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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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4. McGovern CW, Sigman M. Continuity and 
change from early childhood to adolescence 
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5. Fecteau S, Mottron L, Berthiaume C, et al. 
Developmental changes of autistic 
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6. Seltzer MM, Shattuck P, Abbeduto L, et al. 
Trajectory of development in adolescents 
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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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with autism or Asperger syndrome. Autism. 
2005 Dec;9(5):533-49. PMID: 16287704. 

9. Harmon A. Autistic and seeking a place in 
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10. Ganz ML. The lifetime distribution of the 
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11. Croen LA, Najjar DV, Ray GT, et al. A 
comparison of health care utilization and 
costs of children with and without autism 
spectrum disorders in a large group-model 
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12. Cimera RE, Cowan RJ. The costs of services 
and employment outcomes achieved by 
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13. Schall C, McDonough J. Autism spectrum 
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Vocat Rehabil. 2010 2010;32:81-8. 

14. Chou R, Aronson N, Atkins D, et al. AHRQ 
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Clin Epidemiol. 2010 May;63(5):502-12. 
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15. Warren Z, Veenstra-VanderWeele J, Stone 
W, Bruzek JL, Nahmias AS, Foss-Feig JH, 
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16. Owens DK, Lohr KN, Atkins D, et al. 
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Effective Health-Care Program. J Clin 
Epidemiol. 2010 May;63(5):513-23. PMID: 
19595577. 

17. Golan O, Baron-Cohen S. Systemizing 
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2006 Spring;18(2):591-617. PMID: 
16600069. 


18. McDougle CJ, Naylor ST, Cohen DJ, et al. 
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Nov;53(11):1001-8. PMID: 8911223. 

19. Willemsen-Swinkels SH, Buitelaar JK, 
Nijhof GJ, et al. Failure of naltrexone 
hydrochloride to reduce self-injurious and 
autistic behavior in mentally retarded adults. 
Double-blind placebo-controlled studies. 
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73. PMID: 7654128. 

20. Remington G, Sloman L, Konstantareas M, 
et al. Clomipramine versus haloperidol in 
the treatment of autistic disorder: a double-
blind, placebo-controlled, crossover study. J 
Clin Psychopharmacol. 2001 
Aug;21(4):440-4. PMID: 11476129. 

21. McDougle CJ, Holmes JP, Carlson DC, et 
al. A double-blind, placebo-controlled study 
of risperidone in adults with autistic disorder 
and other pervasive developmental 
disorders. Arch Gen Psychiatry. 1998 
Jul;55(7):633-41. PMID: 9672054. 

22. Garcia-Villamisar DA, Dattilo J. Effects of a 
leisure programme on quality of life and 
stress of individuals with ASD. J Intellect 
Disabil Res. 2010 Jul;54(7):611-9. PMID: 
20500784. 

23. Laugeson EA, Frankel F, Mogil C, et al. 
Parent-assisted social skills training to 
improve friendships in teens with autism 
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2009 Apr;39(4):596-606. PMID: 19015968. 

24. Tse J, Strulovitch J, Tagalakis V, et al. 
Social skills training for adolescents with 
Asperger syndrome and high-functioning 
autism. J Autism Dev Disord. 2007 
Nov;37(10):1960-8. PMID: 17216559. 

25. Silver M, Oakes P. Evaluation of a new 
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autism or Asperger syndrome to recognize 
and predict emotions in others. Autism. 
2001 Sep;5(3):299-316. PMID: 11708589. 

26. Valenti M, Cerbo R, Masedu F, et al. 
Intensive intervention for children and 
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study. Child Adolesc Psychiatry Ment 
Health. 2010;4(1). 

27. 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 20PMID: 21858588. 

28. 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 
23. PMID: 21698498. 

29. Elliott RO, Jr., Hall K, Soper HV. Analog 
language teaching versus natural language 
teaching: generalization and retention of 
language learning for adults with autism and 
mental retardation. J Autism Dev Disord. 
1991 Dec;21(4):433-47. PMID: 1778959. 

30. O'Connor IM, Klein PD. Exploration of 
strategies for facilitating the reading 
comprehension of high-functioning students 
with autism spectrum disorders. J Autism 
Dev Disord. 2004 Apr;34(2):115-27. PMID: 
15162931. 

31. Van Bourgondien ME, Reichle NC, 
Schopler E. Effects of a model treatment 
approach on adults with autism. J Autism 
Dev Disord. 2003 Apr;33(2):131-40. PMID: 
12757352. 

32. Gentry T, Wallace J, Kvarfordt C, et al. 
Personal digital assistants as cognitive aids 
for high school students with autism: results 
of a community-based trial. J Vocat Rehabil. 
2010;32(2):101-7. 

33. Nelson DL, Gergenti E, Hollander AC. 
Extra prompts versus no extra prompts in 
self-care training of autistic children and 
adolescents. J Autism Dev Disord. 1980 
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. Garc�a-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. Garc�a-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 
Psychopharmacol. 1997 Summer;7(2):109-
21. PMID: 9334896. 

43. Cook EH, Rowlett R, Jaselskis C, et al. 
Fluoxetine treatment of children and adults 
with autistic disorder and mental retardation. 
J Am Acad Child Adolesc Psychiatry. 1992 
Jul;31(4):739-45. PMID: 1993-02622-001. 

44. Miller AR, Zwaigenbaum L. New provincial 
initiatives for childhood disabilities: the 
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12;164(12):1704-5. PMID: 11450214. 

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method validation study of facilitated 
communication: II. Individual differences 
and subgroup results. J Autism Dev Disord. 
1996 Feb;26(1):19-42. PMID: 8819769. 

46. Eberlin M, McConnachie G, Ibel S, et al. 
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Disord. 1993 Sep;23(3):507-30. PMID: 
8226584. 

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therapy program goals and outcomes for 
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spectrum. J Music Ther. 2005 
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intervention for adolescents and young 
adults on the autism spectrum. Int J Educ 
Arts. 2010;11(9). 

49. 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. 

50. McPheeters ML, Warren Z, Sathe N, et al. A 
systematic review of medical treatments for 
children with autism spectrum disorders. 
Pediatrics. 2011 May;127(5):e1312-21. 
PMID: 21464191. 

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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. 

 

 

 

 


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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60. Greher GR, Hillier A, Dougherty M, et al. 
SoundScape: An interdisciplinary music 
intervention for adolescents and young 
adults on the autism spectrum. Int J Educ 
Arts. 2010;11(9). 

61. Laugeson EA, Frankel F, Mogil C, et al. 
Parent-assisted social skills training to 
improve friendships in teens with autism 
spectrum disorders. J Autism Dev Disord. 
2009 Apr;39(4):596-606. PMID: 19015968. 

62. Tse J, Strulovitch J, Tagalakis V, et al. 
Social skills training for adolescents with 
Asperger syndrome and high-functioning 
autism. J Autism Dev Disord. 2007 
Nov;37(10):1960-8. PMID: 17216559. 

63. Silver M, Oakes P. Evaluation of a new 
computer intervention to teach people with 
autism or Asperger syndrome to recognize 
and predict emotions in others. Autism. 
2001 Sep;5(3):299-316. PMID: 11708589. 

64. Valenti M, Cerbo R, Masedu F, et al. 
Intensive intervention for children and 
adolescents with autism in a community 
setting in Italy: A single-group longitudinal 
study. Child Adolesc Psychiatry Ment 
Health. 2010;4(1). 

65. O'Connor IM, Klein PD. Exploration of 
strategies for facilitating the reading 
comprehension of high-functioning students 
with autism spectrum disorders. J Autism 
Dev Disord. 2004 Apr;34(2):115-27. PMID: 
15162931. 

66. Elliott RO, Jr., Hall K, Soper HV. Analog 
language teaching versus natural language 
teaching: generalization and retention of 
language learning for adults with autism and 
mental retardation. J Autism Dev Disord. 
1991 Dec;21(4):433-47. PMID: 1778959. 

67. 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. 

68. 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. 

69. Brodkin ES, McDougle CJ, Naylor ST, et al. 
Clomipramine in adults with pervasive 
developmental disorders: a prospective 
open-label investigation. J Child Adolesc 
Psychopharmacol. 1997 Summer;7(2):109-
21. PMID: 9334896. 

70. Bebko JM, Perry A, Bryson S. Multiple 
method validation study of facilitated 
communication: II. Individual differences 
and subgroup results. J Autism Dev Disord. 
1996 Feb;26(1):19-42. PMID: 8819769. 

71. Cook EH, Rowlett R, Jaselskis C, et al. 
Fluoxetine treatment of children and adults 
with autistic disorder and mental retardation. 
J Am Acad Child Adolesc Psychiatry. 1992 
Jul;31(4):739-45. 

72. 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. 


73. 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. 

74. Garc�a-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. Garc�a-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, 
Cosejer�a de 
Asuntos Sociales 
de la Comunidad 
Aut�noma 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, Cosejer�a 
de Asuntos 
Sociales de la 
Comunidad 
Aut�noma 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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