report) of outcome data (31 of 32
studies), and appropriate statistical analysis (26 of 32) for the study design.
Future Research
The period of development representing the transition from adolescence to early adulthood
presents numerous challenges for individuals with and without neurodevelopmental challenges.
During this same interval individuals with ASD are presented with additional complexities that
require efforts to maximize the possibility of a positive transition and achievement of individual
goals for independence. Nonetheless, and despite increasing numbers of adolescents facing this
transition, no area of research provides sufficient strength of evidence for the impact of specific
intervention strategies in terms of improving important outcomes for specific groups of
individuals with ASD.
Overall, there is a dearth of evidence in all areas of care for adolescents and young adults
with ASD, and it is urgent that more rigorous studies be developed and conducted. It is unlikely
that large scale implementation of interventions will be considered until a stronger evidence base
is developed, despite growing numbers of individuals with need, and some small studies
demonstrating initial promise. A fruitful area for consideration may be identifying
programs/interventions that are appropriate candidates for developing treatment manuals to
encourage standardized replication of promising approaches.
Basic understanding of the effects of aging on health, cognitive skills and other domains of
functioning is absent, and evaluations of interventions are rare. The lack of randomized,
controlled trials is notable in all categories of intervention, but especially so in medical
interventions, where substantial adverse events may be associated with medication use in
adolescence. Only three studies reported more than 12 months of followup 17, 54, 74; longer term
data are needed in all areas of therapy. Furthermore, although early intervention for individuals
with ASD is often delivered in the home or at specialized agencies, behavioral and educational
interventions for adolescents and adults with ASD are likely to take place in existing community-
based settings such as schools and businesses, with non-specialists having a key role in
implementation. Thus, another critical issue is to design interventions for implementation in such
settings.
The behavioral literature generally focuses on subsets of individuals with ASD, often those
who are higher functioning, and may not be representative of the range of individuals with ASD.
In particular, more attention is warranted to understanding the impact of behavioral interventions
in the lives of individuals and how these interventions generalize to real-world impact and
outcome. Few studies addressing educational interventions in the adolescent and young adult
population have been conducted, and studies focusing on life skills or adaptive behaviors have
included few individuals in typically short-term studies focused on very specific short-term
intermediate outcomes. More research in both areas over a broader time frame with more clearly
defined populations is critical for helping individuals with ASD transition to greater
independence.
In vocational research, studies are needed that illuminate which aspects of multifaceted
supported employment programs have the greatest impact. Studies that do show evidence of
effectiveness in this area should collect longer-term data to describe the degree to which
findings, including the duration of employment, continue after the intervention itself is removed.
These studies should also broaden the outcomes measured, to include other functional outcomes
such as quality of life, educational attainment, residential outcomes and social outcomes.
Similarly, allied health studies are needed to understand best approaches to fostering independent
living skills and ways in which improvements in motor skills may affect communication and
other domains.
Medical studies conducted in adolescents and young adults have focused largely on problem
behaviors, and additional data are needed on medical comorbidities in adolescents with ASD.
Clear evidence from earlier studies of antipsychotics, which included mostly younger children,
supports the use of risperidone and aripiprazole in children with ASD. The only fair quality study
of risperidone in adults is consistent with the findings in children, but the strength of evidence
based upon the adult literature alone is insufficient to draw firm conclusions. Population studies
may be helpful to empirically group ASD patients by age in a way that fosters more effective
studies of treatments. Understanding the age-appropriateness of potential medical treatments as
based on social, physiological, pharmacological, and functional characteristics of the population
would help to prioritize future research, including the ways in which medical comorbidities arise
or increase as children with ASD move into adolescence and adulthood. Increased use of
standardized age groupings would facilitate comparisons of effectiveness within medical
intervention categories as well as with non-medical therapies. One way to support accomplishing
this is by developing treatment networks with adequate numbers of patients of varying ages to
participate in research.
Thus far, medication research in adolescents and young adults with ASD has been limited to
compounds that are already approved for other indications. As targeted treatments for ASD
emerge, initial studies will need to study adult populations to establish safety before moving into
studies of adolescents and finally children. Study of compounds not yet on the market could be
facilitated with partnerships between the academic and pharmaceutical communities. It will be
critical to consider the appropriate outcome measures and settings in which to study medication
response in adults. The heterogeneity in settings for adults with ASD is a significant impediment
to assessing symptom response. Ideally, medications would be combined with an educational or
psychosocial intervention that would mirror the school and therapeutic settings in which children
with ASD show improvements in social, communication, or behavioral function. Without some
level of educational or social challenge, it may be quite difficult to assess medication response.
Across all intervention types, research is needed on which outcomes to use in future studies.
The Aberrant Behavior Checklist is a widely used, easily repeatable, and highly sensitive
outcome measure for behavioral symptoms in ASD, but it does not directly index anxiety, mood,
social, or communication function, nor does it capture broader outcomes such as quality of life.
More outcome measures are needed to allow assessment of a broader range of symptoms,
particularly in individuals who may be higher functioning. No studies provide adequate
information on longer-term outcomes, and particularly on outcomes related to achieving goals
for independence and quality of life. To some degree, this reflects a lack of understanding and
consensus about optimal outcomes and how to measure them. We know little about which
outcome measures are most appropriate and valid for this population specifically; nor do we have
good, empirical evidence about which outcomes are valued by individuals and their families.
Furthermore, it is unclear which outcomes are most likely to change as a result of the very
different types of interventions assessed in this population. Substantial, foundational research
should be done to identify and validate outcome measures in the adolescent and young adult
population with ASD.
Research is also necessary to understand how individuals’ expression of ASD symptoms and
the severity of symptoms may affect treatment over the lifespan. Foundational research is
necessary to understand the goals of individuals with autism and their families as future research
studies are planned. Similarly, little research addressing the effects of family and caregiver
interactions and characteristics on the responses of individuals’ with ASD to interventions exists.
Finally, for all research in this area, we encourage greater transparency in reporting, particularly
as it relates to reporting of randomization approaches, characterization of study participants,
description of the intervention and measures of fidelity and adherence. These are all necessary to
understand correctly the potential impact of the interventions being reported.
Conclusions
Given the number of individuals affected by ASD, there is a dramatic lack of evidence on
best approaches to therapies for adolescents and young adults with these conditions. In
particular, families have little in the way of evidence-based approaches to support interventions
capable of optimizing the transition of teens with autism into adulthood. Most of the studies
identified were poor quality; while the five fair quality studies were primarily of medical
interventions. Behavioral, educational, and adaptive/life skills studies were typically small and
short term and suggested some improvements in social skills and functional behavior.
Individual studies also suggested that vocational programs may increase employment
success, but the studies were small. By the same token, few data address the effectiveness and
harms of medical or allied health interventions in the adolescent and young adult population.
Although the studies that have been conducted focused on the use of medications to address
specific challenging behaviors, the effectiveness in managing irritability and aggression in this
age group remains largely unknown and can at best be inferred from studies including mostly
younger children.
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74. García-Villamisar D, Wehman P, Navarro
MD. Changes in the quality of autistic
people's life that work in supported and
sheltered employment. A 5-year follow-up
study. J Vocat Rehabil. 2002;17(4):309-12.
75. García-Villamisar D, Ross D, Wehman P.
Clinical differential analysis of persons with
autism in a work setting: A follow-up study.
J Vocat Rehabil. 2000;14(3):183-5.
76. Laugeson EA, Frankel F, Gantman A, et al.
Evidence-based social skills training for
adolescents with autism spectrum disorders:
The UCLA PEERS Program. J Autism Dev
Disord. 2011 Aug 20. PMID: 21858588.
77. Verhoeven EW, Marijnissen N, Berger HJ,
et al. Brief report: Relationship between
self-awareness of real-world behavior and
treatment outcome in autism spectrum
disorders. J Autism Dev Disord. 2011 Jun
23PMID: 21698498.
78. Mandell DS, Morales KH, Marcus SC, et al.
Psychotropic medication use among
Medicaid-enrolled children with autism
spectrum disorders. Pediatrics. 2008
Mar;121(3):e441-8. PMID: 18310165.
79. Hollander E, Soorya L, Chaplin W, et al. A
double-blind placebo-controlled trial of
fluoxetine for repetitive behaviors and
global severity in adult autism spectrum
disorders. Am J Psychiatry. 2011;A iA:1-8.
80. Rendell JM, Gijsman HJ, Bauer MS, et al.
Risperidone alone or in combination for
acute mania. Cochrane Database Syst Rev.
2006(1):CD004043. PMID: 16437472.
81. Komossa K, Rummel-Kluge C, Schwarz S,
et al. Risperidone versus other atypical
antipsychotics for schizophrenia. Cochrane
Database Syst Rev. 2011(1):CD006626.
PMID: 21249678.
Acronyms and Abbreviations
ABC
Aberrant Behavior Checklist
ABC-C
Aberrant Behavior Checklist-Community Rating Scale
ABC-I
Aberrant Behavior Checklist-Community Rating Scale-Irritability
AHRQ
Agency for Healthcare Research and Quality
ASD
Autism spectrum disorders
BPVS
British Picture Vocabulary Scale
CARS
Childhood Autism Rating Scale
CGI-I
Clinical Global Impressions-Improvement
CGI-S
Clinical Global Impressions-Severity
DSM-III-R
Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised
DSM-IV
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
FC
Facilitated communication
G
Group
IQ
Intelligence quotient
KBIT2
Kaufman Brief Intelligence Test-Second Edition
KQ
Key Question
mg
Milligram
N, n
Number
NA
Not applicable
NR
Not reported
nRCT
Nonrandomized controlled trial
PDA
Personal digital assistant
PDD-NOS
Pervasive developmental disorder-not otherwise specified
PEP
PsychoEducational Profile
RCT
Randomized controlled trial
SD
Standard deviation
SIB-Q
Self-Injurious Behavior Questionnaire
SRI
Serotonin reuptake inhibitor
TEACCH
Treatment and Education of Autistic and Communication related Handicapped
Children
TEP
Technical Expert Panel
TOO
Task Order Officer
U.K.
United Kingdom
U.S.
United States
WAIS
Wechsler Adult Intelligence Scale
WASI
Wechsler Abbreviated Scale of Intelligence
Y-BOCS
Yale Brown Obsessive Compulsive Scale
Appendix A. Exact Search Strings and Results
Table A-1. PubMed search strategies (all searches last updated December 13, 2011)
Search Terms
Search
Results
#1
Autistic[tiab] OR autism[tiab] OR autistic disorder[mh] OR asperger syndrome[mh] OR child
development disorders, pervasive[mh:noexp] OR asperger[tiab] OR asperger's[tiab] OR aspergers[tiab]
OR pervasive development[tiab] OR pervasive developmental[tiab]
20485
#2
therapy[sh] OR therapeutics[mh] OR teaching[mh] OR psychotherapy[mh] OR treatment outcome[mh]
OR vocational education[mh] OR vocational guidance[mh] OR rehabilitation, vocational[mh] OR
vocational[tiab] OR transition[tiab] OR transitional[tiab] OR transitioning[tiab] OR transitions[tiab] OR
occupational[tiab] OR employment, supported[mh]
6387748
#3
#1 AND #2 AND eng[la] AND humans[mh]
5206
#4
#3 AND newspaper article[pt]
1
#5
#3 AND letter[pt]
301
#6
#3 AND comment[pt]
184
#7
#3 AND case reports[pt]
891
#8
#3 AND review[pt]
962
#9
#3 AND practice guideline[pt]
7
#10
#3 AND news[pt]
53
#11
#3 AND editorial[pt]
96
#12
#3 AND historical article[pt]
33
#13
#3 AND meta-analysis[pt]
33
#14
#3 AND legal cases[pt]
7
#15
#3 AND jsubsetk
29
#16
#3 NOT (#4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15)
2961
#17
#16 AND 1980:2012[dp]
2574
Key: [mh] = Medical Subject Heading; [tiab] = title/abstract word; [pt] = publication type; [sh] = subheading; [dp] =
publication date
*Note: numbers do not tally as some articles are excluded in more than one category.
Table A-2. PsycINFO search strategies (CSA interface)
Search Terms
Search
Results
#1
DE=("pervasive developmental disorders" or "aspergers syndrome" or "autism")
20109
#2
DE=("treatment" or "adjunctive treatment" or "aftercare" or "alternative medicine" or "acupuncture" or
"aromatherapy" or "faith healing" or "folk medicine" or "behavior modification" or "behavior therapy" or
"aversion therapy" or "covert sensitization" or "conversion therapy" or "dialectical behavior therapy" or
"exposure therapy" or "implosive therapy" or "systematic desensitization therapy" or "reciprocal inhibition
therapy" or "response cost" or "biofeedback training" or "classroom behavior modification" or
"contingency management" or "token economy programs" or "fading conditioning" or "omission training"
or "overcorrection" or "self management" or "self instructional training" or "time out" or "bibliotherapy"
or "cognitive techniques" or "cognitive restructuring" or "cognitive therapy" or "self instructional training"
or "computer assisted therapy" or "creative arts therapy" or "art therapy" or "dance therapy" or "music
therapy" or "poetry therapy" or "recreation therapy" or "crisis intervention services" or "hot line services"
or "suicide prevention centers" or "cross cultural treatment" or "cross cultural counseling" or "disease
management" or "health care services" or "continuum of care" or "long term care" or "mental health
services" or "community mental health services" or "palliative care" or "primary health care" or
"interdisciplinary treatment approach" or "involuntary treatment" or "medical treatment general" or "gene
therapy" or "milieu therapy" or "movement therapy" or "multimodal treatment approach" or "online
therapy" or "outpatient treatment" or "outpatient commitment" or "partial hospitalization" or "personal
therapy" or "physical treatment methods" or "acupuncture" or "artificial respiration" or "deep brain
stimulation" or "drug therapy" or "hormone therapy" or "narcoanalysis" or "sleep treatment" or
"polypharmacy" or "vitamin therapy" or "electrosleep treatment" or "gene therapy" or "phototherapy" or
"psychosurgery" or "thalamotomy" or "radiation therapy" or "shock therapy" or "electroconvulsive shock
therapy" or "insulin shock therapy" or "surgery" or "brain stimulation" or "brain self stimulation" or
"chemical brain stimulation" or "electrical brain stimulation" or "spreading depression" or "transcranial
magnetic stimulation" or "preventive medicine" or "psychotherapeutic techniques" or "animal assisted
therapy" or "autogenic training" or "cotherapy" or "dream analysis" or "guided imagery" or "mirroring" or
"morita therapy" or "motivational interviewing" or "mutual storytelling technique" or "paradoxical
techniques" or "psychodrama" or "psychotherapy" or "adlerian psychotherapy" or "adolescent
psychotherapy" or "analytical psychotherapy" or "autogenic training" or "behavior therapy" or "aversion
therapy" or "covert sensitization" or "conversion therapy" or "dialectical behavior therapy" or "exposure
therapy" or "implosive therapy" or "systematic desensitization therapy" or "reciprocal inhibition therapy"
or "response cost" or "brief psychotherapy" or "child psychotherapy" or "play therapy" or "client centered
therapy" or "cognitive behavior therapy" or "acceptance and commitment therapy" or "eclectic
psychotherapy" or "emotion focused therapy" or "existential therapy" or "experiential psychotherapy" or
"expressive psychotherapy" or "eye movement desensitization therapy" or "feminist therapy" or "geriatric
psychotherapy" or "gestalt therapy" or "group psychotherapy" or "encounter group therapy" or "marathon
group therapy" or "therapeutic community" or "guided imagery" or "humanistic psychotherapy" or
"hypnotherapy" or "age regression hypnotic" or "individual psychotherapy" or "insight therapy" or
"integrative psychotherapy" or "interpersonal psychotherapy" or "logotherapy" or "narrative therapy" or
"persuasion therapy" or "primal therapy" or "psychoanalysis" or "dream analysis" or "self analysis" or
"psychodrama" or "psychodynamic psychotherapy" or "psychotherapeutic counseling" or "family therapy"
or "conjoint therapy" or "rational emotive behavior therapy" or "reality therapy" or "relationship therapy"
or "solution focused therapy" or "supportive psychotherapy" or "transactional analysis" or "rehabilitation"
or "cognitive rehabilitation" or "neuropsychological rehabilitation" or "occupational therapy" or "physical
therapy" or "psychosocial rehabilitation" or "therapeutic social clubs" or "vocational rehabilitation" or
"supported employment" or "vocational evaluation" or "work adjustment training" or "relaxation therapy"
or "progressive relaxation therapy" or "social casework" or "social group work" or "sociotherapy" or
"speech therapy" or "treatment guidelines" or "self help techniques" or "self management" or "self
instructional training" or "therapeutic social clubs" or "medicinal herbs and plants" or "hypericum
perforatum" or "dietary supplements" or "diets" or "nutrition" or "vitamins" or "ascorbic acid" or "choline"
or "lecithin" or "folic acid" or "nicotinamide" or "nicotinic acid" or "vocational education" or
"occupational guidance" or "school to work transition" or "group homes" or "residential care institutions"
or "independent living programs" or "institutional schools" or "assisted living" or "therapeutic camps" or
556540
"mainstreaming" or "mainstreaming (educational)" or "special education")
#3
#1 and #2 and PT=(journal article) and (ME=(empirical study) or ME=(field study) or ME=(followup
study) or ME=(longitudinal study) or ME=(prospective study) or ME=(qualitative study) or
ME=(quantitative study) or ME=(retrospective study) or ME=(treatment outcome/clinical trial)), limited
to English language and human and peer-reviewed journals, citations from 1980 to present
1738
Key: DE = subject descriptor; PT = publication type; ME = methodology
Table A-3. ERIC search strategies (CSA interface)
Search Terms
Search
Results
#1
("pervasive developmental disorders") or autism or ("asperger syndrome")
8044
#2
DE=("therapy" or "educational therapy" or "group therapy" or "hearing therapy" or "music therapy" or
"occupational therapy" or "physical therapy" or "psychotherapy" or "milieu therapy" or "relaxation
training" or "speech therapy" or "therapeutic recreation" or "play therapy" or "art therapy" or
"bibliotherapy" or "drug therapy" or "intervention" or "crisis intervention" or "early intervention" or
"individualized family service plans" or "prereferral intervention" or "outcomes of treatment" or
"rehabilitation" or "special education" or "adapted physical education" or "therapeutic environment" or
"Dietetics" or "Food" or "Nutrition" or "vocational education" or "adult vocational education" or
"prevocational education" or "individualized transition plans" or "vocational rehabilitation" or "vocational
schools" or "vocational training centers" or "transitional programs" or "education work relationship" or
"supported employment" or "residential care" or "residential schools" or "residential programs" or
"residential institutions" or "boarding schools" or "resident camp programs" or "group homes")
138853
#3
#1 and #2, limited to peer reviewed journals, English only, and citations from 1980 to present
977
Key: DE = subject descriptor
Table A-4. CINAHL search strategies (EBSCO interface)
Search Terms
Search
Results
#1
(MH "Child Development Disorders, Pervasive") OR (MH "Asperger Syndrome") OR (MH "Autistic
Disorder"), limited to English language, human, research studies, and peer-reviewed journals, excluding
MEDLINE records
398
#2
#1 AND PT systematic review
16
#3
#1 AND PT review
1
#4
#1 AND PT case study
49
#5
#1 NOT (#2 OR #3 OR #4)
332
Key: MH = subject term
Note: CINAHL includes citations from 1981 to present so date limiting unnecessary for this search
Appendix B. Categorization of Study Designs
• Cohort, prospective: studies in which subjects receive more than one type of treatment or
exposure (e.g. ABA therapy or DIR/floortime compared with another treatment or no
treatment) in order to make comparisons of the outcomes of treatment, in which the
investigator(s) does not assign the treatment or non-treatment states for the purposes of
comparing them. For the purpose of this review, we termed studies with more than one
“exposure” group prospective cohorts to distinguish them from case series. Analysis is
focused on estimating the risk or odds of the outcome(s) based on the participants’ exposure
(treatment group status). These would include comparative studies in which the treatment is
set based on "happenstance" conditions such as availability of a therapist, or parental choice.
These types of studies can also be described as employing a nonrandomized pre-post group
comparison design.
• Cohort, retrospective: studies in which subjects having more than one type of treatment
(more than one “exposure”) are identified after having had intervention (e.g., chart review of
children with ASD receiving either risperidone or olanzapine). Studies that have some
component of follow-up should be classified as retrospective if the intent to follow-up the
cohort was not designed and future data collection planned prior to the time of the treatment
under investigation. Analysis estimates the risk or odds of the outcome(s) based on the
participants’ exposure (treatment group status).
• Randomized clinical trials: special instances of prospective cohorts in which the “exposure”
or treatment group is assigned by the investigator through use of an allocation method;
treatment and nontreatment are assigned by study investigators using an a priori protocol.
• Controlled trials (nonrandomized): special instances of prospective cohorts in which the
exposure or treatment group is assigned by the investigator but without using a
randomization scheme.
• Case-control studies: studies that identify cases based on the outcome under study. A control,
comparison population is identified that is intended to be a representative sample of similar
children. In order to assure similar characteristics overall with respect to covariates not being
studied, matching is often used, such as matching on age or race to assure a similar
distribution of these potential confounders. Analysis is technically estimating the odds of
having had a particular exposure or characteristic given known presence or absence of the
outcome.
• Case series, prospective: studies in which subjects (ideally consecutive participants) having
the same type of treatment for symptoms of ASD are identified prior to treatment and
consented to participate (i.e., all participants receive the same treatment). The components of
the study and outcome follow-up are designed before the participants are enrolled. Data
analysis is descriptive including the full range of potential outcome measures such as
reduction in problem behaviors, changes in IQ, etc. Analysis may include construction of
predictive models that seek to examine influences on outcomes, such as IQ at intake, etc.
Studies may also present data for groups of participants (e.g., males vs. females) though all
participants received the same treatment. Case series might include experimental approaches
or analyses such as multiple baseline, reversal, ABAB, alternating treatments, or changing
criterion studies in this literature. Group designed studies from which we could only collect
data from one arm (e.g., studies that inappropriately compared the effects of an intervention
in children with ASD with normally developing children) were considered case series.
• Case series, retrospective: studies in which investigators obtain permission to review existing
clinical records in order to summarize the outcomes from a sequence (ideally consecutive
patients) receiving the same treatment. Followup of the members of a case series identified
from medical records or databases using methods such as surveys should still be counted as
“retrospective” if the design of the study and future data collection were not established prior
to the time of the treatment under study. Analysis is descriptive.
Appendix C. Sample Data Extraction Forms
Interventions for Adolescents and Young Adults with Autism Comparative Effectiveness Review --
Abstract Review Form
First Author, Year: __________________ Reference ID #: __________ Abstractor Initials: ___ ___ ___
Primary Inclusion/Exclusion Criteria
1. Includes:
__ participants diagnosed with ASD (Autism, Aspergers, PDD-NOS)
between the ages of 13-30
__caregivers/family members of individuals ages 13-30 with ASDs
Yes
(if at least 1
marked,
circle Yes)
No
Cannot
Determine
2. Original research (exclude editorials, commentaries, letters, reviews,
etc.)
Yes
No
Cannot
Determine
3. Eligible study size ( = 20 individuals with ASDs between ages 13-30)
N ages 13-30=____
Yes
No
Cannot
Determine
4. Addresses any of the following in individuals with ASD between the
ages of 13-30:
a. __treatment modality intended to modify core symptoms of
ASD
b. __treatment modality intended to modify medical or mental
health comorbidities (e.g., epilepsy, sleep disorders, depression,
anxiety, acute and episodic aggression, motor skills, etc.)
c. __treatment modality intended to affect functional behavior,
attainment of goals toward independence, educational attainment,
occupational attainment, life satisfaction, residential outcomes,
social outcomes, and relationship-focused outcomes
d. __treatment modality intended to assist with transitional issues
(e.g., attainment of goals toward independence, educational
attainment, occupational attainment, life satisfaction, access to
services, legal outcomes, and social outcomes)
e. __treatment modality intended to affect family adaptation or
family outcomes
f. __ harms/adverse effects associated with treatment
Yes
(if at least 1
element
marked,
circle Yes)
No
Cannot
Determine
Retain for: _____BACKGROUND/DISCUSSION _____REVIEW OF REFERENCES
_____Other________________________________________
COMMENTS:
Interventions for Adolescents and Young Adults with Autism Comparative Effectiveness Review --
Full Text Review Form
First Author, Year: __________________ Reference ID #: __________ Abstractor Initials: ___ ___ ___
1. Includes one of the following:
1a. Only individuals between the ages 13 and 30 with ASD
Yes
No
1b. Mean age of participants with ASD is within range of 13-30
Yes
No
1c. At least 50% of participants with ASD in age range 13-30
Yes
No
1d. Family members of individuals in the target population
Yes
No
2. Original research (exclude editorials, commentaries, letters, reviews, systematic
reviews, meta analyses, etc.)
Yes
No
3. Eligible study size N = 20 TOTAL in target age range
Yes
No
4. Study addresses one or more of the following questions (check applicable KQ
below):
Yes
No
__KQ1: Among adolescents and young adults with autism spectrum disorders (ASDs), what are
the effects of available interventions* on the core symptoms of ASD?
__KQ2: Among adolescents and young adults with ASD, what are the effects of available
interventions (see KQ1*) on common medical and mental health comorbidities (e.g., epilepsy,
sleep disorders, obesity, motor impairments, depression, anxiety, acute and episodic aggression,
ADHD etc.)?
__KQ3: Among adolescents and young adults with ASD, what are the effects of available
interventions (see KQ1*) on functional behavior, attainment of goals toward independence,
educational attainment, occupational/vocational attainment, life satisfaction, access to health and
other services, legal outcomes, and social outcomes?
__KQ4: Among adolescents and young adults with ASD, what is the effectiveness of
interventions designed to support the transitioning process, specifically to affect attainment of
goals toward independence, educational attainment, occupational/vocational attainment, life
satisfaction, access to health and other services, legal outcomes, and social outcomes?
__KQ5: Among adolescents and young adults with ASD, what harms are associated with
available interventions (see KQ1*)?
__KQ6: What are the effects of interventions on family outcomes?
Treatment area studied (circle applicable: behavioral, educational, medical, allied health,
CAM, transitional support, family-focused, vocational, crisis management, sex education,
exercise/recreational, residential supports, other:________________________ )
5. Study published in English
Yes
No
EXCLUDE IF AN ITEM IN A GRAY BOX IS SELECTED
6. If excluded, retain for ____Background/Discussion ___Review of references ___Other:
_____________________
Comments:
* Available interventions may include the following broad categories: social skills,
psychopharmacology, functional behavioral interventions, psychoeducational interventions,
vocational and independent living skills training, targeted educational interventions, transition
support, complementary and alternative medicine (CAM), diet/nutrition therapies, crisis
management, sexual education, case management, family-focused interventions,
exercise/recreational interventions, applied behavior analysis, allied health (e.g.,
speech/language, physical, and occupational therapies), and residential supports.
Appendix D. Evidence Tables
Tables are sorted by year, then last name of first author.
Table D-1. Interventions for adolescents and young adults with autism evidence table
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Garcia-Villamisar
et al., 2010
Country:
Spain
Enrollment
period:
NR
Funding:
NR
Author industry
relationship
disclosures:
NR
Design:
RCT
Intervention:
Leisure/recreation
program including
interaction with media,
exercise, game playing,
and other recreational
activities for 2 hrs/day
Intervention target:
Quality of life and stress
Primary outcome:
NR
Groups:
G1: leisure program
G2: wait list control
Treatment duration:
12 months
Frequency of contact
during study:
Baseline and after 12
months
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1: 37
G2: 34
N at followup:
G1: 37
G2: 34
Inclusion criteria:
• Attendance at day
program for adults with
special needs
• Consent to participate in
study
Exclusion criteria:
• See inclusion criteria
Age, yrs, mean ± SD,
(range):
G1: 31.49 ± 4.83 (17-39)
G2: 30.06 ± 3.44 (24-38)
Mental age (Leiter),
months, mean ± SD:
G1: 63.46 ± 21.33
G2: 61.44 ± 9.37
Gender, n:
Male:
G1: 22
G2: 19
Female:
G1: 15
G2: 15
DSM-based diagnostic
approach reported:
No
Leiter test, mean ±
SD:
G1: 63.46 ± 21.33
G2: 61.44 ± 9.37
Stress Survey
Schedule, mean ±
SD:
G1: 114.03 ± 19.90
G2: 116.94 ± 18.61
Quality of Life
Questionnaire,
mean ± SD:
Total score:
G1: 50.59 ± 2.93
G2: 54.17 ± 2.90
Empower/
independence:
G1: 12.13 ± 1.18
G2: 13.06 ± 1.81
Satisfaction:
G1: 15.29 ± 2.32
G2: 16.23 ± 1.21
Competence/
productivity:
G1: 7.62 ± 1.08
G2: 7.64 ± .73
Social/integration:
G1: 15.54 ± 2.06
G2: 17.23 ± 2.04
Leiter test, mean
± SD:
G1: 62.16 ± 18.84
G2: 61.79 ± 14.87
Stress Survey
Schedule, mean
± SD:*
G1: 103.19 ±
19.27
G2: 117.67 ±
16.25
G1/G2: P < 0.001
Quality of Life
Questionnaire,
mean ± SD:*
Total score:
G1: 63.62 ± 8.99
G2: 55.29 ± 3.45
G1/G2: P < 0.001
Empower/
independence:
G1: 13.24 ± 1.88
G2: 14.26 ± 1.60
G1/G2: P = NS
Satisfaction:
G1: 22.03 ± 2.92
G2: 15.03 ± 0.93
G1/G2: P < 0.001
Competence/
productivity:
G1: 11.35 ± 4.08
G2: 7.82 ± 7.33
G1/G2: P < 0.001
Social/integration:
G1: 17.00 ± 2.40
G2: 18.17 ± 2.11
G1/G2: P = NS
Harms:
NR
Interventions for adolescents and young adults with autism evidence table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Gentry et al., 2010
Country:
US
Enrollment
period:
NR
Funding:
Commonwealth
Neurotrauma
Initiative
Author industry
relationship
disclosures:
NR
Design:
Prospective case
series
Intervention:
Four home-based training
visits on the use of a
personal digital assistant
as a cognitive aid.
Intervention target:
Executive function-
related tasks (memory,
organization, planning,
and goal-direction).
Primary outcome:
Occupational
performance and
satisfaction (COPM);
satisfaction, usage, and
retention (FATCAT).
Groups:
G1: PDA training
Treatment duration:
10-14 days
Frequency of contact
during study:
As needed via phone or
email (only initiated by
participants)
Last followup post-
treatment:
8 weeks
Measure of treatment
fidelity/adherence
reported:
Yes
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1: 22
N at followup:
G1: 22
Inclusion criteria:
• Autism diagnosis and
current IEP
• At least 14 years old
• Attending public school
in Virginia
• Demonstrate sufficient
dexterity
• Functional vision and
hearing
• Caregiver willing to
participate in
assessment
• Home personal
computer
Exclusion criteria:
• See inclusion criteria
Age, yrs, mean (range):
G1: 16.5 (14-18)
Mental age:
NR
Gender, n (%):
Male:
G1: 18 (82)
Female:
G1: 4 (18)
DSM-based diagnostic
approach reported:
No
COPM score,
mean:
Performance:
G1: 2.82
Satisfaction:
G1: 2.05
COPM score,
mean:
Performance:
G1: 6.64
G1/BL: P < 0.001
Satisfaction:
G1: 6.32
G1/BL: P < 0.001
FATCAT, n (%):
Used PDA daily:
G1: 22 (100)
Want to continue
using:
G1: 22 (100)
Can program
without help:
G1: 16 (73)
Device is a waste
of time:
G1: 0 (0)
Harms:
NR
Interventions for adolescents and young adults with autism evidence table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Greher et al., 2010
Country:
US
Enrollment
period:
NR
Funding:
NR
Author industry
relationship
disclosures:
NR
Design:
Prospective case
series
Intervention:
SoundScape music
intervention, 90 minutes
per week
Intervention target:
NR
Primary outcome:
NR
Groups:
G1: music intervention
G2: parental evaluations
Treatment duration:
8 weeks
Frequency of contact
during study:
Weekly
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1: 22
N at followup:
G1: 22
Inclusion criteria:
• Autism spectrum
diagnosis
• Aged between 13-30
• No severe behavioral
challenges
Exclusion criteria:
• See inclusion criteria
Age, yrs, mean (range):
G1: 18 (13-29)
Mental age:
NR
Gender:
NR
DSM-based diagnostic
approach reported:
No
NR
Feedback
questionnaire
ratings (scale 1-
10), mean:
How enjoyable
have you [your
child] found the
music program?
G1: 7.86
G2: 7.91
How interesting
have you [your
child] found the
music program?
G1: 7.82
G2: 7.95
How much do you
believe you [your
child] have
benefited socially
from the music
program?
G1: 6.95
G2: 6.86
Feedback
questionnaire, n:
Have you [your
child] made any
friends in the
music program?
Yes:
G1: 19
G2: 11
Kind of/not sure:
G1: 1
G2: 4
No:
G1: 2
G2: 6
Harms:
NR
Interventions for adolescents and young adults with autism evidence table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Valenti et al., 2010
Country:
Italy
Enrollment
period:
April 2007 to
March 2009
Funding:
Italian National
Health System
Author industry
relationship
disclosures:
None
Design:
Prospective case
series
Intervention:
Intensive behavioral
treatment at a semi-
residential rehabilitation
center for autism.
Intervention target:
Adaptive functioning
Primary outcome:
Adaptive functioning
(VABS)
Groups:
G1: intensive behavioral
treatment
G1a: female adolescents
G1b: male adolescents
Treatment duration:
2 years
Frequency of contact
during study:
Yearly
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
Yes
Co-interventions held
stable during treatment:
NR
Concomitant therapies,
n (%):
Psychoactive drugs:
G1: 12 (35.3)
N at enrollment:*
G1: 34
N at followup:*
G1: 34
Inclusion criteria:
• Diagnosis of ASD
• Regular public school
attendance
• Consent of parent or
tutor
Exclusion criteria:
• See inclusion criteria
Age, range:
G1: post-pubescent
adolescents up to 18 yrs
Mental age:
NR
Gender, n (%):
Male:
G1: 23 (68)
Female:
G1: 11 (32)
DSM-based diagnostic
approach reported:
Yes
VABS score, mean
± SD:
Communication:
G1a: 72.59 ± 9.78
G1b: 84.18 ± 7.20
Daily living
G1a: 80.77 ± 8.64
G1b: 80.66 ± 8.66
Socialization:
G1a: 68.18 ± 8.82
G1b: 75.84 ± 6.53
Motor skills:
G1a: 74.88 ± 8.39
G1b: 94.93 ± 9.57
VABS score,
year 1, mean ±
SD:
Communication:
G1a: 70.40 ± 7.97
G1b: 84.31 ± 7.75
Daily living:
G1a: 78.21 ± 9.27
G1b: 86.57 ± 8.26
Socialization:
G1a: 73.04 ± 8.99
G1b: 77.60 ± 8.20
Motor skills:
G1a: 84.07 ± 7.80
G1b: 99.41 ± 8.80
VABS score,
year 2, mean ±
SD:
Communication:
G1a: 73.23 ± 8.64
G1b: 87.93 ± 7.44
G1a/BL: ES =
0.02
G1b/BL: ES =
0.11
Daily Living:
G1a: 87.08 ± 8.38
G1b: 88.67 ± 8.87
G1a/BL: ES =
0.22
G1b/BL: ES =
0.19
Socialization:
G1a: 75.60 ± 8.02
G1b: 83.20 ± 8.92
G1a/BL: ES =
0.26
G1b/BL: ES =
0.23
Motor Skills:
G1a: 85.16 ± 6.37
G1b: 102.42 ±
8.39
G1a/BL: ES =
0.20
G1b/BL: ES =
0.16
Harms:
NR
Interventions for adolescents and young adults with autism evidence table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Laugeson et al.,
2009
Country:
US
Enrollment
period:
NR
Funding:
NIH, NIMH
Author industry
relationship
disclosures:
NR
Design:
RCT
Intervention:
Program for the Education
and Enrichment of
Relational Skills (PEERS)
outpatient social skills
program; weekly 90
minute sessions
Groups:
G1: PEERS
G2: delayed treatment
control
Intervention target:
Improve friendship quality
and social skills in teens
Primary outcome:
NR
Treatment duration:
12 weeks
Frequency of contact
during study:
Weekly visits
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
Yes
Co-interventions held
stable during treatment:
Yes
Concomitant therapies,
n:
Lithium carbonate,
quetiapine
G1: 1
G2: 0
Dexamethylphenidate,
buproprion:
G1: 1
G2: 0
Methylphenidate:
G1: 1
G2: 0
Fluoxetine:
G1: 0
G2: 1
Atomoxetine, aripiprazole,
oxycarbazepine:
G1: 0
G2: 1
Inclusion criteria:
• Chronological age 13-17
years
• Social problems as
reported by the parent
• Previous diagnosis of
either high functioning
• Autism, Asperger’s
Disorder, or PDD-NOS
• English fluency of the
teen
• Parent or family member
who was a fluent English
speaker and who was
willing to participate in
the study
• Verbal IQ = 70 on the K-
BIT-2
• No history of major
mental illness (e.g.,
bipolar disorder,
schizophrenia,
psychosis)
• Absence of hearing,
visual, or physical
impairments which
precluded teen from
participating in outdoor
sports activities
• Teens who verbally
expressed an interest in
participating in the
intervention during the
eligibility appointment
Exclusion criteria:
• See inclusion criteria
Age, yrs, mean ± SD:
G1: 14.6 ± 1.3
G2: 14.6 ±1.6
IQ, mean ± SD:
G1: 96 ± 16.1
G2: 88.3 ± 21.1
Gender, %:
Male:
G1: 88.2
G2: 81.2
Female:
G1: 11.8
G2: 18.8
VABS score, mean
± SD:
Communication:
G1: 72.2 ± 6.2
G2: 70.6 ± 6.6
Socialization:
G1: 65.8 ± 8.5
G2: 65.9 ± 7.0
Composite:
G1: 70.3 ± 8.5
G2: 68.6 ± 6.2
TASSK score, teen
report, mean ± SD:
G1: 13.3 ± 2.4
G2: 12.6 ± 3.6
QPQ score, teen
report, mean ± SD:
Host:
G1: 1.1 ± 1.4
G2: 0.6 ± 0.9
Guest:
G1: 0.9 ± 1.3
G2: 1.3 ± 2.3
Conflict:
G1: 4.1 ± 5.2
G2: 4.3 ± 4.5
FQS score, teen
report, mean ± SD:
G1: 16.8 ± 3.4
G2: 18.1 ± 3.9
QPQ score, parent
report, mean ± SD:
Host:
G1: 1.5 ± 2.7
G2: 0.6 ± 0.9
Guest:
G1: 0.9 ± 1.3
G2: 1.3 ± 2.5
Conflict:
G1: 6.5 ± 5.0
G2: 6.9 ± 5.6
SSRS score,
parent report,
mean ± SD:
Social skills:
G1: 80.2 ± 8.8
G2: 77.9 ± 12.1
Problem behaviors:
G1: 114.9 ± 14.2
G2: 120.7 ± 13.6
TASSK score,
teen report,
mean ± SD:
G1: 19.6 ± 1.4
G2: 13.3 ± 3.8
G1/G2: P <
0.0001
G1/BL: P < 0.01
G2/BL: P = NS
QPQ score, teen
report, mean ±
SD:
Host:
G1: 3.2 ± 2.2
G2: 1.1 ± 1.3
G1/G2: P < 0.025
G1/BL: P < 0.01
G2/BL: P = NS
FQS score, teen
report, mean ±
SD:
G1: 17.2 ± 4.0
G2: 16.6 ± 4.6
G1/G2: P < 0.05
G1/BL: P = NS
G2/BL: P < 0.05
SSRS score,
parent report,
mean ± SD:
Social skills:
G1: 89.7 ± 12.1
G2: 79.8 ± 11.7
G1/G2: P < 0.05
G1/BL: P < 0.01
G2/BL: P = NS
Harms:
NR
Interventions for adolescents and young adults with autism evidence table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Laugeson et al.,
2009 (continued)
Paroxetine:
G1: 0
G2: 1
N at enrollment:
Total: 35*
N at followup:
G1: 17
G2: 16
DSM-based diagnostic
approach reported:
NR (diagnosis by
community/university/
school psychologists)
SSRS score,
teacher report,
mean ± SD:
Social skills:
G1: 83.6 ± 7.3 (n=8)
G2: 86.6 ± 14.8
(n=5)
Problem behavior:
G1: 96.5 ± 16.7
(n=8)
G2: 85.4 ± 21.3
(n=5)
Interventions for adolescents and young adults with autism evidence table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Lawer et al., 2009
Country:
US
Enrollment
period:
NR
Funding:
NR
Author industry
relationship
disclosures:
NR
Design:
Cross-sectional
study
Intervention:
NA
Intervention target:
NR
Primary outcome:
NR
Groups:
G1: Individuals with ASD
in US Vocational
Rehabilitation System
Treatment duration:
NA
Frequency of contact
during study:
NA
Last followup post-
treatment:
NA
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1: 1,707
N at followup:
G1: 1,707
Inclusion criteria:
• Age 18-65
• Individuals receiving
vocational rehabilitation
services from the US
Rehabilitation Services
Administration whose
cases were closed in
2005 for reasons other
than death or lack of
need for services
Exclusion criteria:
• See inclusion criteria
Age, yrs, n (%):
18-25:
G1: 1,253 (73.4)
25-34:
G1: 265 (15.5)
35-44:
G1: 138 (8.1)
45-54:
G1: 43 (2.5)
55-65:
G1: 8 (0.5)
Mental age:
NR
Gender, n (%):
Male:
G1: 1,434 (84)
DSM-based diagnostic
approach reported:
No
NR
Case deemed too
severe to benefit from
services, n (%):
G1: 74 (4.3)
Vocational outcomes
at closure, n (%):
Not employed: G1: 909
(55.7)
Employed in sheltered
setting:
G1: 35 (2.1)
Competitive
employment:
G1: 689 (42.2)
Received on-the-job
supports at any time,
by vocational outcome,
n (%):
Not employed:
G1: 115 (12.7)
Employed in sheltered
setting:
G1: 23 (65.7)
Competitive
employment:
G1: 391 (56.8)
Education at closure, n
(%):
< high school:
G1: 739 (43.7)
High school or GED:
G1: 642 (38.0)
> high school:
G1: 309 (18.3)
Cost of services
among those with any
expenditures, median:
G1: $2,380 (n=1,229)
Average expenditure
for purchased
services, mean ± SD:
G1: $3,324 ± $5,662
Harms:
NR
Interventions for adolescents and young adults with autism evidence table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Jewell et al., 2007
Country:
US
Enrollment
period:
NA
Funding:
NR
Author industry
relationship
disclosures:
NR
Design:
Retrospective
case series
Intervention:
Rotating classroom
schedule in a not-for-profit
school for children with
autism.
Intervention target:
NR
Primary outcome:
Number of crisis inter-
ventions and the time
spent in crisis intervention
Groups:
G1: Adolescent students
with rotating classroom
schedule
Treatment duration:
NR
Frequency of contact
during study:
Daily
Last followup post-
treatment:
NA
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1: 55
N at followup:
G1: 55
Inclusion criteria:
• Enrolled at the study
school
• Primary diagnosis of
autism
• Diagnosed by a
psychologist from the
student’s home school
Exclusion criteria:
• Other primary diagnosis
(e.g. behavior disorder
or Rhett’s)
Age, yrs, mean (range):
G1: 17.63 (14-22)
Mental age:
NR
Gender, n (%):
Male:
G1: 44 (80)
Female:
G1: 11 (20)
DSM-based diagnostic
approach reported:
No
Number of crisis
events, mean ± SD:
G1: 2.44 ± 6.39
Time in crisis, min,
mean ± SD:
G1: 40.27 ± 102.08
Number of crisis
events, mean ±
SD:
G1: 2.22 ± 5.88
G1/BL: P = 0.84
Time in crisis,
min, mean ± SD:
G1: 28.96 ± 65.47
G1/BL: P = 0.83
Harms:
NR
Interventions for adolescents and young adults with autism evidence table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline Measures
Outcomes
Author:
Tse et al., 2007
Country:
Canada
Enrollment
period:
NR
Funding:
NR
Author industry
relationship
disclosures:
NR
Design:
Prospective case
series
Intervention:
Social skills training for
adolescents with
Asperger’s syndrome and
high-functioning autism in
psychiatry clinic.
Psycho-educational and
experiential methods of
teaching social skills, with
emphasis on learning
through role play. Each
group enrolled 7-8
adolescents.
Intervention target:
Social competence and
problem behaviors
Primary outcome:
NR
Groups:
G1: Social skills group
Treatment duration:
12 weeks
Frequency of contact
during study:
Weekly
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies,
n (%):
Psychotropic medication:
17 (37)
Atypical antipsychotics: 6
(NR)
Selective serotonin
reuptake inhibitors: 5 (NR)
Methylphenidate: 5 (NR)
N at enrollment:
G1: 46
N at followup:
G1: 32
Inclusion criteria:
• Diagnosis of an autism
spectrum disorder by a
child psychiatrist
• Adequate language skills
for participation in
activities; being able to
talk about their interests
and to verbalize some
goals for participation
and willingness to attend
Exclusion criteria:
• See inclusion criteria
Age, yrs, mean ± SD
(range):
G1: 14.6 ±1.7 (13-18)
Mental age:
NR
Gender, %:
Male:
G1: 61
Female:
G1: 39
DSM-based diagnostic
approach reported:
NR
SRS score, mean ±
SD (n = 32): Total:
G1: 95.9 ± 27.9
Social awareness:
G1: 12.0 ± 4.0
Social cognition:
G1: 16.9 ± 5.8
Social
communication:
G1: 32.9 ± 9.8
Social motivation:
G1: 15.8 ± 5.7
Autistic
mannerisms:
G1: 18.2 ± 7.3
DSM social aspects:
G1: 69.1 ± 19.4
DSM language
aspects:
G1: 8.5 ± 3.4
DSM
preoccupations/
mannerisms:
G1: 18.2 ± 7.3
N-CBRF Positive
Social score, mean
± SD (n = 30):
Total:
G1: 13.9 ± 4.4
Compliant/calm:
G1: 8.6 ± 3.1
Adaptive social:
G1: 5.3 ± 2.0
ABC score, mean ±
SD (n = 30):
Total:
G1: 41.9 ± 22.1
Irritability:
G1: 8.9 ± 6.8
Lethargy/
withdrawal:
G1: 12.8 ± 7.5
Stereotypic
behavior:
G1: 4.7 ± 3.8
SRS score, mean
± SD (n = 32):
Total:
G1: 84.9 ± 28.3
G1/BL: P = 0.003,
ES = 0.39
Social awareness:
G1: 11.5 ± 4.1
G1/BL: P = 0.321,
ES = 0.12
Social cognition:
G1: 15.0 ± 5.4
G1/BL: P = 0.009,
ES = 0.34
Social
communication:
G1: 28.3 ± 10.1
G1/BL: P = 0.002,
ES = 0.46
Social motivation:
G1: 13.6 ± 5.8
G1/BL: P = 0.013,
ES = 0.38
Autistic
mannerisms:
G1: 16.5 ± 6.8
G1/BL: P = 0.058,
ES = 0.24
DSM social
aspects:
G1: 60.7 ± 19.8
G1/BL: P = 0.001,
ES = 0.43
DSM language
aspects:
G1: 7.7 ± 3.5
G1/BL: P = 0.107,
ES = 0.23
DSM
preoccupations/
mannerisms:
G1: 16.5 ± 6.8
G1/BL: P = 0.058,
ES = 0.24
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline Measures
Outcomes
Tse et al., 2007
(continued)
Hyperactivity:
G1: 12.1 ± 8.9
Inappropriate
speech:
G1: 3.5 ± 2.6
N-CBRF Problem
Behavior score,
mean ± SD (n =
30):
Total:
G1: 51.3 ± 24.7
Conduct problems:
G1: 10.2 ± 7.8
Insecure/anxious:
G1: 13.0 ± 6.2
Hyperactive:
G1: 8.3 ± 5.4
Self-injure/
stereotypic:
G1: 1.3 ± 1.8
Self-isolated/
ritualistic:
G1: 7.9 ± 5.2
N-CBRF Positive
Social score,
mean ± SD (n =
30):
Total:
G1: 16.0 ± 5.5
G1/BL: P = 0.024,
ES = 0.42
Compliant/calm:
G1: 10.0 ± 3.8
G1/BL: P = 0.052,
ES = 0.40
Adaptive social:
G1: 6.0 ± 2.3
G1/BL: P = 0.060,
ES = 0.32
ABC score,
mean ± SD (n =
30):
Total,
G1: 27.9 ± 16.5
G1/BL: P = 0.001,
ES = 0.72
Irritability:
G1: 4.9 ± 4.0
G1/BL: P = 0.002,
ES = 0.72
Lethargy/
withdrawal:
G1: 9.0 ± 7.5
G1/BL: P = 0.008,
ES = 0.51
Stereotypic
behavior:
G1: 2.8 ± 2.9
G1/BL: P = 0.005,
ES = 0.56
Hyperactivity: G1:
9.0 ± 7.4
G1/BL: P = 0.029,
ES = 0.38
Inappropriate
speech:
G1: 2.2 ± 1.8
G1/BL: P = 0.003,
ES = 0.58
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline Measures
Outcomes
Tse et al., 2007
(continued)
N-CBRF Problem
Behavior score,
mean ± SD (n =
30):
Total:
G1: 38.6 ± 19.7
G1/BL: P = 0.005,
ES = 0.57
Conduct
problems:
G1: 7.7 ± 6.7
G1/BL: P = 0.046,
ES = 0.34
Insecure/ anxious:
G1: 10.5 ± 5.6:
G1/BL: P = 0.040,
ES = 0.42
Hyperactive:
G1: 7.0 ± 4.9
G1/BL: P = 0.257,
ES = 0.25
Self-injure/
stereotypic:
G1: 0.7 ± 1.1
G1/BL: P = 0.022,
ES = 0.40
Self-isolated/
ritualistic:
G1: 5.5 ± 3.7
G1/BL: P = 0.003,
ES = 0.53
Feedback
surveys, teen
report, n:
Liking the group:
10/13
Liked it a lot: 5/13
Disliking the
group: 1/13
Improvement in
‘‘having a
conversation”:
A lot: 7/13
Some: 5/13
Made friends in
the group: 12/13
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline Measures
Outcomes
Tse et al., 2007
(continued)
Feedback
surveys, parent
report, n:
Child seemed
happy to attend
the group: 15/17
Overall
improvement in
their child’s social
behavior:
A little: 10
The same: 3
Much better or
very much better:
3
Harms: NR
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Garcia-Villamisar
et al., 2006
Country:
Spain
Enrollment
period:
NR
Funding:
Fondo Social
Europeo,
Cosejería de
Asuntos Sociales
de la Comunidad
Autónoma de
Madrid (Spain)
Author industry
relationship
disclosures:
NR
Design:
Prospective
cohort
Intervention:
Sheltered and supported
community-based work
environments
Intervention target:
Cognitive performance
Groups:
G1: Supported
employment
G2: Unemployed
Primary outcome:
NR
Treatment duration:
Average length of
community employment:
30 months for an average
of 20 hours/week
Frequency of contact
during study:
Beginning and end of
program
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
Yes
Co-interventions held
stable during treatment:
NR with exception of
medication free at testing
Concomitant therapies:
NR
N at enrollment:
G1+G2: 44
N at followup:
G1+G2: 44
Inclusion criteria:
• Diagnosis of autism
• For G2, sheltered
workshops enrollment
prior to participation in
supported work program
• No severe behavior
problems
• Acceptable professional
and vocational abilities
• Medication free at the
time of testing
• Score above 35th
percentile point on the
Standard Progressive
Matrices (SPM)
Exclusion criteria:
• History of psychiatric
disorder, neurological
disorder or head injury
Age, yrs, mean ± SD:
G1: 25.52 ± 3.35
G2: 24.32 ± 4.34
IQ, Leiter (total score),
mean ± SD: NR
Gender, n:
Male:
G1+G2: 32
Female:
G1+G2: 12
DSM-based diagnostic
approach reported:
Yes (DSM-IV & CARS)
Big Circle/Little
Circle score, mean
± SD:
G1: 39.38 ± 0.97
G2: 39.52 ± 0.73
G1/G2: P = NS
Spatial Span Task
score, mean ± SD:
G1: 3.90 ± 0.14
G2: 3.78 ± 1.17
G3: P = NS
Spatial Working
Memory Task
score, mean ± SD:
Between errors:
G1: 68.14 ± 14.55
G2: 67.91 ± 13.2
G1/G2: P = NS
Strategy:
G1: 38.19 ± 2.11
G2: 39.26 ± 2.84
G1/G2: P = NS
Intradimensional/
Extradimensional
score, mean ± SD:
Stages completed:
G1: 7.48 ± 5.11
G2: 7.39 ± 0.94
G1/G2: P = NS
Errors:
G1: 16.90 ± 10.94
G2: 19.69 ± 10.75
G1/G2: P = NS
Planning task
‘Stockings of
Cambridge’ score,
mean ± SD:
Problems solved in
minimum moves:
G1: 5.10 ± 2.47
G2: 5.91 ± 2.45
G1/G2: P = NS
Average planning
time:
G1: 6.71 ± 3.02
G2: 6.91 ± 3.38
G1/G2: P = NS
Big Circle/Little
Circle score,
mean ± SD:
G1: 39.48 ± 0.87
G2: 39.25 ± 0.96
G1/G2: P = NS
Spatial Span
Task score,
mean ± SD:
G1: 4.85 ± 0.79
G2: 3.96 ± 0.93
G1/G2: P < 0.05
Spatial Working
Memory Task
score, mean ±
SD:
Between errors:
G1: 61.91 ± 12.38
G2: 66.13 ± 13.19
G1/G2: P < 0.001
Strategy:
G1: 34.00 ± 2.19
G2: 37.43 ± 2.92
G1/G2: P < 0.001
Intradimen-
sional/ Extra-
dimensional
score, mean ±
SD:
Stages
completed:
G1: 7.43 ± 0.51
G2: 7.30 ± 0.47
G1/G2: P = 0.02
Errors:
G1: 12.71 ± 6.71
G2: 17.13 ± 9.15
G1/G2: P = NS
Planning task
‘Stockings of
Cambridge’
score, mean ±
SD:
Problems solved
in minimum
moves:
G1: 7.38 ± 1.80
G2: 5.57 ± 1.88
G1/G2: P < 0.01
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Garcia-Villamisar
et al., 2006
(continued)
Trail Making Test –
part B score, mean
± SD:
G1: 55.48 ± 18.27
G2: 66.22 ± 23.75
G1/G2: P = NS
Matching Familiar
Figures Test score,
mean ± SD:
Time of 1st answer:
G1: 16.33 ± 4.86
G2: 17.43 ± 3.91
G1/G2: P = NS
Errors:
G1: 7.76 ± 2.84
G2: 7.96 ± 3.62
G1/G2: P = NS
Word fluency test
score, mean ± SD:
G1: 39.38 ± 0.97
G2: 39.52 ± 0.73
G1/G2: P = NS
CARS score, mean
± SD:†
G1: 34.81 ± 5.19
G2: 33.19 ± 6.65
Average planning
time:
G1: 4.86 ± 2.54
G2: 7.61 ± 3.04
G1/G2: P < 0.001
Trail Making Test
– part B score,
mean ± SD:
G1: 51.14 ± 15.19
G2: 66.43 ± 23.03
G1/G2: P < 0.001
Matching
Familiar Figures
Test score, mean
± SD:
Time of 1st
answer:
G1: 10.76 ± 4.30
G2: 15.96 ± 4.14
G1/G2: P < 0.001
Errors:
G1: 5.05 ± 1.47
G2: 8.04 ± 2.88
G1/G2: P < 0.001
Word fluency
test score, mean
± SD:
G1: 39.48 ± 0.87
G2: 39.26 ± 0.96
G1/G2: P = NS
Harms:
NR
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Golan et al., 2006
Study 1
Country:
UK
Enrollment
period:
NR
Funding:
National Alliance
for Autism
Research, Corob
Charitable Trust,
Cambridge
Overseas Trust,
B’nai B’rith Leo
Baeck, Shirley
Foundation,
Medical Research
Council, Three
Guineas Trust
Author industry
relationship
disclosures:
NR
Design:
Controlled study
Intervention:
Mind Reading computer
program used at home for
2 hr/wk over 10 weeks
Intervention target:
Emotion recognition skills
Primary outcome:
Emotion recognition
Groups:
G1: computer program
G2: no computer program
Treatment duration:
10-15 weeks
Frequency of contact
during study:
Beginning and end of
study, with 1 followup
phone call during the
study
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
Yes
Co-interventions held
stable during treatment:
Yes
Concomitant therapies:
NR
N at enrollment:
G1: 24
G2: 22
N at followup:
G1: 19
G2: 22
Inclusion criteria:
Diagnosed with AS/HFA in
specialist centers using
established criteria
No participation in any
related intervention
during the last 3 months
No plans for engaging in
another intervention
while the study was
ongoing
Exclusion criteria:
See inclusion criteria
Age, yrs, mean ± SD:
G1: 30.5 ± 10.3
G2: 30.9 ± 11.2
Mental age:
NR
Verbal IQ, mean ± SD:
G1: 108.3 ± 13.3
G2: 109.7 ± 10.0
Performance IQ, mean ±
SD:
G1: 112.0 ± 12.6
G2: 115.3 ± 12.3
Gender, n (%):
Male:
G1: 14 (74)
G2: 17 (73)
Female:
G1: 5 (26)
G2: 5 (23)
DSM-based diagnostic
approach reported:
No
AQ, mean ± SD
G1: 37.2 ± 8.4
G2: 38.2 ± 7.5
CAM score, mean
± SD:
Face mask:
G1: 31.3 ± 8.8
G2: 32.5 ± 8.4
Voice task:
G1: 33.8 ± 6.6
G2:35.2 ± 7.4
Number of concepts
recognized:
G1: 9.8 ± 5.2
G2: 10.5 ± 5.2
Reading the Mind
in the Eyes, mean
± SD:
G1: 23.1 ± 6.7
G2: 23.9 ± 6.7
Reading the Mind
in the Voice, mean
± SD:
G1: 16.1 ± 2.9
G2: 16.1 ± 3.9
Reading the Mind
in Films:
NR
CAM score,
mean ± SD:*
Face mask:
G1: 37.5 ± 7.8
G2: 36.6 ± 7.9
G1/G2: P < 0.002
Voice task:
G1: 38.9 ± 6.2
G2: 36.6 ± 7.9
G1/G2: P < 0.01
Number of
concepts
recognized:**
G1: 13.6 ± 4.8
G2: 11.3 ± 5.4
G1/G2: P < 0.01
Reading the
Mind in the Eyes,
mean ± SD:*
G1: 23.8 ± 4.7
G2: 23.0 ± 7.3
G1/G2: P = NS
Reading the
Mind in the
Voice, mean ±
SD:*
G1: 16.7 ± 3.9
G2: 17.4 ± 3.5
G1/G2: P = NS
Reading the
Mind in Films,
mean ± SD:*
G1: 11.8 ± 3.8
G2: 12.8 ± 3.4
G1/G2: P = NS
Harms:
NR
Comments:
Typical controls included in study as well but data not extracted.
* Significance is time X group interaction from a MANCOVA with covariates age, verbal, and performance IQ.
** ANOVA for CAM concepts showed significant individual between group effects for the following concepts: grave (P
< 0.05), lured (P < 0.05), uneasy (P < 0.05), intimate (P < 0.05), and nostalgic (P < 0.001) (data NR).
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Golan et al., 2006
Study 2
Country:
UK
Enrollment
period:
NR
Funding:
National Alliance
for Autism
Research, Corob
Charitable Trust,
Cambridge
Overseas Trust,
B’nai B’rith Leo
Baeck, Shirley
Foundation,
Medical Research
Council, Three
Guineas Trust
Author industry
relationship
disclosures:
NR
Design:
Prospective cohort
study
Intervention:
Computer program group:
Mind Reading computer
program 2 hr/wk for 10
weeks and 10 weekly
small group sessions with
a tutor
Social skills training: 10
weekly sessions of small
group social skills training
facilitated by a clinical
psychologist
Intervention target:
Emotion recognition skills
Primary outcome:
Emotion recognition
Groups:
G1: computer program
and tutor
G2: social skills training
Treatment duration:
10 weeks
Frequency of contact
during study:
Weekly
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
Yes
Concomitant therapies:
NR
N at enrollment:
G1: 18
G2: 18
N at followup:
G1: 13
G2: 13
Inclusion criteria:
Diagnosed with AS/HFA in
specialist centers using
established criteria
No participation in any
related intervention
during the last 3 months
Had no plans for engaging
in another intervention
while the study was
ongoing
Exclusion criteria:
See inclusion criteria
Age, yrs, mean ± SD:
G1: 25.5 ± 9.3
G2: 24.4 ± 6.4
Mental age:
NR
Verbal IQ, mean ± SD:
G1: 105.7 ± 16.1
G2: 96.5 ± 15.5
Performance IQ, mean ±
SD:
G1: 103.9 ± 19.8
G2: 95.5 ± 6.0
Gender, n (%):
Male:
G1: 12 (92)
G2: 10 (77)
Female:
G1: 1 (8)
G2: 3 (23)
DSM-based diagnostic
approach reported:
No
CAM scores, mean
± SD:
Face mask:
G1: 32.3 ± 8.1
G2: 26.8 ± 9.7
Voice task:
G1: 33.2 ± 9.1
G2: 31.1 ± 9.1
Number of concepts
recognized:
G1: 10.2 ± 4.9
G2: 7.7 ± 5.8
Reading the Mind
in the Eyes, mean
± SD:
G1: 21.6 ± 6.3
G2: 21.5 ± 5.6
Reading the Mind
in the Voice, mean
± SD:
G1: 15.1 ± 2.8
G2: 13.9 ± 4.5
Reading the Mind
in Films:
NR
CAM scores,
mean ± SD:*
Face mask:
G1: 36.2 ± 8.9
G2: 29.3 ±9.5
G1/G2: P = NS
Voice task:
G1: 38.9 ± 7.6
G2: 31.8 ± 10.9
G1/G2: P < 0.012
Number of
concepts
recognized:**
G1: 13.5 ± 5.2
G2: 8.5 ± 6.3
G1/G2: P < 0.016
Reading the
Mind in the Eyes,
mean ± SD:*
G1: 23.8 ± 4.2
G2: 19.2 ± 6.8
G1/G2: P < 0.01
Reading the
Mind in the
Voice, mean ±
SD:*
G1: 16.2 ± 3.5
G2: 14.7 ± 4.6
G1/G2: P = NS
Reading the
Mind in Films,
mean ± SD:
G1: 11.9 ± 3.7
G2: 10.5 ± 3.2
Harms:
NR
Comments:
* Significance is time X group interaction from a MANCOVA with covariate verbal IQ.
** ANOVA for CAM concepts showed significant individual between group effects for the following concepts: vibrant
(P < 0.05) and mortified (P < 0.01) (data NR).
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Hellings et al.,
2006
Country:
US
Enrollment
period:
NR
Funding:
NIH
Author industry
relationship
disclosures:
NR
Design:
Randomized
crossover study
Intervention:
Blinded phase:
Randomized subjects to
3, 4 or 5 weeks placebo;
then randomized to low or
high dose risperidone
phase; risperidone
gradually increased to
target dose over 2 weeks
then maintained for 4
weeks, then crossover to
other study arm; dose
then gradually tapered
down for 2 weeks,
followed by 3, 4 or 5 week
phase of placebo, then
open label phase for 24
weeks.
Low dose risperidone:
children and adolescents
1 mg/day; adults 2
mg/day
High dose risperidone:
children and adolescents
2.0 mg/day (range 1.2-2.9
mg/day); adults 3.6
mg/day (range 2.4-5.2
mg/day)
Open label phase:
optimal dose of
risperidone, adjusted
monthly as needed
Intervention target:
Persistent aggression,
property destruction and
self-injury
Primary outcome:
ABC-C Irritability subscale
score
Groups:
G1: all participants
Treatment duration:
46 weeks
Frequency of contact
during study:
Every second week and
at the end of each sub-
phase during the acute
phase; monthly during
the maintenance phase
Inclusion criteria:
Age 6-65 years
Mental retardation
(IQ < 70)
History of aggression,
property destruction or
self-injury = 6 months
by caregiver report
Baseline Irritability
subscale scores above
norms for age, gender
and setting as rated by
the primary caregiver
Drug-free period lasting =
2 weeks
Exclusion criteria:
Previous risperidone
hypersensitivity
History of neuroleptic
malignant syndrome
Seizures in past year
Degenerative brain disease
as assessed by history
Problematic living situation
such as lack of reliable
caregiving
Age, yrs, mean ± SD:
G1: 22 ± 13.1
Age, years, n:
8-12 (children):
G1: 13
13-18 (adolescents):
G1: 8
22-56 (adults):
G1: 19
Mental age:
NR
Gender, n (%):
Male:
G1: 23 (58)
Female:
G1: 17 (42)
DSM-based diagnostic
approach reported:
Yes
ABC-C subscale
scores, 1st placebo
period, mean ± SD:
Irritability:
G1: 19.16 ± 9.96
Lethargy:
G1: 7.61 ± 6.85
Stereotypy:
G1: 5.72 ± 5.63
Hyperactivity:
G1: 19.51 ± 11.10
Excessive speech:
G1: 4.42 ± 3.25
ABC-C subscale
scores, 2nd
placebo period,
mean ± SD:
Irritability:
G1: 18.22 ± 12.35
Lethargy:
G1: 7.04 ± 7.62
Stereotypy:
G1: 6.47 ± 6.84
Hyperactivity:
G1: 19.95 ± 15.05
Excessive speech:
G1: 3.97 ± 15.05
ABC-C Subscale
scores, low dose
phase, mean ±
SD:
Irritability:*
G1: 11.15 ± 9.28
Lethargy:
G1: 5.06 ± 5.96
Stereotypy:
G1: 4.07 ± 4.86
Hyperactivity:
G1: 12.79 ± 11.38
Excessive
speech:
G1: 3.11 ± 3.15
ABC-C Subscale
scores, high
dose phase,
mean ± SD:
Irritability:*
G1: 13.31 ± 8.91
Lethargy:
G1: 6.98 ± 6.36
Stereotypy:
G1: 5.14 ± 5.51
Hyperactivity:
G1: 14.59 ± 12.44
Excessive
speech:
G1: 3.35 ± 3.50
Harms, n:
Weight gain > 3.0
kg:
G1: 28/40
Sedation and
gastrointestinal
side effects:**
G1: 13/40
Seizure
(maintenance
phase):
G1: 1
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Hellings et al.,
2006 (continued)
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
All: 40
N at followup:
All: 33
Comments:
* ABC-C irritability scores across both acute drug phases were significantly different than placebo (P = 0.0002). The
pattern of results for the children and adolescents was similar (data only available in figures).
The linear decreasing trend in irritability scores across the maintenance phase approached significance (P = 0.09).
Age group was a significant predictor of mean irritability scores across the maintenance phase (P < 0.0001).
DISCUS scores in the acute drug phase was more significant versus the 1st placebo period (P = 0.052) than versus
the 2nd placebo period (P = 0.482).
NSEC side effects significant at the 0.05 level were: drowsiness, increased weight gain, appetite, too quiet, not
themselves, tremor, lack of spontaneity and nasal congestion.
** These side effects lead to study withdrawal for 6/13 subjects.
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Howlin et al., 2005
Country:
UK
Enrollment
period:
NA
Funding:
The National
Autistic Society,
UK Department for
Work and
Pensions, New
Deal for Disabled
People, Student
Support Service,
British Telecom
Author industry
relationship
disclosures:
NR
Design:
Retrospective
case series
See related study
Mawhood et al.,
1999
Intervention:
Supported employment
program
Intervention target:
Preparation for work and
obtaining employment
Primary outcome:
NR
Groups:
G1: Supported employ-
ment program participants
Ga: 1995-1996 (pilot)
Gb: 2003-2005
Treatment duration:
NR
Frequency of contact
during study:
NR
Last followup post-
treatment:
NR
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1a: 30
G1b: 117
N at followup:
G1a: 30
G1b: 89
Inclusion criteria:
Participation in supported
employment program
from 1995-2003
Exclusion criteria:
See inclusion criteria
Age, yrs, mean ± SD:
G1a: 31.1 ± 9.1
G1b: 31.4 ± 9.3
Mental age, Raven
nonverbal IQ, mean ± SD
(range):
G1a: 110.2 ± 17.6 (70-135)
G1b: 110.7 ± 19.5 (60-139)
Gender, male:female
ratio:
G1a: 9.0:1
G1b: 4.2:1
DSM-based diagnostic
approach reported:
Yes (20% of client
diagnoses confirmed with
ADI or ADI-R)
BPVS score, mean
± SD (range):
G1a: 94.7 ± 21.2
(41-127)
G1b: 121.6 ± 32.3
(48-160)
EOWPVT score,
mean ± SD (range):
G1a: 99.3 ± 19.1
(59-132)
G1b: 91.2 ± 16.1
(50-122)
Benefits received,
n:
Severe disability
allowance:
G1: 6
Income support:
G1: 26
Housing benefit:
G1: 37
Job seekers
allowance:
G1: 36
Incapacity benefit:
G1: 16
Council tax:
G1: 19
Tax credit:
G1: 1
Other:
G1: 6
Disability allowance:
G1: 37
Employed, n (%):
G1b: 31/89 (39)
Living
independently, n:
G1b: 25
Benefits
received, n:
Severe disability
allowance:
G1: 1
Income support:
G1: 7
Housing benefit:
G1: 11
Job seekers
allowance:
G1: 0
Incapacity benefit:
G1: 5
Council tax:
G1: 8
Tax credit:
G1: 9
Other:
G1: 2
Disability
allowance:
G1: 44
Employed, n (%):
G1b: 59/89 (66)
G1b/BL: P <
0.001
Living
independently,
n:
G1b: 34
Job satisfaction
and social
outcomes
among those
employed, n:
Generally
satisfied with job:
G1b: 50/59
Job lives up to
expectations:
G1b: 45/59
Satisfied with
work hours:
G1b: 47/59
Satisfied with pay:
G1b: 38/59
Liked boss:
G1b: 49/59
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Howlin et al., 2005
(continued)
Considered
supported
employment
program helpful:
G1b: 58/59
Could not have
managed without
supported
employment
program help:
G1b: 44/59
Get along with
colleagues:
G1b: 52/59
Made friendships
as a result of jobs:
G1b: 32/59
Meet with
colleagues
outside of work:
G1b: 7/59
Jobs found
meeting criteria
of 16+ hrs/week
for = 13 weeks, n
(%):
G1: 134/192 (70)
Classisfication
of jobs found, n
(%):*
Permanent
contracts:
G1: 107/185 (58)
Short-term
contracts:
G1: 12/185 (6)
Temporary:
G1: 66/185 (36)
Line managers
satisfaction with
supported
employment
program, n:
Satisfied with
service offered:
G1b: 50/63
No problems with
participants’ work
performance:
G1b: 26/63
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Howlin et al., 2005
(continued)
Experienced
some difficulties
with participants’
work
performance:
G1b: 37/63
Program helped
to address
performance
difficulties:
G1b: 61/63
Personally gained
from working with
supported
employment
program:
G1b: 51/63
Senior manager
or employers’
satisfaction with
supported
employment
program:
Very satisfied:
G1b: 47/61
Satisfied:
G1b: 13/61
Harms:
NR
Comments:
Data were collected on clients enrolled from April 1995 to March 2003; new data were collected for clients registered
between 2002 and 2003 and for area 3 were available for the years 2000-2003.
* Data missing for 7 of the 192 jobs found.
Among 19/30 participants in 1995-1996 who found jobs, 13 remained in permanent jobs in 2002-2003, and 2 had re-
enrolled with the supported employment program. Of the 11/30 not finding jobs in 1995-1996, 2 located employment
by 2002-2003, 1 acted as a volunteer, and 1 had re-enrolled with the supported employment program.
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Kaplan et al.,
2005
Country:
US
Enrollment
period:
2002 to 2003
Funding:
NR
Author industry
relationship
disclosures:
NA
Design:
Retrospective
case series
Intervention:
Music therapy in varying
group sizes; sessions
occurred in community
music school, suburban
satellite, group home
settings
Intervention target:
Behavioral/psychosocial
skills; language/
communication skills;
perceptual/motor skills;
cognitive skills; musical
skills; modifying
physiological responses
Primary outcome:
Specific to client
Groups:
G1: Music therapy
Treatment duration:
2 program years
Frequency of contact
during study:
NR
Last followup post-
treatment:
NR
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1: 40*
N at followup:
G1: 40
Inclusion criteria:
Children and adults with
ASD diagnosis receiving
music therapy
Exclusion criteria:
See inclusion criteria
Age, yrs, mean (range):
G1: 13.9 (2-49)
Mental age:
NR
Gender, n (%):
Male:
G1: 28 (70)
Female:
G1: 12 (30)
DSM-based diagnostic
approach reported:
No
NR
Met initial
objectives, %:
G1: 100
Met intermediate
objectives, %:
G1: 77
Met Intermediate
objectives, by
category, %:
Behavioral/psy-
chosocial skills:
G1: 74
Language/com-
munication skills:
G1: 74
Perceptual/motor
skills:
G1: 80
Cognitive skills:
G1: 100
Musical skills:
G1: 100
Generalization of
skills learned in
primary goal
areas to
nonmusic
therapy settings,
by category, %:
Behavioral/psychosocial:
G1: 14/16 (88)
Language/
communication:
G1: 9/9 (100)
Perceptual/motor:
G1: 1/2 (50)
Cognitive:
G1: 2/2 (100)
Musical:
G1: 1/1 (100)
Harms:
NR
Comments:
* If a client was served both years, each year with that client was treated separately in the data.
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
O’Connor et al.,
2004
Country:
Canada
Enrollment
period:
NR
Funding:
NR
Author industry
relationship
disclosures:
NR
Design:
Randomized trial
with crossover
design
Intervention:
In one session, students
read 5 passages written in
3 different procedural
facilitation styles (pre-
reading questions,
anaphoric cuing, and
cloze task) and one
control style.
Order and style randomly
varied (approximately 10
min/passage, including
1 passage in each facili-
tation style and 2 control
passages); experiments
took place at home (n=14)
or school (n=6).
Intervention target:
Comprehension of text
Primary outcome:
Comprehension of text
Groups:
G1: all participants
Treatment duration:
Single session
Frequency of contact
during study:
NA
Last followup post-
treatment:
Immediately post
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1: 20
N at followup:
G1: 20
Inclusion criteria:
Moderate to high levels of
decoding
Lower levels of reading
comprehension
Exclusion criteria:
See inclusion criteria
Age, yrs, mean ± SD:
G1: 15.11 ± 0.99
Mental age, Stanford-
Binet Intelligence, mean
± SD:
G1: 88.15 ± 16.06
Gender, n (%):
Male:
G1: 19 (95)
Female:
G1: 1 (5)
DSM-based diagnostic
approach reported:
Yes
Total Reading
Comprehension
score, mean ± SD;
Control passage 1:
G1: 12.79 ± 6.33
Control passage 2:
G1: 12.86 ± 6.27
Total Reading
Comprehension
score, mean ±
SD;
Anaphoric cuing
passage:
G1: 15.41 ± 6.28
G1/BL: P = 0.03
Prereading ques-
tions passage:
G1: 13.88 ± 5.47
G1/BL: P = 0.29
Cloze passage:
G1: 13.83 ± 5.14
G1/BL: P = 0.32
Improvement of
= 0.50 SD, score
vs. control, n:
Anaphoric cuing
passage:
G1:11
Prereading ques-
tions passage:
G1: 7
Cloze passage:
G1: 7
Harms:
NR
Comments:
Repeated measures ANOVA showed a significant effect of procedural facilitation (combined) vs. control (P = 0.05).
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Van Bourgondien
et al., 2003
Country:
US
Enrollment
period:
NR
Funding:
NIMH
Author industry
relationship
disclosures:
NR
Design:
Prospective
Cohort
Intervention:
Experimental treatment
program (combined
residential & vocational
training program) using
TEACCH psychoeduca-
tional model
Part-random, part-clinical/
administrative assignment
of subjects to the treat-
ment group; the remaining
participants were living in
one of three control
conditions: group homes
institutions or family home
Intervention target:
Family satisfaction,
measures of participant
skills & behaviors
Primary outcome:
NR
Groups:
G1: TEACCH-based
program
G2: Family home
G3: Group homes
G4: Institutions
Treatment duration:
24 hour programs
assessed 6 and 12
months after participants’
entry into TEACCH
program
Frequency of contact
during study:
4 time periods of 6 month
intervals
Last followup post-
treatment:
12 months after moving
into G1
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
No
Inclusion criteria:
• Adolescents and adults
with autism selected
from applicants to the
TEACCH-based
program*
Exclusion criteria:
• See inclusion criteria
Age, yrs, mean ± SD:
G1: 23.7 ± 4.4
G2: 26.6 ± 5.1
G3: 27.8 ± 8.5
G4: 21.5 ± 5.0
Mental age, functioning
in the moderate to
severe/ profound ranges
of mental retardation, %:
Total: 85
Gender, n:
Male:
G1: 6
G2: 8
G3: 8
G4: 4
Female:
G1: 0
G2: 2
G3: 2
G4: 2
DSM-based diagnostic
approach reported:
Yes (CARS)
CARS score, mean
± SD:
G1: 37.3 ± 5.3
G2: 35.6 ± 6.9
G3: 34.7 ± 3.9
G4: 37.2 ± 2.9
ERS score, mean ±
SD:
Communication:
G1: 3.0 ± 0.65
Structure:
G1: 2.58 ± 0.62
Socialization:
G1: 2.81 ± 0.76
Developmental:
G1: 3.00 ± 0.63
Behavior:
G1: 3.31 ± 0.38
Total:
G1: 3.09 ± 0.43
Aggression and/or
self-injury, n:
G1: 3/6
G2: 2/10
G3: 5/10
G4: 4/6
ERS score, time
4, mean ± SD:
Communication:
G1: 4.10 ± 0.37
G2: 2.57 ± 0.58
G3: 2.74 ± 0.76
G4: 2.20 ± 0.72
G1/G2/G3/G4: P
= 0.0003
G1/G2: P < 0.05
G1/G3: P < 0.05
G1/G4: P < 0.05
G1/BL: P =
0.0003
Structure:
G1: 4.14 ± 0.29
G2: 2.20 ± 0.57
G3: 2.69 ± 0.41
G4: 2.28 ± 0.10
G1/G2/G3/G4: P
= 0.0001
G1/G2: P < 0.05
G1/G3: P < 0.05
G1/G4: P < 0.05
G1/BL: P =
0.0002
Socialization:
G1: 3.78 ± 0.53
G2: 2.40 ± 0.80
G3: 2.76 ± 0.69
G4: 2.33 ± 0.73
G1/G2/G3/G4: P
= 0.0057
G1/G2: P < 0.05
G1/G3: P < 0.05
G1/G4: P < 0.05
G1/BL: P =
0.0014
Developmental:
G1: 4.12 ± 0.24
G2: 2.68 ± 0.84
G3: 3.20 ± 0.48
G4: 2.50 ± 0.33
G1/G2/G3/G4: P
= 0.0025
G1/G2: P < 0.05
G1/G3: P = NS
G1/G4: P < 0.05
G1/BL: P =
0.0006
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Van Bourgondien
et al., 2003
(continued)
Concomitant therapies:
Receiving at-least one
medication for behavioral
control, %:
Total: 53
Behavior control medica-
tions, mean ± SD:
G1: 1.5 ± 1.4
G2: 0.3 ± 0.5
G3: 1.4 ± 2.0
G4: 1.7 ± 2.0
N at enrollment:
G1: 6
G2: 10
G3: 10
G4: 6
N at followup:
G1: 6
G2: 10
G3: 10
G4: 6
Behavior:
G1: 4.43 ± 0.37
G2: 2.29 ± 0.76
G3: 2.8 ± 0.32
G4: 2.71 ± 0.38
G1/G2/G3/G4: P
= 0.0001
G1/G2: P < 0.05
G1/G3: P < 0.05
G1/G4: P < 0.05
G1/BL: P =
0.0001
Total:
G1: 4.11 ± 0.31
G2: 2.67 ± 0.60
G3: 3.04 ± 0.34
G4: 2.85 ± 0.35
G1/G2/G3/G4: P
= 0.0001
G1/G2: P < 0.05
G1/G3: P < 0.05
G1/G4: P < 0.05
G1/BL: P =
0.0001
Global ratings,
mean ± SD:
Programming:
G1: 5.00 ± 0.00
G2: 2.25 ± 0.89
G3: 3.00 ± 1.10
G4: 2.60 ± 0.89
G1/G2/G3/G4: P
= 0.0001
G1/G2: P < 0.05
G1/G3: P < 0.05
G1/G4: P < 0.05
Desirability:
G1: 135.83 ± 4.02
G2: 69.13 ± 25.89
G3: 75.36 ± 35.28
G4: 33.6 ± 24.2
G1/G2/G3/G4: P
= 0.0001
G1/G2: P < 0.05
G1/G3: P < 0.05
G1/G4: P < 0.05
G2/G3: P = NS
G2/G4: P < 0.05
G3/G4: P < 0.05
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Van Bourgondien
et al., 2003
(continued)
Family satis-
faction survey,
community
involvement,
mean ± SD:
G1: 5.0 ± 0.0
(n=5)
G3: 3.10 ± 1.44
(n=3)
G4: 3.33 ± 0.58
(n=10)
G1/G3: P < 0.05
G1/G4: P = 0.13
Skills index,
mean ± SD:
G1: 3.5 ± 1.5
G2: 3.3 ± 2.1
G3: 3.1 ± 2.1
G4: 2.6 ± 1.8
Index of negative
behaviors, mean
± SD:
G1: 1.8 ± 0.3
G2: 1.4 ± 0.6
G3: 1.6 ± 0.5
G4: 1.6 ± 0.6
G1/G2: P = 0.05
Negative
behavior
observations,
mean ± SD:
G1: 16.8 ± 6.8
G2: 20.4 ± 11.7
G3: 16.0 ± 12.8
G4: 24.2 ± 12.5
Negative
behavior
observations
without stereo-
typies, mean ±
SD:
G1: 0.7 ± 0.6
G2: 4.2 ± 5.8
G3: 2.0 ± 2.3
G4: 6.5 ± 9.0
Harms:
NR
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Garcia-Villamisar
et al., 2000†,
2002*
Country:
Spain, Germany
Enrollment
period:
1996-2000†*
Funding:
Horizon Program
of European
Union, Cosejería
de Asuntos
Sociales de la
Comunidad
Autónoma de
Madrid (Spain)
Author industry
relationship
disclosures:
NR
Design:
Nonrandomized
controlled trial
Intervention:
Sheltered and supported
community-based work
environments*
Intervention target:
To analyze the differential
impact of two modalities
of work on clinical
symptom evolution
between 1996 & 1999†
Groups:
G1: Sheltered work group
(SHW)†*
G2: Supported work
group (SPW)†*
Primary outcome:
NR
Treatment duration:
Average length of
community employment:
30 months for an average
of 20 hours/week
Frequency of contact
during study:
Beginning and end of
program
Last followup post-
treatment:
Immediately post-
treatment†
5 years from start of
program*
Measure of treatment
fidelity/adherence
reported:
Co-interventions held
stable during treatment:
Concomitant therapies:
NR
N at enrollment:
G1: 26
G2: 25
N at followup:
G1: 26
G2: 21
Inclusion criteria:
• Diagnosis of autism
• Provision of informed
consent
• For G2, sheltered
workshop enrollment
prior to participation in
supported work, no
severe behavior
problems, acceptable
professional and
vocational abilities
Exclusion criteria:
• See inclusion
Age, yrs, mean ± SD:
G1: 21.07 ± 4.18
G2: 21.64 ± 3.75
IQ, Leiter (total score),
mean ± SD:
G1: 55.52 ± 14.43
G2: 57.41 ± 15.01
Gender, n:
Male:
G1: 18
G2: 21
Female:
G1: 8
G2: 4
DSM-based diagnostic
approach reported:
• Yes (DSM-IV & CARS)
QoL QNR score,
mean ± SD:*
Environmental
control:
G1: 10.00 ± 2.23
G2: 10.80 ± 2.50
G1/G2: P = NS
Community
involvement:
G1: 11.88 ± 3.01
G2: 13.28 ± 3.22
G1/G2: P = NS
Perception of
personal change:
G1: 7.50 ± 1.03
G2: 8.00 ± 0.93
G1/G2: P = NS
Total Score:
G1: 29.53 ± 5.26
G2: 31.40 ± 6.94
G1/G2: P = NS
CARS score, mean
± SD:†
G1: 35.26 ± 6.51
G2: 32.23 ± 8.59
QoL QNR score,
mean ± SD:*
Environmental
control:
G1: 10.82 ± 2.26
G2: 13.04 ± 2.03
G1/G2: P < 0.002
G2/BL: P < 0.001
Community
Involvement :
G1: 12.35 ± 3.01
G2: 14.04 ± 1.71
G1/G2: P < 0.01
G2/BL: P = 0.187
Perception of
Personal Change:
G1: 7.62 ± 1.62
G2: 8.95 ± 1.30
G1/G2: P < 0.008
G2/BL: P < 0.007
Total score:
G1: 30.76 ± 5.51
G2: 35.96 ± 3.43
G1/G2: P <
0.0001
G2/BL: P < 0.001
CARS score,
mean ± SD:†
G1: 38.26 ±7.40
G2: 32.19 ± 7.26
G1/BL: P < 0.006
G2/BL: P = 0.71
Harms:
NR
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Remington et al.,
2001
Country:
Canada
Enrollment
period:
NR
Funding:
Ontario Mental
Health Foundation
Author industry
relationship
disclosures:
NR
Design:
Double blind,
placebo controlled
randomized
crossover design
Intervention:
Clomipramine: 25 mg at
bedtime for 2 days, 25 mg
2 times/day for 2 days, 25
mg 3 times/day for 2
days, and 50 mg twice a
day; doses then increased
in 25 mg increments
every 3-4 days as clini-
cally indicated; planned
treatment period: 7 weeks
(actual mean 4.5 weeks)
Haloperidol: 0.25 mg at
bedtime for 2 days, 0.25
mg 2 times/day for 2
days, 0.25 mg 3 times/day
for 2 days, and 0.5 mg
twice a day; doses then
increased in 0.5 mg
increments every 3- 4
days as clinically indi-
cated; planned treatment
period: 7 weeks (actual
mean 5.8 weeks)
Placebo: planned
treatment period: 7 weeks
(actual mean 5.4 weeks);
placebo also administered
for 1 week before first
phase and between each
treatment phase
Intervention target:
Treatment of autistic
disorder
Primary outcome:
NR
Groups:
G1: study participants
G1a: clomipramine phase
G1b: haloperidol phase
G1c: placebo phase
Treatment duration:
Each phase 7 weeks
(total 21 weeks)
Frequency of contact
during study:
Every two weeks
Last followup post-
treatment:
Immediately post-
treatment
Inclusion criteria:
• DSM-IV diagnosis of
autism confirmed
independently by two
investigators
• A recommendation
based on initial
assessment of
pharmacotherapy
• Evidence haloperidol or
clomipramine had not
been used previously
• If haloperidol or
clomipramine had been
used previously, an
adequate therapeutic
trial was not completed
Exclusion criteria:
• See inclusion criteria
Age, yrs, mean (range):
G1: 16.3 (10-36)
Mental age:
NR
Gender, n (%):
Male:
G1: 30 (83.3)
Female:
G1: 6 (16.7)
DSM-based diagnostic
approach reported:
Yes
CARS score, mean
± SD:
G1: 41.8 ± 7.1
DOTES score,
mean ± SD:
G1: 0.6 ± 2.2
ESRS score, mean
± SD:
G1: 6.6 ± 6.7
ABC score, mean:
Irritability:
G1: NR*
Lethargy:
G1: NR*
Stereotypy:
G1: NR*
Hyperactivity:
G1: NR*
Inappropriate
speech:
G1: NR*
CARS score,
mean ± SD:
G1a: 37.8 ± 8.7
G1b: 36.7 ± 6.1
G1c: 39.4 ± 7.0
G1a/G1b/G1c:
P = 0.05
G1a/BL: P = NS
G1b/BL: P < 0.05
G1c/BL: P = NS
DOTES score,
mean ± SD:
G1a: 2.0 ± 2.9
G1b: 2.3 ± 3.3
G1c: 0.8 ± 1.7
G1a/G1b/G1c:
P = NS
ESRS score,
mean ± SD:
G1a: 10.3 ± 7.3
G1b: 7.8 ± 5.8
G1c: 7.9 ± 7.1
G1a/G1b/G1c:
P = NS
ABC score,
mean:
Irritability:
G1a: NR*
G1b: NR*
G1c: NR*
G1a/G1b/G1c:
P = 0.03
G1a/BL: P = NS
G1b/BL: P < 0.05
G1c/BL: P = NS
Lethargy:
G1a: NR*
G1b: NR*
G1c: NR*
G1a/G1b/G1c:
P = NS
Stereotypy:
G1a: NR*
G1b: NR*
G1c: NR*
G1a/G1b/G1c:
P = NS
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Remington et al.,
2001 (continued)
Measure of treatment
fidelity/adherence
reported:
Yes
Co-interventions held
stable during treatment:
Yes
Concomitant therapies:
NR
N at enrollment:
G1a: 32
G1b: 33
G1c: 32
N at followup:
G1a: 12
G1b: 23
G1c: 21
G1a/G1b/G1c: P < 0.001
Hyperactivity:
G1a: NR*
G1b: NR*
G1c: NR*
G1a/G1b/G1c:
P = 0.01
G1a/BL: P = NS
G1b/BL: P < 0.05
G1c/BL: P = NS
Inappropriate
speech:
G1a: NR*
G1b: NR*
G1c: NR*
G1a/G1b/G1c:
P = NS
Harms:
Discontinued
early due to
behavioral
problems only:
G1a: 8
G1b: 3
G1c: 10
Discontinued
early due to
physiologic effects
and behavioral
problems:
G1a: 4
G1b: 1
G1c: 0
Discontinued
early due to
physiologic effects
only:
G1a: 8
G1b: 6
G1c: 1
Fatigue or
lethargy:
G1a: 4
G1b: 5
G1c: 0
Tremors:
G1a: 2
G1b: 0
G1c: 0
Tachycardia:
G1a: 1
G1b: 0
G1c: 0
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Remington et al.,
2001 (continued)
Insomnia:
G1a: 1
G1b: 0
G1c: 0
Diaphoresis:
G1a: 1
G1b: 0
G1c: 0
Nausea or
vomiting:
G1a: 1
G1b: 0
G1c: 0
Decreased
appetite:
G1a: 1
G1b: 0
G1c: 0
Preexisting right
bundle branch
block:
G1a: 1
G1b: 0
G1c: 0
Dystonia:
G1a: 0
G1b: 1
G1c: 0
Depression:
G1a: 0
G1b: 1
G1c: 1
Persistent
nosebleeds:
G1a: 0
G1b: 0
G1c: 1
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Silver et al.,
2001
Country:
UK
Enrollment
period:
NR
Funding:
NR
Author industry
relationship
disclosures:
NA
Design:
RCT
Intervention:
School-based Emotion
Trainer computer inter-
vention, 10 daily half hour
computer sessions (used
mean 8.4 times, range 2-
15 times)
Intervention target:
Better recognition and
prediction of emotional
responses in others
Primary outcome:
NR
Groups:
G1: computer sessions
and standard lessons
G2: standard lessons only
Treatment duration:
2-3 weeks
Frequency of contact
during study:
Daily during school
Last followup post-
treatment:
End of treatment
Measure of treatment
fidelity/adherence
reported:
Yes
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1: 12
G2: 12
N at followup:
G1: 10
G2: 11
Inclusion criteria:
Clear diagnosis of autistic
spectrum disorder
Age equivalent = 7 years
on the British Picture
Vocabulary Scale
Chronological age 10-18
Exclusion criteria:
See inclusion criteria
Age, yrs, mean ± SD:*
G1: 13.9 ± 0.9
G2: 14.75 ± 2.0
Mental age, BPVS age
equivalent, yrs, mean ±
SD:
G1: 10.67 ± 2.25
G2: 12.0 ± 3.33
Gender:
NR
DSM-based diagnostic
approach reported:
No
Facial Expression
Photographs, total
error score, mean
± SD:
G1: 4.27 ± 1.85
G2: 4.45 ± 2.34
Emotion
Recognition
Cartoons, total
error score, mean
± SD:
G1: 4.36 ± 3.35
G2: 3.27 ± 1.79
Strange Stories,
compound Likert
score, mean ± SD:
G1: 18.3 ± 16.4
G2: 20.8 ± 22.9
Facial
Expression
Photographs,
total error score,
mean:
G1: NR**
G2: NR**
ANOVA: group X
time P = NS; time
P = 0.029
Emotion
Recognition
Cartoons, total
error score,
mean:
G1: NR**
G2: NR**
ANOVA: group X
time P = 0.041
Strange Stories,
compound Likert
score, mean:
G1: NR**
G2: NR**
ANOVA: group X
time P = 0.016
Harms:
NR
Comments:
* Chronological age means and SD converted from years/months to years
** Values are only represented graphically.
The teaching tasks were computer based and the assessment tasks were paper based.
The number of times a child used the computer program significantly correlated with an improvement in score on the
Emotion Recognition Cartoons and the Strange Stories but not with improvement on the Facial Expression
Photographs.
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Mawhood et al.,
1999
Country:
UK
Enrollment
period:
NR
Funding:
Nuffield
Foundation,
Department of
Employment,
National Autistic
Society
Author industry
relationship
disclosures:
NR
Design:
Prospective cohort
study
Intervention:
Supported employment
scheme: upon suitable job
identification, full time
support worker provided
for 1st 2-4 weeks; support
decreased to 1-2 times/
week during the 2nd
month; further reduction
in support so by the 4th
month, occasional
planned meetings (a
support worker could be
contacted anytime during
an emergency)
Intervention target:
Employment
Primary outcome:
Employment
Groups:
G1: supported
employment scheme
G2: no employment
support
Treatment duration:
2 years (mean ± SD
17.03 ± 6.64 months)
Frequency of contact
during study:
Daily for 2-4 weeks, then
1-2 times/week during 2nd
month, then occasional
meetings during 4th month
Last followup post-
treatment:
Immediately post
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
Inclusion criteria:
Formal diagnosis of autism
or Asperger syndrome
IQ = 70 on either WAIS
performance or verbal
scale
Actively seeking work
Able to travel indepen-
dently and prepared to
work within the greater
London area (G1) or
outside greater London
area (G2)
Capable of eventually
maintaining employment
with minimal support
No additional psychiatric or
physical problems that
would adversely affect
employability
Exclusion criteria:
See inclusion criteria
Age, yrs, mean ± SD:
G1: 31.1 ± 9.1
G2: 28.0 ± 6.1
Mental age, mean ± SD:
WORD reading accuracy
test:
G1: 16.6 ± 1.5
G2: NR
WORD comprehension
test:
G1: 13.8 ± 3.6
G2: NR
WORD spelling test:
G1: 16.2 ± 2.1
G2: NR
British Ability Scales
Number subtest
G1: 12.9 ± 1.8
G2: NR
IQ, mean ± SD:
WAIS verbal IQ:
G1: 104.1 ± 17.3
G2: 101.6 ± 0.50
WAIS performance IQ:
G1: 91.6 ± 15.7
G2: 92.2 ± 0.12
Employed, n:
G1: 8
G2: 3
Time in work, %
(range):
G1: 18.58 (0-100)
G2: 10.79 (0-100)
G1/G2: P = 0.35
Rosenberg Self-
Esteem Inventory
score, mean ± SD:
G1: 21.79 ± 4.78
G2: 21.50 ± 4.43
Employed, n (%):
G1: 19 (63.3)
G2: 5 (25)
G1/BL: P = 0.009
G2/BL: P = 0.69
G1+G2/BL: P =
0.01
Employment, n:
Permanent jobs:
G1: 9
G2: 3
Temporary/
seasonal jobs:
G1: 10
G2: 2
Time to find
employment,
months, mean
(range):
G1: 8.7 (6-23)
G2: 8.4 (3-16)
Hours worked/
week, mean
(range):
G1: 31.3 (16-
38.75)
G2: 36.5 (35-40)
G1/G2: P = 0.506
Wages/hour, £,
mean (range):
G1: 5.71 (3.71-
9.49)
G2: 4.14 (3.83-
4.5)
G1/G2: P = 0.024
Type of jobs
found, n:
Administrative/
clerical:
G1: 16
G2: 1
Computing:
G1: 2
G2: 0
Photography
laboratory:
G1: 1
G2: 0
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Mawhood et al.,
1999 (continued)
N at enrollment:
G1: 30
G2: 20
N at followup:
G1: 30
G2: 17
WAIS full-scale IQ:
G1: 98.8 ± 16.3
G2: 97.7 ± 0.22
BPVS:
G1: 94.7 ± 21.2
G2: 91.8 ± 0.46
EOWPVT:
G1: 99.3 ± 19.1
G2: 98.6 ± 0.13
Gender, n:
Male:
G1: 27
G2: 20
Female:
G1: 3
G2: 0
DSM-based diagnostic
approach reported:
No
Sales support:
G1: 1
G2: 0
Warehouse/
factory:
G1: 2
G2: 1
Postman/messen-
ger/outdoor:
G1: 0
G2: 3
Time in work, %
(range):
G1: 26.81 (0-
87.5) (n=26)
G2: 7.61 (0-82.3)
(n=17)
G1/BL: P = 0.22
G2/BL: P = 0.91
G1+G2/BL: P =
0.02
Rosenberg Self-
Esteem
Inventory score,
mean ± SD:
G1: 22.08 ± 4.00
G2: 22.25 ± 5.12
Harms:
NR
Comments:
More individuals in the control group (10% vs. 3%) had attended special needs courses (P = NS).
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes**
Author:
McDougle et al.,
1998
Country:
US
Enrollment
period:
June 1994 to
February 1997
Funding:
Public Health
Service, National
Alliance for
Research in
Schizophrenia and
Depression,
Theodore and
Vada Stanley
Foundation,
Connecticut
Department
of Mental Health
and Addiction
Services,
Research Unit on
Pediatric Psycho-
pharmacology
(RUPP), NIMH
Author industry
relationship
disclosures:
NR
Design:
RCT, double blind;
subsequent open
label trial
Intervention:
Risperidone starting at
1 mg/day, gradually
increasing by 1 mg daily
every 3-4 days to a
maximum dosage of 10
mg/day, twice daily as
tolerated for at least 7
weeks. Those treated with
placebo subsequently
given a 12 week open
label trial of risperidone.
Intervention target:
CGI global Improvement,
repetitive behavior,
aggression, sensory
motor behaviors, social
relationship to people,
affectual reactions,
sensory responses,
language, overall
behavioral symptoms of
autism and mood states
Primary outcome:
NR
Groups:
G1: risperidone
G2: placebo
G2a: open label trial of
risperidone
Daily dose, mean ± SD:
G1: 2.9 ± 1.4
G2: 3.9 ± 1.5
Treatment duration:
12 weeks
Frequency of contact
during study:
Baseline, end of weeks 4,
8, and 12
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
NA
Co-interventions held
stable during treatment:
Yes
Inclusion criteria:
Diagnosis of autism or
PDD-NOS
Moderate CGI scores
Y-BOCS compulsion
(repetitive behavior)
subscale score > 10
SIB-Q score = 25
Ritvo-Freeman Real-life
Rating Scale overall
score = 0.20
Exclusion criteria:
Met DSM-IV criteria for
schizophrenia or had
psychotic symptoms
Significant acute medical
condition
Age, yrs, mean ± SD:
G1: 26.0 ± 6.7
G2: 29.7 ± 7.8
Mental age, full scale IQ,
mean ± SD:
G1: 55.5 ± 26.8
G2: 52.9 ± 22.1
Gender, n:
Male:
G1: 13
G2: 9
Female:
G1: 2
G2: 7
DSM-based diagnostic
approach reported:
Yes (DSM-IV, ADOS, ADI)
CGI scale score,
mean (SE):
G1: 4 (0)
G2: 4 (0)
G2a: 4 (0)
Modified Y-BOCS
score, mean (SE):
G1:16.15 (3.58)
G2:14.29 (3.50)
G2a: 14.27 (2.92)
SIB-Q total score,
mean (SE):
G1: 47.8 (19.5)
G2: 37.7 (11.9)
G2a: 32.43 (15.89)
Ritvo-Freeman
subscale score,
mean (SE):
Sensory motor
behaviors:
G1: 0.79 (0.65)
G2: 0.71 (0.58)
G2a: 0.68 (0.48)
Social relationship
to people:
G1: NR
G2: NR
G2a: NR
Affectual reactions:
G1: 1.02 (0.39)
G2: 0.78 (0.49)
G2a: 0.75 (0.53)
Sensory responses:
G1: NR
G2: NR
G2a: 0.70 (0.38)
Language:
G1: NR
G2: NR
G2a: NR
Ritvo-Freeman
overall behavioral
symptom score,
mean (SE):
G1: 0.60 (0.44)
G2: 0.53 (0.41)
G2a: 0.50 (0.38)
CGI scale score,
12 weeks, mean
(SE):
G1: 2.54 (1.27)
G2: 4 (0.79)
G2a: 2.47 (1.06)
G1/G2: P < 0.001
G2a/BL: P <
0.001
Responders (CGI
much improved
or very much
improved), n (%):
G1: 8/14 (57)
G2: 0
G2a: 9/15 (60)
Modified Y-
BOCS score, 12
weeks, mean
(SE):
G1: 12.77 (3.63)
G2: 14.35 (3.02)
G2a: 11.47 (3.64)
G1/G2: P < 0.02
G2a/BL: P < 0.03
SIB-Q total
score, 12 weeks,
mean (SE):
G1: 24.2 (9.5)
G2: 32.8 (15.0)
G2a: 23.07
(13.45)
G1/G2: P < 0.01
G2a/BL: P < 0.05
Ritvo-Freeman
subscale score,
12 weeks, mean
(SE):
Sensory motor
behaviors:
G1: 0.38 (0.38)
G2: 0.64 (0.49)
G2a: 0.44 (0.31)
G1/G2: P < 0.007
G2a/BL: P < 0.04
Social relation-
ship to people:
G1: NR
G2: NR
G2a: NR
G1/G2: P = NS
G2a/BL: P = NS
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes**
McDougle et al.,
1998 (continued)
Concomitant therapies,
n:
Chloral hydrate (2 g/day)
for agitation: NR
N at enrollment:
G1:15
G2: 16
G2a: 16
N at followup:*
G1: 12
G2: 12
G2a: 15
VAS mood scores,
clinician rated,
mean (SE):
Anxious or nervous:
G1: 70.4 (16.4)
G2: 66.6 (22.1)
G2a: 62.67 (26.04)
Depressed:
G1: 23.8 (17.6)
G2: 23.1 (28.1)
G2a: NR
Irritable:
G1: 51.8 (23.2)
G2: 31.5 (24.4)
G2a: 27.33 (23.75)
Calm:
G1: NR
G2: NR
G2a: 26.67 (22.25)
Restless:
G1: NR
G2: NR
G2a: 54.67 (28.25)
Affectual
reactions:
G1: 0.35 (0.37)
G2: 0.82 (0.57)
G2a: 0.33 (0.28)
G1/G2: P < 0.003
G2a/BL: P <
0.007
Sensory
responses:
G1: NR
G2: NR
G2a: 0.44 (0.36)
G1/G2: P = NS
(P < 0.02; n=24)
G2a/BL: P <
0.004
Language:
G1: NR
G2: NR
G2a: NR
G1/G2: P = NS
G2a/BL: P = NS
Ritvo-Freeman
overall
behavioral
symptom score,
12 months, mean
(SE):
G1: 0.32 (0.27)
G2: 0.45 (0.41)
G2a: 0.27 (0.33)
G1/G2: P < 0.05
G2a/BL: P <
0.003
VAS mood
scores, 12
months, clinician
rated, mean
(SE):***
Anxious or
nervous:
G1: 42.3 (28.0)
G2: 60.0 (28.5)
G1/G2: P < 0.02
(P < 0.03; n=24)
G2a: 37.93
(29.95)
G2a/BL: P < 0.02
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes**
McDougle et al.,
1998 (continued)
Depressed:
G1: 8.5 (11.4)
G2: 19.4 (25.4)
G2a: NR
G1/G2: P < 0.03
(P < 0.08; n=24)
G2a/BL: P = NS
Irritable:
G1: 21.8 (20.4)
G2: 22.3 (24.9)
G1/G2: P < 0.01
G2a: 14.13
(16.27)
G2a/BL: P < 0.05
Calm:
G1: NR
G2: NR
G2a: 46.60
(24.01)
G1/G2: P = NS
G2a/BL: P < 0.01
Restless:
G1: NR
G2: NR
G2a: 27.00
(22.82)
G1/G2: P = NS
G2a/BL: P < 0.03
Harms:
At least one
adverse event, n
(%):
G1: 13/15 (87)
G2: 5/16 (31)
Sedation:
G1: 9
G2: 0
Agitation:
G1: 2
G2: 5
Enuresis:
G1: 2
G2: 0
Weight gain:
G1: 2
G2: 0
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes**
McDougle et al.,
1998 (continued)
Dyspepsia,
diarrhea,
constipation:
G1: 1
G2: 0
Abnormal gait,
G1: 1
G2: 0
Comments:
* 24/31 completed the entire 12 week study; of these 14/24 were 13-30 years old (G1: 8; G2: 6). 7/31 completed only
1-4 weeks of treatment; of these 5/7 were 13-30 years old (G1: 2; G2: 3).
** Where available, P-values reported for drug X time interaction are from ANCOVAs using baseline and 12-week
values; P-values reported for VAS are from 2-way ANOVAs with repeated measures for all patients that completed at
least 4 weeks (n=30; ITT analysis) and for completers (n=24). The latter value was also included if only one of the
tests was significant. P-values reported for the open label trial from 1-way ANOVA with repeated measures.
*** No other significant difference over time reported for any of the other mood measures.
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
McDougle et al.,
1998
Country:
US
Enrollment
period:
NR
Funding:
Pfizer, NIH,
National Alliance
for Research on
Schizophrenia and
Depression,
Theodore and
Vada Stanley
Research
Foundation,
Connecticut
Department of
Mental Health and
Addiction Services
Author industry
relationship
disclosures:
NR
Design:
Prospective case
series
Intervention:
Sertraline, started at 50
mg/day with further
increases of 50 mg/day
every week (maximum
200 mg/day as tolerated,
attained within 3 weeks).
Actual dose, mg, mean ±
SD (range): 122.0 ± 60.5
(50-200)
Intervention target:
Reduced repetitive
thoughts/behavior and
aggression; enhancement
of social relatedness
Primary outcome:
NR
Groups:
G1: sertraline
Ga: autistic disorder
Gb: Asperger’s disorder
Gc: PPD NOS
Treatment duration:
12 weeks
Frequency of contact
during study:
0, 4, 8 and 12 weeks
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies,
n:*
1000-3000 mg chloral
hydrate: 4
N at enrollment:
G1: 42
G1a: 22
G1b: 6
G1c: 14
N at followup:
G1: 37
Inclusion criteria:
DSM-IV diagnosis of ASD
Y-BOCS score > 15 (verbal
patients) or > 7
(nonverbal patients)
S-IBQ score = 25
Ritvo-Freeman Real-Life
rating scale overall score
= 0.20 or VABS
Maladaptive Behavior
subscale part 1 score =
14 or VABS Maladaptive
Behavior subscale part 2
score = 5
Psychotropic drug-free for
= 4 weeks before start
of trial
Exclusion criteria:
DSM-IV diagnosis of
psychotic or bipolar
disorder
Significant medical
problem (e.g., seizure)
Age, yrs, mean ± SD:
G1: 26.1 ± 5.8
Mental age:
NR
IQ, mean ± SD:
G1: 60.5 ± 22.7
Gender, n (%):
Male:
G1: 27 (64)
Female:
G1: 15 (36)
DSM-based diagnostic
approach reported:
Yes
CGI scale score,
mean ± SD:
G1a: NA
G1b: NA
G1c: NA
Y-BOCS score,
mean ± SD:
Total:
G1a: 16.5 ± 6.7
G1b: 25.7 ± 41.1
G1c: 18.2 ± 4.8
Obsession
subscale:
G1a: 2.6 ± 5.1
G1b: 12.5 ± 2.7
G1c: 4.2 ± 5.7
Compulsion
subscale:
G1a: 13.9 ± 4.1
G1b: 13.2 ± 2.7
G1c: 14.0 ± 3.6
SIB-Q total score,
mean ± SD:
G1a: 32.7 ± 16.5
G1b: 17.5 ± 7.7
G1c: 36.2 ± 16.4
Ritvo-Freeman
behavioral
symptom score,
mean ± SD:
Overall:
G1a: 0.48 ± 0.49
G1b: 0.26 ± 0.38
G1c: 0.77 ± 0.53
Subscale I:
G1a: 0.71 ± 0.59
G1b: 0.33 ± 0.20
G1c: 0.71 ± 0.52
Subscale II:
G1a: 0.21 ± 0.72
G1b: -0.17 ± 0.45
G1c: 0.42 ± 0.57
Subscale III:
G1a: 0.81 ± 0.52
G1b: 0.40 ± 0.28
G1c: 1.12 ± 0.56
Subscale IV:
G1a: 0.71 ± 0.52
G1b: 0.66 ± 0.59
G1c: 0.88 ± 0.53
CGI scale score,
12 weeks, mean
± SD:
G1a: 2.1 ± 1.0
G1b: 4.0 ± 0.0
G1c: 2.3 ± 0.9
G1/BL: P =
0.0001
Responders (CGI
much improved
or very much
improved), n (%):
G1: 24 (57)
G1a: 15 (68)
G1b: 0
G1c: 9 (64)
Y-BOCS score,
12 weeks, mean
± SD:
Total:
G1a: 11.5 ± 5.8
G1b: 27.8 ± 5.3
G1c: 14.8 ± 5.7
G1/BL: P = 0.005
Obsession
subscale:
G1a: 2.2 ± 4.2
G1b: 13.8 ± 3.0
G1c: 3.8 ± 5.2
G1/BL: P = NS
Compulsion
subscale:
G1a: 9.3 ± 3.8
G1b: 14.0 ± 3.6
G1c: 11.0 ± 3.3
G1/BL: P =
0.0001
SIB-Q total
score, 12 weeks,
mean ± SD:
G1a: 15.5 ± 9.5
G1b: 18.8 ± 7.7
G1c: 20.2 ± 12.8
G1/BL: P =
0.0001
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
McDougle et al.,
1998 (continued)
Subscale V:
G1a: -0.02 ± 0.53
G1b: -0.50 ± 0.30
G1c: 0.15 ± 0.51
VABS Maladaptive
Behavior
subscales score,
mean ± SD:
G1a: 27.0 ± 9.4
G1b: 19.8 ± 8.6
G1c: 28.3 ± 10.8
Ritvo-Freeman
behavioral
symptom score,
12 weeks, mean
± SD:
Overall:
G1a: 0.17 ± 0.29
G1b: 0.29 ± 0.36
G1c: 0.33 ± 0.33
G1/BL: P =
0.0001
Subscale I:
G1a: 0.40 ± 0.33
G1b: 0.33 ± 0.20
G1c: 0.37 ± 0.33
G1/BL: P = 0.001
Subscale II:
G1a: -0.10 ± 0.53
G1b: 0.02 ± 0.26
G1c: 0.15 ± 0.49
G1/BL: P = NS
Subscale III:
G1a: 0.38 ± 0.25
G1b: 0.37 ± 0.32
G1c: 0.61 ± 0.49
G1/BL: P = 0.001
Subscale IV:
G1a: 0.32 ± 0.36
G1b: 0.57 ± 0.54
G1c: 0.46 ± 0.47
G1/BL: P =
0.0001
Subscale V:
G1a: -0.11 ± 0.45
G1b: -0.42 ± 0.23
G1c: -0.09 ± 0.46
G1/BL: P = NS
VABS
Maladaptive
Behavior
subscales score,
12 weeks, mean
± SD:
G1a: 13.8 ± 6.0
G1b: 20.2 ± 8.2
G1c: 19.5 ± 9.1
G1/BL: P = 0.000
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
McDougle et al.,
1998 (continued)
Harms:
Withdrew due to
persistent agita-
tion despite
chloral hydrate: 3
Adverse effects,
completers, n:
Anorexia:
G1: 1
Headache:
G1: 1
Tinnitus:
G1: 1
Alopecia:
G1: 1
Weight gain:
G1: 3
Sedation:
G1: 1
Anxiety/agitation:
G1: 2
Comments:
* Chloral hydrate 500 to 1000 mg could be administered to any patient up to four times in 24 hours for agitation, as
needed. No other psychotropic drugs were administered to the patients during the study.
CGI was assigned by the research nurse with input from the patient (when possible) and the patient’s treatment team.
No adverse cardiovascular, extrapyramidal, or proconvulsant effects were identified.
Statistical analyses: ANOVA of time effects; ANOVA by ASD subtype also available in Table 1 for all scales and
subscales
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Brodkin et al.,
1997
Country:
US
Enrollment
period:
NR
Funding:
National Alliance
for Research on
Schizophrenia and
Depression,
Connecticut
Department of
Mental Health and
Addiction
Services, NIH,
CoCensys
Pharmaceuticals
Author industry
relationship
disclosures:
NR
Design:
Case series (open
label)
Intervention:
Open label treatment with
Clomipramine. Initial dose
50 mg daily, increased by
50 mg every 3 or 4 days
to a maximum dosage of
250 mg daily, as
tolerated, if maximal
clinical response was not
obtained. The maximum
dosage of clomipramine
was attained within 3
weeks, and patients
received this dose for a
minimum of 9 weeks.
Average daily dose (mg):
139.4 ± 50.4
Intervention target:
Total repetitive thoughts
and behavior, aggression,
aspects of social
relatedness, such as eye
contact and verbal
responsiveness, change
in these specific symptom
clusters over time, autistic
behavior, full-scale IQ,
CGI, and adverse effects
Primary outcome:
CGI
Groups:
G1: clomipramine
Ga: responders (CGI
scores of 1 = "very much
improved" or 2 = "much
improved" at the end of
week 12)
Gb: nonresponders
Treatment duration:
12 weeks
Frequency of contact
during study:
Every 4 weeks
Last followup post-
treatment:
End of 12 weeks
Measure of treatment
fidelity/adherence
reported:
Yes
Inclusion criteria:
• Principal diagnosis of
PDD
• Did not meet criteria for
any other DSM-IV Axis I
or Axis II disorder other
than mental retardation
Exclusion criteria:
• DSM-IV criteria for a
psychotic disorder
• Abused illicit substances
within the previous 6
months
• Serum pregnancy test
positive (females)
• Significant acute medical
condition
Age, yrs, mean ± SD:
G1: 30.2 ± 7.0 (n=35)
G1a: 30.7 ± 7.0
G1b: 29.6 ± 6.4
Mental age:
NR
Gender, n :
Male:
G1: 24
Female:
G1: 11
DSM-based diagnostic
approach reported:
Yes (DSM-IV, ADI, ADOS)
IQ (full scale),
mean ± SD:
G1: 64.6 ± 27.2
G1a: 62.7 ± 28.4
G1b: 67.0 ± 26.5
G1a/G1b: P = NS**
ABC score, mean ±
SD:
G1: 101.4 ± 17.5
G1a: 107.3 ± 17.2
G1b: 94.2 ± 15.4
G1a/G1b: P = NS**
Y-BOCS score,
mean ± SD:
Total:
G1a: 18.7 ± 6.8
G1b: 17.9 ± 6.2
Obsession
subscale, verbal
patients (n=18):
G1a: 10 ± 6.8
G1b: 6.7 ± 6.2
Compulsion
subscale:
G1a: 13.7 ± 3.3
G1b: 13.9 ± 2.5
Brown Aggression
scale total score
score, mean ± SD:
G1a: 10.6 ± 7.4
G1b: 6.5 ± 4.1
Ritvo-Freeman
Real-life rating
overall score,
mean ± SD:
G1a: 0.72 ± 0.54
G1b: 0.45 ± 0.43
CGI score, mean
± SD:
G1a: 1.89 ± 0.32
G1b: 3.8 ± 0.86
G1/BL: P < 0.001
G1a/G1b: P <
0.001
Y-BOCS score,
mean ± SD:
Total:
G1a: 9.1 ± 3
G1b: 17.3 ± 7.8
G1/BL: P < 0.001
G1a/G1b: P <
0.001
Obsession
subscale, verbal
patients (n=18):
G1a: 4.4 ± 2.8
G1b: 8 ± 6.6
G1/BL: P = NS
G1a/G1b: P <
0.001
Compulsion
subscale:
G1a: 6.9 ± 2.1
G1b: 12.5 ± 3.3
G1/BL: P < 0.001
G1a/G1b: P <
0.001
Brown
Aggression
scale total score
score, mean ±
SD:
G1a: 3.7 ± 3.6
G1b: 6.4 ± 4.6
G1/BL: P < 0.001
G1a/G1b: P <
0.001
Ritvo-Freeman
Real-life rating
overall score,
mean ± SD:
G1a: 0.18 ± 0.24
G1b: 0.44 ± 0.40
G1/BL: P < 0.001
G1a/G1b: P <
0.001
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Brodkin et al.,
1997 (continued)
Co-interventions held
stable during treatment:
Yes
Concomitant therapies,
n:*
Carbamazepine (800mg):
G1: 2
Phenobarbitol:
G1: 1
N at enrollment:
G1: 35
N at followup:
G1: 33
G1a: 18
G1b: 15
Harms, n:
Clinically
significant side
effects:
G1: 13/33
Dropped out due
to AE (agitation
and cramping,
respectively):
G1: 2
Weight gain:
G1a: 3
G1b: 0
Constipation:
G1a: 2
G1b: 1
Seizure:***
G1a: 1
G1b: 2
Sedation:
G1a: 1
G1b: 1
Agitation:
G1a: 0
G1b: 1
Anorgasmia:
G1a: 1
G1b: 0
Comments:
* Chloral hydrate (500-1000 mg) could be administered up to 4 times a day for agitation, as needed.
** No significant relationship between treatment response (G1a vs. G1b) as defined by either ABC score (<78 vs.
=78) or IQ (=70 vs. >70)
*** Two patients had a prior history of seizures.
Results by disease diagnosis type not included here, as there were no significant differences among diagnostic
subtypes in the change any outcomes over the course of treatment.
No significant difference in clomipramine dosage between G1a (131 ± 53 mg daily) and G1b (150 ± 47 mg daily).
Significant improvement over time was identified for each subscale of the Ritvo-Freeman Real-Life Rating Scale
(n=33), including Sensory Motor Behaviors (P < 0.001), Social Relationship to People (P < 0.001), Affectual
Reactions (P < 0.01), Sensory Responses (P < 0.001), and Language (P < 0.02).
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Bebko et al., 1996
Country:
Canada
Enrollment
period:
1993
Funding:
Sharp Canada
Author industry
relationship
disclosures:
NR
Design:
Prospective case
series
Intervention:
Facilitated communication
(FC) using multiple
methods for 6 weeks with
up to 7 months of follow
up data
Intervention target:
Communication
Primary outcome:
Percentage of correct
responses on three
designs: setwork (visual
stimulus with picture
cards and words),
headphones (audio
stimulus with separate
audio channels for
student and facilitator),
and receptive vocabulary
(tasks from PPVT-R). The
experimental conditions
for the setwork design
were combinations of
intervention with FC vs.
no FC and facilitators that
were informed vs. not
informed. The
experimental conditions
for the headphones
design were the facilitator
receiving the same word
as the student, a different
word, or a neutral word.
Groups:
G1: All participants all
receiving facilitated
communication
G2: All participants none
receiving facilitated
communication
Ga: facilitator informed
Gb: facilitator not
informed
Treatment duration:
6 weeks; follow up 5 to 7
months (with additional
FC use)
Frequency of contact
during study:
NR
Inclusion criteria:
• From one of four class-
rooms of a regional
program specializing in
autism
• Consent obtained
Exclusion criteria:
• See inclusion criteria
Age, yrs, mean (range):
G1&G2: 13 (6-21)
Mental age, range:
G1: 1 year 3 months to
4 years 0 months
Gender, n (%):
Male:
G1&G2: 15 (75)
Female:
G1&G2: 5 (25)
DSM-based diagnostic
approach reported:
Yes
Setwork design, %
correct responses:
G1a: 56.86
G1b: 30.00
G2a: 36.71
G2b: 35.71
G1a/G1b/G2a/G2b:
P = 0.0138
Headphones
design, % correct
reponses:*
G1a: NR
G1b: NR
G2a: NR
G2b: NR
G1a/G1b/G2a/G2b:
P = NS
Receptive
vocabulary design,
% correct
responses:*
G1a: NR
G1b: NR
G2a: NR
G2b: NR
G1a/G1b/G2a/G2b:
P = NS
Setwork design,
follow up, %
correct
responses:
G1a: 75.00
G1b: 25.57
G2a: 53.57
G2b: 32.57
G1a/BL: P =
0.345
Ga/Gb: P < 0.01
Ga/BL: P < 0.03
Headphones
design, %
correct
reponses:
G1a: NR
G1b: NR
G2a: NR
G2b: NR
G1/BL: P > 0.30
Harms:
NR
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Bebko et al., 1996
(continued)
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1&G2: 20
N at 5-7 month followup:
G1&G2: 7
Comments:
* Data reported graphically
Baseline results taken over initial 6 weeks
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
McDougle et al.,
1996
Country:
US
Enrollment
period:
NR
Funding:
NIH, Connecticut
Dept. of Mental
Health and
Addiction
Services, Korczak
Foundation for
Autism and
Related Disorders
Author industry
relationship
disclosures:
NR
Design:
Double-blind,
placebo-controlled
randomized
crossover trial
Intervention:
Acute tryptophan
depletion. 24 hours of a
low tryptophan diet
followed by tryptophan-
free amino acid drink or
sham (amino acid drink
with tryptophan added).
Behavior measurements
were taken at baseline,
180, 300, and 420
minutes after the amino
acid drink. Patients
resumed normal diet until
crossover experiment
occurred 7 days later.
Intervention target:
Autistic behaviors
Primary outcome:
Biochemical measures
(plasma free and total
tryptophan) and
behavioral measures
including change in global
severity, symptoms of
autism (RFRLRS),
repetitive thoughts and re
behaviors, and 18 other
behavioral parameters
scored by VAS.
Groups:
G1: acute tryptophan
depletion
G2: sham
Treatment duration:
2 days; 7 days between
treatment and sham
Frequency of contact
during study:
1 week
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
NR
Co-interventions held
stable during treatment:
NR
Inclusion criteria:
• Adults with autistic
disorder
• No psychotropic drugs
for at least 5 weeks
Exclusion criteria:
• Identifiable cause of
autism
• Seizures
• Positive pregnancy test
Age, yrs, mean ± SD
(range):
G1+G2: 30.5 ± 8.5 (20-53)
Mental age (WAIS-R IQ)
mean ± SD:
G1+G2: 90.8 ± 23.5
Gender, n (%):
Male:
G1+G2: 16 (80)
Female:
G1+G2: 4 (20)
DSM-based diagnostic
approach reported:
Yes
Plasma
tryptophan,
micromol/L, mean
± SD:
Free:
G1: 16.0 ± 2.1
G2: 18.2 ± 10.7
Total:
G1: 105.1 ± 43.7
G2: 115 ± 29.9
RFRLRS subscale
1-5 scores:
G1: NR
G2: NR
G1/G2: P = NS
Repetitive
thoughts severity
scale score:
G1: NR
G2: NR
G1/G2: P = NS
Repetitive
behaviors severity
scale score:
G1: NR
G2: NR
G1/G2: P = NS
Behavioral VAS
scores:
G1: NR
G2: NR
G1/G2: P = NS
Plasma
tryptophan,
micromol/L,
mean ± SD:
Free:
G1: 5.0 ± 4.4
G2: 33.6 ± 7.0
G1/BL: P < 0.001
G2/BL: P < 0.003
Total:
G1: 14.7 ± 4.5
G2: 199.0 ± 53.5
G1/BL: P < 0.001
G2/BL: P < 0.001
Significant
global
worsening of
behavior
symptoms, n
(%):
G1: 11/17 (65)
G2: 0/17 (0)
G1/G2: P = 0.001
RFRLRS sensory
motor behaviors
subscale
score:**
G1: NR
G2: NR
G1/G2: P < 0.05
RFRLRS
subscale 2-5
scores:
G1: NR
G2: NR
G1/G2: P = NS
Repetitive
thoughts
severity scale
score:**
G1: NR
G2: NR
G1/G2: P = NS
Repetitive
behaviors
severity scale
score:**
G1: NR
G2: NR
G1/G2: P = NS
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
McDougle et al.,
1996 (continued)
Concomitant therapies:
NR*
N at enrollment:
G1=G2: 20
N at followup:
G1=G2: 17
Behavioral VAS
scores:
Calm:
G1: NR
G2: NR
G1/G2: P < 0.01
Happy:
G1: NR
G2: NR
G1/G2: P < 0.03
Other behaviors:
G1: NR
G2: NR
G1/G2: P = NS
Harms:
Nausea and
vomiting:
G1: 1
G2: 2
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
McDougle et al.,
1996
Country:
US
Enrollment
period:
September 1990
to December 1993
Funding:
NIH, Connecticut
Dept. of Mental
Health and
Addiction
Services, Korczak
Foundation for
Autism and
Related Disorders,
Solvay
Pharmaceuticals
Author industry
relationship
disclosures:
NR
Design:
Double-blind
placebo-controlled
RCT
Intervention:
Fluvoxamine maleate,
12 weeks, started at 50
mg daily and titrated up
by 50 mg every 3-4 days
to a maximum of 300
mg/day, in the inpatient
and outpatient settings.
Intervention target:
Symptoms of autism
Primary outcome:
Repetitive thoughts and
behaviors (Y-BOCS),
maladaptive behavior
(VMBS), aggression
(BAS), global improve-
ment (CGI), symptoms
of autism (RFRLRS)
Groups:
G1: fluvoxamine
G2: placebo
Treatment duration:
12 weeks
Frequency of contact
during study:
4 weeks
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR*
N at enrollment:
G1: 15
G2: 15
N at followup:
G1: 15
G2: 15
Inclusion criteria:
• Adults with autistic
disorder
• No psychotropic drugs
for at least 6 weeks
Exclusion criteria:
• Met criteria for
schizophrenia or had
psychotic symptoms
• Substance abuse in the
last 6 months
• Notable medical illness
including seizures
• Pregnancy test positive
Age, yrs, mean ± SD:
G1: 30.1 ± 7.1
G2: 30.1 ± 8.4
Mental age (IQ), mean ±
SD:
G1: 82.5 ± 26.8
G2: 77.3 ± 33.1
Gender, n:
Male:
G1: 13
G2: 14
Female:
G1: 2
G2: 1
DSM-based diagnostic
approach reported:
Yes
Y-BOCS score,
mean ± SD:
G1: 21.4 ± 7.3
G2: 21.5 ± 6.8
VMBS score, mean
± SD:
G1: 19.5 ± 6.8
G2: 22.3 ± 8.1
BAS score, mean ±
SD:
G1: 9.3 ± 10.8
G2: 12.3 ± 12.3
CGI score:**
G1+G2: moderate
severity
RFRLRS overall
score, mean ± SD:
G1: NR
G2: NR
Y-BOCS score,
12 weeks, mean
± SD:
G1: 13.7 ± 9.1
G2: 21.9 ± 6.7
G1/BL: P < 0.003
G2/BL: P = NS
G1/G2: P < 0.001
VMBS score, 12
weeks, mean ±
SD:
G1: NR
G2: NR
G1/G2: P < 0.001
BAS score, 12
weeks, mean ±
SD:**
G1: NR
G2: NR
G1/G2: P < 0.001
CGI score, 12
weeks, mean ±
SD:**
G1: NR
G2: NR
G1/G2: P < 0.001
Responders, CGI
much improved
or very much
improved, n (%):
G1: 8/15 (53)
G2: 0/15 (0)
G1/G2: P = 0.001
RFRLRS overall
score, mean ±
SD:**
G1: NR
G2: NR
G1/G2: P < 0.03
Harms:
Mild sedation:
G1: 2
G2: 1
Nausea:
G1: 3
G2: 1
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Willemsen-
Swinkels et al.,
1995
Country:
Netherlands
Enrollment
period:
NR
Funding:
Janusz Korczak
Foundation,
DuPont Pharma
Author industry
relationship
disclosures:
NR
Design:
Placebo controlled
crossover study
Intervention:
2 week single blind
placebo period; 3rd week,
1 dose of naltrexone-
hydrochloride (100 mg) or
placebo followed by 6
days placebo;* 4 weeks
naltrexone or placebo;
4 week wash out; then
crossover to alternate
treatment
1 dose 100 mg (1.61 ±
0.24 mg/kg), then:
1st cohort: 50 mg daily
(0.80 ± 0.13 mg/kg)
2nd cohort: 150 mg daily
(2.45 ± 0.33 mg/kg)
Intervention target:
Self-injurious behavior
Primary outcome:
Self-injurious behavior
Groups:
G1: 1st cohort, 50 mg
naltrexone hydrochloride
G2: 2nd cohort, 150 mg
naltrexone hydrochloride
G3: 1st cohort, placebo
G4: 2nd cohort, placebo
Ga: autism
Treatment duration:
4 weeks
Frequency of contact
during study:
Daily
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
Yes
Concomitant therapies,
n:
Antiepileptics: 5;
Neuroleptics: 11
Inclusion criteria:
• Two clinicians agreed
that the subject had
fulfilled the set of DSM-
III-R criteria for autistic
disorder as a child and
still fulfilled when current
behavior was considered
• Social impairment had to
be more serious than
could be expected on
the basis of the level of
mental retardation only
Exclusion criteria:
• See inclusion criteria
Age, yrs, mean ± SD:
Total: 29 ± 6.0
Mental age:
NR
Gender, n (%):
Male:
Total: 27
Female:
Total: 6
DSM-based diagnostic
approach reported:
Yes
Diagnosis, n:
ASD: 24
SIB: 26
Down syndrome: 1
Hunter’s syndrome: 1
Congenital anomalies of
unknown origin: 6
Congenital hydrocephalus:
1
ABC stereotypy
factor, mean ± SD:
G1a+G2a: 9.7 ± 4.7
G3a+G4a: 8.3 ± 5.2
ABC stereotypy
factor, mean ±
SD:
2 weeks:
G1a+G2a: 10.2 ±
4.6
G3a+G4a: 8.8 ±
5.0
4 weeks:
G1a+G2a: 10.0 ±
4.7
G3a+G4a: 9.0 ±
4.8
G1+G2/G3+G4: P
= 0.018
G1+G3/G2+G4: P
= NS
CGIS rating
score, mean ±
SD:
4 weeks:
G1: NR**
G2: NR**
G3: NR**
G4: NR**
G1+G2/G3+G4: P
= 0.03
G1+G3/G2+G4: P
= NS
Harms, n:
Withdrew due to
adverse effect:
G1: 1
G2: 0
Sedation:
G1: 0
G2: 3
Increase in SIB
and acting out
behavior:
G1: 1
G2: 0
Nausea and
tiredness:
G1: 1
G2: 0
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Willemsen-
Swinkels et al.,
1995 (continued)
N at enrollment:
G1=G3: 19
G2=G4: 14
G1a: 13
G2a: 11
N at followup:
G1=G3: 18
G2=G4: 14
G1a: 12
G2a: 11
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria / Population
Baseline
Measures
Outcomes
Author:
Eberlin et al., 1993
Country:
US
Enrollment
period:
NR
Funding:
NR
Author industry
relationship
disclosures:
NR
Design:
Prospective case
series
Intervention:
Facilitated communication
Intervention target:
Communication
Primary outcome:
Number of correct
answers with screened
facilitation (the facilitator
is blind to what the
subject sees). Questions
were vocabulary
(Stanford-Binet: Fourth
Edition) and knowledge
of personal information
(Personal Interview
Questionnaire).
Groups:
G1: facilitated
communication
Treatment duration:
20 hours total (40 half-
hour sessions, 1-2
sessions per day, 3-5
days/week)
Frequency of contact
during study:
3-5 days/week over
course of study
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1: 21
N at followup:
G1: 21
Inclusion criteria:
• Diagnosis of autism
• Subjective impression by
a speech therapist that
FC may be successful
• No history of property
destruction
• Available to participate
Exclusion criteria:
• See inclusion criteria
Age, yrs, mean (range):
G1: 15.5 (11.3-20.2)
Mental age, years, range:
Social-communicative
skills:
G1: 0.3-3.2
Adaptive skills composite
score:
G1: 1.5-5.8
Receptive language:
G1: 1.4-5.3
Expressive language:
G1: 0.7-6.3
Verbal language
development scale:
G1: 1.6-5.1
Mild to moderate mental
retardation:
G1: 2
Moderate to severe mental
retardation
G1: 11
Severe to profound mental
retardation:
G1: 8
Gender, n (%):
Male:
G1: 20 (95)
Female:
G1: 1 (5)
DSM-based diagnostic
approach reported:
Yes
Stanford-Binet
vocabulary, no
facilitation, correct
answers, median
(range):
G1: 7 (0-14)
Stanford-Binet
vocabulary, initial
screened
facilitation, correct
answers, median
(range):
G1: 0 (0-14)
Personal interview,
no facilitation,
correct answers,
median (range):
G1: 1 (0-13)
Personal interview,
initial screened
facilitation, correct
answers, median
(range):
G1: 0 (0-2)
Combined score,
no facilitation,
correct answers,
median:
G1: 8
Combined score,
no facilitation,
correct answers:
0:
G1: 5
1:
G1: 2
2 or more:
G1: 14
Combined Score,
initial screened
facilitation, correct
answers, median:
G1: 0
Combined score,
no facilitation,
correct answers:
0:
G1: 19
1:
G1: 0
2 or more:
G1: 2
Stanford-Binet
vocabulary,
screened
facilitation,
correct answers,
median (range):
G1: 0 (0-14)
Stanford-Binet
vocabulary,
unscreened
facilitation,
correct answers,
median (range):
G1: NR
Personal
Interview,
screened
facilitation,
correct answers,
median (range):
G1: 0 (0-10)
Personal
Interview,
unscreened
facilitation,
correct answers,
median (range):
G1: NR
Combined
Score, screened
facilitation,
correct answers,
median:
G1: 0
Combined score,
screened
facilitation,
correct answers:
0:
G1: 15
1:
G1: 4
2 or more:
G1: 2
Answered more
questions
correctly with
screened FC
than with pre-FC
communication
skills:
G1: 1
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Eberlin et al., 1993
(continued)
Answered more
questions
correctly with
screened FC than
with pre-FC
communication
skills:
G1: 0
Combined
Score,
unscreened
facilitation,
correct answers,
median:
G1: 1
Combined score,
screened
facilitation,
correct answers:
0:
G1: 10
1:
G1: 9
2 or more:
G1: 2
Answered more
questions
correctly with
unscreened FC
than with pre-FC
communication
skills:
G1: 2
Harms:
NR
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Cook et al., 1992
Country:
US
Enrollment
period:
1988 to 1990
Funding:
Harris Center for
Developmental
Studies, NIH,
Adolescent Mental
Health Academic
Award, Autism
Society of America
in Indiana and
Illinois
Author industry
relationship
disclosures:
NR
Design:
Retrospective
case series
Intervention:
Fluoxetine administered
to treat perseverative
behavior; dose range:
20 mg every other day -
80 mg daily
Intervention target:
Improvement of Clinical
Global Impression ratings
Primary outcome:
CGI
Groups:
G1: fluoxetine
Treatment duration:
Actual days taking drug:
mean days ± SD (range):
189 ± 153 (11-426)
Frequency of contact
during study:
Monthly clinic visit
Last followup post-
treatment:
Immediately post-
treatment
Measure of treatment
fidelity/adherence
reported:
No
Co-interventions held
stable during treatment:
NR
Concomitant therapies,
n (%):
Neuroleptics:
G1: 8 (35)
Carbamazepine:
G1: 1 (4)
Lithium carbonate:
G1: 2 (9)
Clonidine and alprazolam:
G1: 1 (4)
Methylphenidate:
G1: 1 (4)
N at enrollment:
G1: 23
N at followup:
G1: 23
Inclusion criteria:
ASD
Clinician assessment and
diagnosis of
perseverative behavior
ranging from self-
injurious behavior to
complex rituals
Exclusion criteria:
See inclusion criteria
Age, yrs, mean ± SD:
G1: 15.9 ± 6.2
Mental age:
NR
Gender, n (%):
Male:
G1: 18 (78)
Female:
G1: 5 (22)
DSM-based diagnostic
approach reported:
Yes
CGI, overall
clinical severity,
mean ± SD:
G1: 5.7 ± 0.8
CGI, severity of
perseverative or
compulsive
behavior, mean ±
SD:
G1: 5.5 ± 1.5
CGI, overall
clinical severity,
mean ± SD:
G1: 4.9 ± 1.1
G1/BL: P < 0.002
CGI, overall
clinical severity,
improvement, n:
G1: 15/23
CGI, severity of
perseverative or
compulsive
behavior, mean ±
SD:
G1: 4.7 ± 1.6
G1/BL: P < 0.005
Harms, n (%):
Hyperactivity/
restlessness/
agitation:
G1: 5 (22)
Insomnia:
G1: 4 (17)
Elated affect:
G1: 4 (17)
Decreased
appetite:
G1: 4 (17)
Increased rate of
screaming:
G1: 2 (9)
Increased socially
inappropriate
behavior:
G1: 1 (4)
Crying spells:
G1: 1 (4)
Yawning:
G1: 1 (4)
Maculopapular
rash:
G1: 1 (4)
CGI side effects,
n (%):
None:
G1: 10 (43)
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Cook et al., 1992
(continued)
Do not
significantly
interfere with
functioning:
G1: 8 (35)
Significantly
interferes with
functioning:
G1: 4 (17)
Outweighs
therapeutic effect:
G1: 1 (4)
Comments:
Data on 16 additional patients with mental retardation available in paper.
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Elliott et al.,
1991
Country:
US
Enrollment
period:
NR
Funding:
NR
Author industry
relationship
disclosures:
NR
Design:
Nonrandomized
trial with crossover
design
Intervention:
Analog language teaching
sessions: conducted
individually in clinical
setting, three 15-minute
sessions/week
Natural language teaching
sessions: 3 participants in
different training settings
(garden, kitchen, shower
room); three 45-minute
sessions/week
Intervention target:
Language
Primary outcome:
NR
Groups:
G1: analog language
teaching phase
G2: natural language
teaching phase
Treatment duration:
1 month each phase
Frequency of contact
during study:
Weekly
Last followup post-
treatment:
8 weeks post-intervention
Measure of treatment
fidelity/adherence
reported:
Yes
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
N at enrollment:
G1: 23
G2: 23
N at followup:
G1: 23
G2: 23
Inclusion criteria:
DSM-III-R criteria for
autism; severe mental
retardation
Residential treatment
program
Exclusion criteria:
See inclusion criteria
Age, yrs, mean (range):
G1=G2: 26 (17-37)
Mental age (Slosson
Intelligence test and/or
Bayley Scales of Infant
Development), yrs, mean
(range):
G1=G2: 3.2 (1.7-5.1)
Gender, n (%):
Male:
G1=G2: 19 (83)
Female:
G1=G2: 4 (17)
DSM-based diagnostic
approach reported:
Yes
Three dimensional
objects identified,
n:
G1: NR
G2: NR
Two dimensional
representations
identified, n:
G1: NR
G2: NR
Nouns
generalized, post
training, mean:
G1: 15.7
G2: 12.8
G1/G2: P = NS
Items retrained,
8 weeks, mean
%:
G1=G2: 92.2
Harms:
NR
Comments:
The natural language teachings were longer than the analogue language teaching in recognition of a natural
advantage of group versus individual instruction.
Paper also includes analysis of possible effect modification by sequence of training, intellectual level, and
communicative modality.
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Author:
Nelson et al.,
1980
Country:
US
Enrollment
period:
NR
Funding:
Boston Univ.
Author industry
relationship
disclosures:
NR
Design:
Randomized
crossover trial,
unspecified
randomization
method
Intervention:
Four-step procedure to
teach the shoe-lacing
task in a clinical setting.
Crossover between two
treatment conditions
(color-coded shoelace/
eyelet prompt and no
prompt).
Followup experiment:
assessment of preference
for color-coded prompt
versus position cues.
Initial training phase (10
trials) followed by a color-
reversal phase (10 trials)
that required a binary
choice between color or
position cues.
Intervention target:
Acquisition of an adaptive
skill (a shoe lacing task).
Primary outcome:
NR
Groups:
G1: extra prompt first
G2: no extra prompt first
Treatment duration:
Until completion of the
task (approximately 30
trials/session, one
session/day)
Frequency of contact
during study:
NA
Last followup post-
treatment:
One followup session
post-treatment but timing
not specified
Measure of treatment
fidelity/adherence
reported:
NR
Co-interventions held
stable during treatment:
NR
Concomitant therapies:
NR
Inclusion criteria:
• Autism diagnosis
• Onset prior to 30 months
of age
• Five behavioral
disturbances
“characteristic of autism”
(disturbances of
perception,
developmental rate,
relating, speech and
language, and mobility)
• Inability to lace shoes
Exclusion criteria:
• See inclusion criteria
Age, yrs, mean ± SD:
G1: 11.5 ± 3.0
G2: 13.1 ± 4.1
Mental age, mean ± SD:
G1: 3.0 ± 4.1
G2: 3.1 ± 0.9
Gender, n:
Male:
Total: 13
Female:
Total: 7
DSM-based diagnostic
approach reported:
NR (study pre-dates DSM-
III)
Number of trials to
complete task,
initial treatment
condition, mean ±
SD:
G1: 108.7 ± 87.1
G2: 137.2 ± 110.7
G1/G2: P = NS
Number of trials
to complete task,
cross-over treat-
ment condition,
mean ± SD:
G1: 81.6 ± 80.7
G2: 15.9 ± 9.9
G1/G2: P < 0.05
ANOVA: inter-
vention order
effect (P < 0.01).
Harms:
NR
Interventions for Adolescents and Young Adults with Autism Evidence Table (continued)
Study
Description
Intervention
Inclusion/Exclusion
Criteria/Population
Baseline
Measures
Outcomes
Nelson et al.,
1980 (continued)
N at enrollment:
G1: 10
G2: 10
N at followup:
G1: 10
G2: 10
Abbreviations
ABC
Aberrant Behavior Checklist
ADI
Autism Diagnostic Interview
ADOS
Autism Diagnostic Observation Schedule
AQ
Autism Spectrum Quotient
AS
Asperger syndrome
ASD
Autism Spectrum Disorders
BAS
Brown Aggression Scale
BL
Baseline
BPVS
British Picture Vocabulary Scale
CAM
Cambridge Mindreading
CARS
Childhood Autism Rating Scale
CGI
Clinical Global Improvement
COPM
Canadian Occupational Performance Measure
DISCUS
Dyskinesia Identification System Condensed User Scale
DSM
Diagnostic and Statistical Manual of Mental Disorders
EOWVPT
Expressive One Word Picture Vocabulary Test
ERS
Environmental Rating Scale
ES
Effect size
FATCAT
Functional Assessment Tool for Cognitive Assistive Technology
FC
Facilitated communication
FQS
Friendship Quality Scale
G
Group
HFA
High functioning autism
IEP
Individualized Education Plan
IQ
Intelligence quotient
mg
milligrams
N, n
Number
NA
Not applicable
N-CBRF
Nisonger Child Behavior Rating Form
NIH
National Institutes of Health
NR
Not reported
NS
Not significant
NSEC
Neuroleptic Side Effects Checklist
PPVT-R
Peabody Picture Vocabulary Test – Revised
QPQ
quality of play questionnaire
RFRLRS
Ritvo-Freeman Real-Life Rating Scale
SD
Standard deviation
SE
Standard error
SHW
Sheltered workgroup
SIB
Self-injurious Behavior
SIB-Q
Self-injurious Behavior Questionnaire
SPW
Supported workgroup
SRS
Social Responsiveness Scale
SSRS
Social Skills Rating Scale
TASSK
Test of Adolescent Social Skills Knowledge
VABS
Vineland Adaptive Behavior Scales
VAS
Visual analog scale
VMBS
Vineland Maladaptive Behavior Subscales
Y-BOCS
Yale-Brown Obsessive Compulsive Scale
Yrs
Years
Appendix E. Quality Assessment Form
Study Design
1. Did the study employ a group design?
Group designs may include randomized controlled trials, prospective or retrospective cohorts, case-control studies.
NOTE: Assess studies that include 2 groups but which we will report on as case series as group design studies.
+ = yes
- = no
2. Were the groups randomly assigned?
+ = yes
- = no
3. Was there an appropriate comparison group?
The comparison group should accurately represent the characteristics of the intervention group in the absence of the
intervention. Specifically, factors that are likely to be associated with the intervention selected and with outcomes
observed should be evenly distributed between groups, if possible. These factors may include, for example, age, IQ,
severity, etc.
+ = yes
- = no or not reported (NR)
NA
4. If an RCT, was randomization done correctly?
+ = yes
- = no or not reported (NR)
NA for all non-RCTs
Considerations:
Was the approach to randomization described? Were random techniques like computer-generated, sequentially
numbered opaque envelope used?
Were technically nonrandom techniques, like alternate days of the week used?
Participant Ascertainment/Inclusion
1. Was a systematic diagnostic confirmation approach used within the study?
+ = yes
- = no or not reported (NR)
Considerations: Does the study indicate confirmation of an ASD diagnosis (e.g. reports diagnosis within study [not
necessary to indicate specific tool used], review of medical records to confirm diagnosis, etc.)
2. Was the sample clearly characterized (e.g., information provided to characterize participants in terms of
impairments associated with their ASD, including cognitive or language levels)?
+ = yes
- = no or not reported (NR)
Considerations:
Study must report at minimum a measure of language, cognition, or intellectual disability.
How reproducible is the study in terms of the sample participants? Do the authors provide enough information that
you could recreate the study population in a new study?
3. Were inclusion and exclusion criteria clearly stated?
+ = yes
- = no or not reported (NR)
Considerations:
Did the authors report this information?
4. Do the authors report attrition?
+ = yes
- = no
NA
Considerations:
Do they report loss to follow-up and/or drop-out?
Intervention
1. Was the intervention fully described?
+ = yes
- = no or not reported (NR)
Considerations:
Is there sufficient detail to allow replication of the intervention?
Does the study describe the dosage, formulation, timing, duration, intensity, etc. of the intervention?
2. For behavioral studies, was treatment fidelity monitored in a systematic way?
+ = yes
- = no or not reported (NR)
NA
3. Did the authors measure and report adherence to the intended treatment process?
+ = yes
- = no or not reported (NR)
NA
Considerations:
Does the study report number of hours of treatment or treatment sessions or time period receiving therapy (planned
vs. actually received)? Do they provide pill count data for pharmacologic interventions?
4. Did the authors report differences in OR hold steady all concomitant interventions?
+ = yes
- = no or not reported (NR)
Outcome Measurement
1. Did outcome measures demonstrate adequate reliability and validity (including interobserver reliability for
behavior observation coding)?
+ = yes
- = no or not reported (NR)
Considerations:
If the study used an established measure, has validity been established previously and do the authors provide a
reference?
If the study used a new measure, was validity established?
For interobserver coding, was reliability and /or validity tested?
2. Were the primary & secondary outcomes clearly specified a priori?
+ = yes
- = no or not reported (NR)
Considerations:
Was there a “called shot?”
3. Were outcome data collected from sources appropriate to the target outcome (e.g. parent report, teacher report,
direct behavior observation)?
+ = yes
- = no or not reported (NR)
Considerations:
Ex: Parent report for home-focused outcomes, teacher report for academic/school-focused, etc.
4. Were outcomes coded by individuals blinded to the intervention status of the participants?
+ = yes
- = no or not reported (NR)
Analysis
1. Was an appropriate statistical analysis used?
+ = yes
- = no
1a. For RCT’s, was there an intent-to treat analysis?
+ = yes
- = no
NA
Considerations:
Does the study report ITT analyses or last observation carried forward or note that all subjects were included in the
final analyses?
1b. Did the study correct for multiple testing?
+ = yes
- = no
NA
1c. For observational studies, were potential confounders and effect measure modifiers captured?
+ = yes
- = no
NA
1d. For observational studies, were potential confounders and effect measure modifiers handled appropriately?
+ = appropriate analysis
- = inappropriate analysis
NA
Considerations:
Confounders are variables that are associated both with the intervention and the outcome and that change the
relationship of the intervention to the outcome. These are variables that we would control for in analysis.
Effect measure modifiers are variables that we think of as stratifying, in that the relationship between the
intervention and outcome is fundamentally different in different strata of the effect modifier. Observational research
should include an assessment of potential confounders and modifiers, and if they are observed, analysis should
control for or stratify on them.
Was the candidate variable selection discussed/noted? Was the model-building approach described?
Were any variables unrelated to the studied variables that could have altered the outcome handled appropriately?
Were any variables not under study that affected the causal factors handled appropriately?
Appendix F. Excluded Studies
Reasons for exclusion
X-1 Ineligible population
X-2 Not original research
X-3 Ineligible study size
X-4 Does not address key questions/Not an intervention study
X-5 Not published in English
X-6 Does not contain extractable data
X-7 Unable to obtain full text
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Appendix G. Quality of the Literature
Table G-1. Quality of the literature
Author Year
Group Design
Random Assignment
Appropriate
Comparison Group
Correct
Randomization
Systematic
Diagnostic
Approach
Clear
Sample
Characterization
Clear
Inclusion/
Exclusion
Criteria
Attrition Reported
Intervention
Fully
Described
Treatment
Fidelity
Monitored
Adherence
Measured/
Reported
Concomitant
Interventions
Held
Steady/
Reported
Outcome Measures
Reliable and Valid
Outcome Data
Collected
From
Appropriate Sources
Outcomes
Coded
Blindly
Appropriate
Statistical Analysis
Rating
Laugeson 20111
+
-
+
-
-
+
+
-
+
+
-
-
+
+
-
+
P
Verhoven 20112
-
NA
NA
NA
+
+
+
NA
-
-
NA
-
+
+
-
+
P
Garcia-Villamisar
20103
+
+
+
-
+
+
+
-
+
-
NA
-
+
+
+
+
F
Gentry 20104
-
NA
NA
NA
-
-
+
+
+
+
+
-
+
+
-
+
P
Greher 20105
-
NA
NA
NA
-
-
+
NA
+
-
-
-
-
+
-
-
P
Valenti 20106
-
NA
NA
NA
+
+
+
NA
+
-
NA
-
+
+
-
+
P
Laugeson 20097
+
+
+
-
-
+
+
+
+
+
NA
+
+
+
-
+
P
Lawer 20098
-
NA
NA
NA
-
-
+
NA
-
-
NA
-
+
+
-
+
P
Garcia-Villamisar
20079
+
-
+
NA
+
+
+
-
-
-
NA
-
+
+
-
+
P
Jewell 200710
-
NA
NA
NA
-
-
+
-
+
NA
NA
-
+
+
-
+
P
Tse 200711
-
NA
NA
NA
-
-
+
+
+
-
NA
-
+
+
-
+
P
Golan 2006-112
+
-
+
NA
-
+
+
+
+
-
+
+
+
+
+
+
P
Golan 2006-212
+
-
+
NA
-
+
-
+
+
-
+
-
+
+
+
+
P
Hellings 200613
+
+
-
+
+
+
+
+
+
NA
-
+
+
+
+
+
P
Kaplan 200514
-
NA
NA
NA
-
-
+
-
-
-
NA
-
-
+
-
+
P
Howlin 200515
-
NA
NA
NA
+
+
+
-
+
+
NA
-
+
+
-
+
P
Author Year
Group Design
Random Assignment
Appropriate
Comparison Group
Correct
Randomization
Systematic
Diagnostic
Approach
Clear
Sample
Characterization
Clear
Inclusion/
Exclusion
Criteria
Attrition Reported
Intervention
Fully
Described
Treatment
Fidelity
Monitored
Adherence
Measured/
Reported
Concomitant
Interventions
Held
Steady/
Reported
Outcome Measures
Reliable and Valid
Outcome Data
Collected
From
Appropriate Sources
Outcomes
Coded
Blindly
Appropriate
Statistical Analysis
Rating
O’Connor 200416
+
+
+
-
+
+
+
NA
+
NA
NA
-
+
+
-
+
P
Van Bourgondien
200317
+
-
+
NA
-
+
-
-
-
-
NA
-
-
+
-
-
P
Garcia-Villamisar
200218, 19
+
-
+
NA
+
+
-
-
-
-
NA
-
+
+
-
-
P
Remington
200120
+
+
+
+
+
-
+
+
+
NA
-
+
+
+
-
+
F
Silver 200121
+
+
+
-
-
+
+
+
+
+
+
-
+
-
+
-
P
Mawhood 199922
+
-
+
NA
-
+
+
+
+
+
+
-
+
+
-
-
P
McDougle 199823
-
NA
NA
NA
+
+
+
+
+
NA
-
+
+
+
-
+
P
McDougle 199824
+
+
+
+
+
+
+
+
+
NA
-
+
+
+
+
+
F
Brodkin 199725
-
NA
NA
NA
+
+
+
+
+
NA
-
+
+
+
-
+
P
Bebko
199626
-
NA
NA
NA
+
+
-
+
+
-
NA
-
+
+
-
+
P
McDougle 199627
+
+
+
-
+
+
+
+
+
NA
-
+
+
+
+
+
F
Willemsen-
Swinkels 199528
+
+
+
-
+
-
+
+
+
NA
-
-
+
+
+
+
F
Eberlin 199329
-
NA
NA
NA
+
+
+
+
+
+
NA
-
+
+
-
-
P
Cook
199230
-
NA
NA
NA
+
+
-
+
+
NA
-
-
+
+
-
+
P
Elliott
199131
+
-
+
NA
+
+
-
-
+
+
NA
-
+
+
-
+
P
Nelson 198032
+
+
+
-
-
+
+
-
+
-
NA
-
+
+
-
+
P
F=fair; NA=not applicable; P=poor
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