Clinician's Manual On Autism Spectrum Disorder

Evdokia Anagnostou · Jessica Brian
Editors
Clinician’s Manual
on Autism
Spectrum Disorder
Clinician's Manual
On Autism
Spectrum Disorder
Editors
Evdokia Anagnostou
Jessica Brian
Clinician's Manual
On Autism
Spectrum Disorder
Editors
Evdokia Anagnostou and Jessica Brian
Autism Research Centre
Holland Bloorview Kids Rehabilitation Hospital
University of Toronto
Toronto, Ontario
Canada
ISBN 978-3-319-03055-5 ISBN 978-2-319-03056-2 (eBook)

DOI 10.1007/978-3-319-03056-2
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Contents
Contributor list vii
Acknowledgments ix
Author biographies xi
1 Introduction 1
References 3
2 Diagnosis: screening, surveillance, assessment, 5

and formulation
Assessment of autism spectrum disorder: surveillance and screening 5
Team structure and function 8
Components of diagnostic assessment 10
Formulation and feedback 13
References 16
3 Common psychiatric comorbidities and 19

their assessment
Introduction 19
Prevalence of psychiatric comorbidity in autism spectrum disorder 20
The DSM-5 and diagnosis of psychiatric comorbidity in
autism spectrum disorder 21
Assessment of psychiatric comorbidity 22
Conclusions 29
References 30
4 Medical comorbidities in autism spectrum disorder 33

Introduction 33
Epilepsy 34
Gastrointestinal conditions 35
Sleep issues 37
Associated genetic syndromes 39

v
vi • CO NTE N TS
Conclusions 40
References 40
5 Pharmacotherapy in autism spectrum disorder 43

Introduction 43
Symptom-based approach to the treatment of autism
spectrum disorder 44
Monitoring 53
Complementary and alternative medications 53
Conclusions 59
References 59
6 Behavioral and educational interventions 63

Behavioral interventions 64
Parent education and training 66
Interventions for disruptive behavioral problems 68
Social skills interventions 69
Educational interventions 70
Intervention for adults 72
References 74
7 Autism spectrum disorder and the family: examining

impacts and the need for support 77
Introduction 77
Impact of autism spectrum disorder on families 80
Navigating the transition to adulthood 81
Considerations following a diagnosis of autism spectrum disorder 82
Implications for practitioners 83
Conclusions 84
References 85
8 Future directions 87
Future advances 88
Conclusions 90
References 91
Contributors
Stephanie Ameis
Susan Bryson
Daniel Coury
Christopher Kilmer
David Nicholas
Melanie Penner
Wendy Roberts
Sharon Smile
Isabel Smith
Peter Szatmari
Jennifer Walton
Lonnie Zwaigenbaum
VII
Acknowledgments
We acknowledge the contribution of Dr Alana Iaboni at the Autism
Research Centre, Bloorview Research Institute, University of Toronto,
for her assistance with this manuscript.
Ix
Author biographies
Stephanie Ameis, MD, is the inaugural O’Brien Scholar and a clinician-
scientist within the Child and Youth Mental Health Collaborative between
the Centre for Addiction and Mental Health (CAMH), The Hospital for Sick
Children and University of Toronto, Canada. She is Assistant Professor
in the Department of Psychiatry, Faculty of Medicine at the University
of Toronto. Dr. Ameis’s clinical work focuses on providing assessment
and care to children and youth with autism spectrum disorder (ASD)
at CAMH. Her research work focuses on using advanced neuroimaging
techniques to study how variation in the structure and function of brain
circuits increases susceptibility for neuropsychiatric disorders that affect
children and adolescents, with a focus on ASD, obsessive compulsive
disorder (OCD), and disruptive behavior disorders. Dr. Ameis’ research
work also uses longitudinal brain imaging to track the effects of novel
and existing treatments on brain structure and function over time.
Evdokia Anagnostou, MD, Senior Clinician Scientist, Bloorview Research

Institute; Associate Professor, Department of Pediatrics, University of
Toronto; Tier II Canada Research Chair in translational therapeutics in
ASD. Dr. Evdokia Anagnostou is a child neurologist and a senior clini-
cian scientist at the Bloorview Research Institute at the University of
Toronto, Canada. She received her undergraduate degree from McGill
University, completed her neurology training at McGill University in
2003, and a postdoctoral fellowship in autism/developmental disabilities
at Mount Sinai School of Medicine in 2005. With a mission of improving
outcomes and quality of life for children with ASD and their families,
Dr. Anagnostou joined the Bloorview Research Institute in 2008, where
she built and co-leads the Autism Research Centre. She has extensive
funding in translational neuroscience and neuropsychopharmacology.
xI
xII • AUTHOR BIOGRAPHIES
Jessica Brian, PhD, C.Psych, is a Psychologist and Clinician-Investigator

at Holland Bloorview Kids Rehabilitation Hospital and Assistant Professor
in the Department of Pediatrics at the University of Toronto, Canada.
She received her PhD in Clinical-Developmental Psychology at York
University in Toronto. Dr. Brian currently co-leads the Autism Research
Centre at the Bloorview Research Institute with Dr. Evdokia Anagnostou.
Her primary research interests include the emergence of ASD in infancy
and toddlerhood, and the development, evaluation, and dissemination
of evidence-based early intervention. She has been involved in a range
of multi-site research programs aimed at understanding the emergence
of ASD, characterizing its behavioral phenotype, and identifying genetic
markers of ASD and related disorders. She is currently focusing on the
development and evaluation of behavioural interventions for toddlers
at risk for ASD. For over a decade, Dr. Brian has been involved in the
Canadian Infant Siblings Study, now part of the international Autism
Speaks Baby Sibs Research Consortium.
Susan Bryson, PhD, has been at Dalhousie University and the IWK since
2001 as Professor in Pediatrics and Psychology and first holder of the Craig
Chair in Autism Research. Her research focuses on the early detection
and treatment of ASD, as well as attention, emotion and temperament
in ASD. In 2005, Dr. Bryson took the lead in establishing Nova Scotia’s
innovative Early Intensive Behavioral Intervention (EIBI) program for
preschoolers with ASD. Building on the success of this program, she has
since led the development of the Social ABCs, a parent-mediated inter-
vention for toddlers with ASD. Dr. Bryson completed her PhD in Clinical
Psychology at McGill University, Canada. She has received many pres-
tigious awards, including both the Queen’s Golden and Diamond Jubilee
Medals for her contributions to autism.
Daniel Coury, MD, FAAP, is Professor of Pediatrics and Psychiatry in the

College of Medicine at The Ohio State University and chief of the Section
of Developmental and Behavioral Pediatrics at Nationwide Children’s
AUTHOR BIOGRAPHIES • xIII
Hospital in Columbus, Ohio. He conducts research and provides care for

individuals with autism. His primary focus is his role as Medical Director
for the Autism Speaks Autism Treatment Network, a network of hospi-
tals and physicians dedicated to developing a model of comprehensive
medical care for children and adolescents with autism.
Chris Kilmer, BSW, RSW, is a Research Coordinator in the Faculty

of Social Work, University of Calgary (Edmonton Division) and the
Department of Pediatrics at the University of Alberta, Canada. He
brings experience in systematic and synthesis reviews in ASD, as well
as qualitative methods analysis.
David Nicholas, PhD, RSW, Associate Professor in the Faculty of Social

Work, University of Calgary (Edmonton Division); and is cross-appointed
to the Department of Pediatrics at the University of Alberta, and the
Research Insitute, The Hospital for Sick Children in Toronto. His area
of research addresses quality of life, family support, and parenting with
a focus on autism. He is currently involved in national and international
studies addressing the impact of autism on families both at the point of
diagnosis and over the course of child and adult development.
Melanie Penner, MD, FRCPC, is a developmental pediatrician with an

interest in health service delivery for children with ASD. She completed
her Bachelor of Health Sciences at McMaster University and Medical
degree at Queen's University, Canada. She completed her residency in
pediatrics and subspecialty residency in developmental pediatrics at
the University of Toronto. Dr. Penner is currently pursuing a Master’s
degree in Health Services Research at the Institute of Health Policy in the
Management and Evaluation through the Clinician Investigator program
at the University of Toronto. Her research interest is health technology
assessment of diagnostic methods and novel service delivery models for
children with ASD.
xIV • AUTHOR BIOGRAPHIES
Wendy Roberts, MD, is a developmental pediatrician who is now a

Professor Emerita at the University of Toronto. She continues to be involved
in autism care and advocacy in the community. She is Vice-Chair for the
Clinical Expert Committee of the Ontario Ministry of Children and Youth,
she collaborates in ongoing research in the genetics of autism and early
identification and intervention, and is the Clinical Director of ISAND
(Integrated Services for Autism and Neurodevelopmental Disorders),
a Not-for-Profit Centre for Autism Care across the lifespan. Dr Roberts’
research interests have focused on autism, its genetic etiology, its earliest
signs, its developmental trajectory and diagnostic stability, associated
syndromes which have autistic features (including epilepsy), and early
developmentally appropriate intervention. She has been site Principal
Investigator for several grants while co-directing the Autism Research
Unit at the Hospital for Sick Children. In 2008, Dr Roberts successfully
established Toronto as the first Canadian site of the Autism Treatment
Network (ATN), a clinical database for autism on which numerous
research studies have been built. She is also focused on helping to build
a network of integrated services and continuum of care for individuals
with ASD and their families from all over Ontario.
Sharon Smile, MD, completed her pediatric training at the University

of The West Indies, Jamaica and a clinical fellowship in developmental
pediatrics at The University of Toronto. She completed a Masters degree
in clinical epidemiology at University of Toronto. Dr Smile is currently an
Assistant Professor in the Department of Pediatrics, faculty of Medicine
at the University of Toronto, and a developmental pediatrician at Holland
Bloorview Kids Rehabilitation Hospital. Her interests include medical
and mental health comorbidities seen among children diagnosed with
ASD and intervention therapies to address comorbidities.
Isabel Smith, PhD, ScM, holds the Joan and Jack Craig Chair in Autism
Research, and is a Professor in the Departments of Pediatrics, Psychology,
AUTHOR BIOGRAPHIES • xV
Neuroscience at Dalhousie University, based at the IWK Health Centre in

Halifax, Nova Scotia, Canada. Dr. Smith’s work as a clinical psychologist
has focused on the promotion and implementation of evidence-based
practices for early identification, diagnosis, and treatment of ASD. She
has led studies of the impact of Nova Scotia’s unique model of early
intensive behavioral intervention for preschoolers with ASD since the
program’s inception in 2005. She is currently the principal investigator
of a study comparing the cost-effectiveness of different early intervention
models; other research interests include longitudinal studies of children
and youth with ASD and treatment studies addressing behavioral dis-
orders associated with ASD, such as anxiety and insomnia. As a faculty
member of the Canadian Institutes of Health Research-funded Autism
Research Training program, she contributes to the education of the next
generation of ASD researchers.
Peter Szatmari, MD, is Chief of the Child and Youth Mental Health
Collaborative between the Centre for Addiction and Mental Health
(CAMH), the Hospital for Sick Children and the University of Toronto.
Additionally, Dr. Szatmari holds the Patsy and Jamie Anderson Chair
in Child and Youth Mental Health. Dr. Szatmari’s investigative interests
fall broadly into areas of psychiatric and genetic epidemiology, specifi-
cally: longitudinal studies of children with ASD and the factors associ-
ated with good outcomes; and the genetic etiology of autism including
studying families with rare copy number variants and studies of infant
siblings. Another area of interest is the developmental course of child
and adolescent psychopathology including depression, eating disorders,
oppositional behaviors, and anxiety disorders, with a particular area of
concern being measurement issues and sampling by family unit rather
than by individuals.
Jennifer Walton, MD, MPH, FAAP, is Assistant Professor of Pediatrics in

the College of Medicine at The Ohio State University, and an attending
xVI • AUTHOR BIOGRAPHIES
physician in the Section of Developmental and Behavioral Pediatrics at

Nationwide Children’s Hospital in Columbus, Ohio. She provides care
for individuals with ASD, ADHD, and other developmental disabilities.
Her primary focus is her role is as Medical Director for the Williams
Syndrome Clinic, medical lead of the Southeastern Ohio Interdisciplinary
Assessment Team, and coordinator of the pediatric resident and medical
student clinical training for developmental and behavioral pediatrics at
Nationwide Children's Hospital.
Lonnie Zwaigenbaum, MD, PhD, completed his pediatric training at

Queen’s University, and his clinical fellowship in developmental pediatrics
at The Hospital for Sick Children in Toronto, Canada. He completed a
research fellowship and Masters degree in health research methodology
at McMaster University. Dr. Zwaigenbaum’s research focuses on early
behavioral and biological markers and developmental trajectories in
children and youth with ASD. He currently holds an Alberta Innovates
Health Solutions Health Scholar Award and the Stollery Children’s
Hospital Foundation Chair in Autism Research. Dr. Zwaigenbaum is a
Professor in the Department of Pediatrics at the University of Alberta,
and the co-director of the Autism Research Centre based at the Glenrose
Rehabilitation Hospital.
Chapter 1
Introduction
Evdokia Anagnostou, Jessica Brian
Autism spectrum disorder (ASD) has been redefined in the most recent
Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to include
deficits in social communication and repetitive behaviors/restricted inter-
ests [1]. Language and cognitive deficits are now considered orthogonal
to the diagnosis. A series of specifiers are available to allow for better
description of each individual child and a severity matrix has been pro-
posed for the first time. However, the most significant implication of
the DSM-5 changes is that clinicians are challenged to admit that they
do not yet know how to describe the heterogeneity of the spectrum in
terms of biologically distinct groups.
There has been an explosion in genomics and systems neuroscience
relating to ASD, which has the potential to start bringing clarity to the
field. For example, at least 10% of children with ASD have copy-number
variants (CNV), which are believed to be associated with their disorder
[2]; early whole genome sequencing would suggest that up to 50% of
children have de novo and rare inherited mutations related to their
phenotype [3]. Several of these findings are already being developed into
diagnostic tests. Of particular interest, however, is that despite the very
high number of genomic variations seen in ASD and related disorders,
network analyses would suggest that such variation maps on to distinct
biological processes, including synaptic function, chromatin remodelling,
and transcription regulation, among others. Some of these pathways are
Ó Springer International Publishing Switzerland 2015 1

E. Anagnostou and J. Brian (eds.), Clinician’s Manual
on Autism Spectrum Disorder, DOI 10.1007/978-3-319-03056-2_1
2 • CL INI C I A N’S MA N UA L O N AU T IS M S P E C T RU M D IS O RD E R
informing our approach to treatment development so that, for the first

time, it seems reasonable to expect that treatments may be developed
through the translational route.
Much debate exists around the increasing prevalence of the disorder,
with recent Centers for Disease Control and Prevention (CDC) numbers
estimating that 1 in 68 children in the US has ASD [4]. Whether this
represents reclassification or whether there are environment-by-gene
interactions responsible for true new cases remains to be established, the
fact remains that higher numbers of children are accessing our health
care systems. This, in turn, requires a systems approach to developing
evidence-based guidelines for the screening, diagnosis, and treatment
of ASD across the lifespan.
In addition, the increased prevalence of the multitude of co-occurring
conditions (both psychiatric and medical) in this population increases
the burden to both mental and physical health systems. Whether such
co-occurring conditions reveal something about the biological hetero-
geneity of ASD or whether their presence may predict specific biological
phenotypes remains to be seen. However, their presence interacts with
core symptom domain deficits to significantly affect long-term outcomes
and quality of life. As such, prompt detection of such conditions and treat-
ment may be as critical to the long-term functional outcomes of people
with ASD, as is early detection and treatment of core symptom domains.
In this book, the authors, who are experts in their respective fields,
review the evidence across several domains of interest to clinicians,
including effective screening and diagnostic procedures, pharmacologi-
cal, psychological, and educational treatments, and the impact of ASD on
families. The evidence for early detection and behavioral intervention as
predictors of optimal outcomes is strong and the authors summarize such
evidence and provide concrete guidance to clinicians about best practices.
Although no medications have been approved for the treatment of core
symptom domains of ASD, there is evidence to support their judicious
use for the treatment of associated symptoms such as attention deficit
hyperactivity disorder, anxiety, and irritability/aggression, among others.
The evidence for such a practice is reviewed and recommendations are
made. In addition, particular attention is paid to the characterization
INTRODUCTION• 3
of psychiatric and medical co-occurring conditions and approaches to

their management. Lastly, we recognize that the burden of ASD-related
dysfunction is not only experienced by individuals with ASD themselves
but also by their families and caregivers. Understanding the strengths
and challenges of children, youth, and adults with ASD, as well as their
families, is critical in order to support them proactively and within an
evidence-based family-centered health care system.
The aim of this clinician’s manual is to be an essential resource for
clinicians caring for individuals with ASD. The field has made significant
gains in our understanding of ASD and the factors that predict optimal
outcomes and this book will serve to facilitate the implementation of
evidence-based screening, diagnosis, and treatment of individuals on
the autism spectrum.
References
1 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th
Edition. Washington, DC: American Psychiatric Association; 2013.
2 Devlin B, Scherer SW. Genetic architecture in autism spectrum disorder, Curr Opin Genet Dev.
2012;22:229-237.
3 Jiang YH, Yuen RKC, Jin X, et al. Detection of clinically relevant genetic variants in autism
spectrum disorder by whole-genome sequencing. Am J Hum Genet. 2013;2:249-263.
4 Centers for Disease Control and Prevention (CDC). Data and Statistics: Autism Spectrum
Disorder (ASD). CDC. www.cdc.gov/ncbddd/autism/data.html. Accessed February 4, 2015.
Chapter 2
Diagnosis: screening, surveillance,

assessment, and formulation
Melanie Penner, Lonnie Zwaigenbaum, Wendy Roberts
Key Learning Objectives

By the end of this chapter, readers will be able to:
• identify necessary team members and define team member roles
for the diagnostic assessment of autism spectrum disorder (ASD);
• recognize how the caregiver history, history from other sources,
physical examination, informal observation, and formal
observation contribute to the diagnostic assessment;
• conceptualize and integrate the assessment findings into a
formulation that addresses the diagnostic question in the context
of the child’s neurodevelopmental profile; and
• communicate the findings of the assessment effectively with
families, providing an informative summary and interpretation.
Assessment of autism spectrum disorder:

surveillance and screening
Community health care providers and other professionals involved in
supporting optimal child development (eg, early childhood educators)
play a critical role in working with parents to identify early signs of ASD.
Screening and surveillance are complementary processes aimed at iden-
tifying children who require further assessment, with an overall goal of
reducing or preventing subsequent disability through earlier initiation of

intervention [1]. Screening refers to administering and scoring a specific

instrument (eg, parent questionnaire) to identify at-risk individuals in
need of further assessment. ‘First stage’ (or universal) screening targets
all children regardless of level of concern or other risk factors; ‘second
stage’ screening is limited to children who are flagged due to identified
concerns, a positive family history, or other risk factors (eg, medical
diagnosis with a known association with ASD).
In contrast, surveillance consists of an ongoing process that includes
inquiry about parents’ concerns and observations of the child, generally
in the context of an ongoing clinical relationship (ie, by a community
physician), to obtain an overall picture of the child’s developmental health
over time [2]. In that context, decisions about referral for further evalu-
ation are made based on clinical judgment. Developmental surveillance
can include the administration of standardized tools (including screening
questionnaires), but with the aim of obtaining additional information
to help inform clinical decision-making, rather than using scoring cut-
points as a basis for referral.
There is growing evidence supporting the clinical utility of ASD screen-
ing by community health providers (ie, predictive value of a positive
screen, potential to detect children earlier than by general monitoring
of developmental concerns) [3–5]. However, most screening research
focuses on accuracy (ie, ‘correct’ classification of children with ASD,
but not children who do not have ASD, as being at-risk and in need of
further assessment based on a positive screen) rather than meaningful
end-points such as age of diagnosis, access to early intervention and
long-term outcomes [6]. As a result, there is still considerable debate as
to what should currently be considered ‘best practice’, with some authors
advocating for broad-scale implementation of universal ASD screening
as early as 18 months in accordance with current American Academy of
Pediatrics recommendations [7,8], while others continue to argue that
more evidence is needed [9,10].
There also remains uncertainty about the relative merits of a first-
or second-stage screening strategy for ASD. First-stage screening has the
potential advantage of higher sensitivity (and thus, more children with
D I AG N O S I S: S C R E E N I N G , SU R V E I L L A N C E , A S S E S S M E N T, A N D F O R M U L AT I O N • 7
ASD being correctly identified at an early age), but also tends to identify
more children who do not have ASD (ie, false positives), with potential
implications for parental stress and straining service capacity for appro-
priate follow-up assessments. Second-stage screening also presents chal-
lenges. To be effective, general developmental surveillance must correctly
identify children with ASD for further assessment; however, there is
evidence that current screening methods may miss some children who
would otherwise be flagged by ASD-specific screens [5,11].
Recent research advances help reconcile the advantages and disad-
vantages of first- versus second-stage screening by offering a combined,
integrated approach, while at the same time, further supporting the
overall utility of ASD screening. For example, the Modified-Checklist
for Autism in Toddlers (M-CHAT) is an ASD screening tool which has
been evaluated in large community samples of 16- to 30-month-olds
assessed during well child visits. By combining a 23-item parent ques-
tionnaire with a structured follow-up interview to clarify items endorsed
by parents, the M-CHAT essentially functions as a combined level 1 and
level 2 screening tool, with approximately 50–60% of screen positive
children who are referred and assessed being subsequently diagnosed
with ASD [12–14]. Recently, Robins et al [15] reported validation data
for a new version of this instrument, the ‘Modified Checklist for Autism
in Toddlers, Revised with Follow-up’ (M-CHAT-R/F). The questionnaire
was reduced to 20 items and a scoring algorithm with three risk ranges
was developed. Children in the ‘low-risk’ range (<3 items endorsed)
did not require the follow-up interview or any other additional evalua-
tion (93% of all cases). Children in the ‘medium-risk’ range (3–7 items
endorsed; 6% of all cases) required the follow-up interview to clarify
their risk for ASD; if at least 2 items remained positive, then referral for
diagnostic evaluation was indicated. Children in the ‘high-risk’ range
(8 or more items endorsed; 1% of all cases) were at sufficiently high risk
to be referred directly for diagnostic assessment without the follow-up
interview. This revised scoring and referral algorithm reduced the initial
screen positive rate (from 9.2–7.2%) and increased the overall rate of
ASD detection (67 vs. 45 per 10,000) [15].
Wetherby et al [16] have adopted a similar strategy with the

Communication and Symbolic Behavioral Scales Infant Toddler Checklist
(CSBS-ITC), recommending that children identified by this broadband
screener, designed to detect communication delays, have an additional
assessment for behavioral ‘red flags’ [17] to further determine which
children require an ASD diagnostic assessment. The ITC has been dem-
onstrated to have very high sensitivity in a community sample, detect-
ing over 90% of children with ASD by age 24 months [16], although
evaluation of the care pathway that includes the second level behavioral
assessment has not yet been reported.
As ASD screening in community settings continues to be evaluated [6]
and health policy regarding screening continues to evolve, developmental
specialists will continue to have an important role in working with their
community colleagues to encourage careful monitoring for early signs of
ASD, understanding of referral and care pathways, and working collabo-
ratively with families though the assessment process. This collaboration
extends to helping parents understand the diagnosis and to navigate the
service system so that the child and family access appropriate supports
and services in a timely way. Establishing a positive working relation-
ship with community health professionals also lays the foundation for
ongoing co-management of the child in relation to their diagnosis, and
other potential physical and emotional health issues that may arise [18].
Team structure and function

The success of a diagnostic assessment hinges on effective teamwork.
This is true whether the diagnosis is made with a multidisciplinary team
of health care providers in a tertiary care setting or a single clinician in a
community practice. Clinicians learn to appreciate that they work in concert
with the child and his or her family to gather and synthesize information
that may lead to a diagnosis but will, more importantly, foster a greater
understanding of the child’s neurodevelopmental profile. This profile
informs not only the family, but also service providers and members of
the family’s community support system.
Most jurisdictions do not mandate which professionals need to be
involved in the diagnostic assessment. Each child will present with unique
challenges, and different team members may need to be consulted with

each new case. Table 2.1 lists potential contributions by family members
and professionals.
Because of high demand for ASD assessments, constrained health
care resources and limited geographic access to tertiary care centers, an
in-person multidisciplinary team assessment may not be possible. In such
cases, clinicians may be part of a 'virtual' team, in which assessments
occurring across time and locations are incorporated into the diagnostic
formulation. While virtual teams may allow for some efficiency, they
create an additional challenge for the team leader to synthesize informa-
tion from various contexts. Technological advances can now be used to
Team member Role

Leader Coordinates elements of the assessment
Responsible for communication of assessment results
to family
Develops management and follow-up plan
Caregivers Provide bulk of history
Provide consent to contact other individuals with
knowledge of child
Siblings Source of valuable information
Provide clinicians an opportunity to observe peer
interaction
Physician Medical and developmental history (+/– standardized
interview tools)
Physical examination
Observation (formal and informal)
Coordination of further testing (biochemical, genetic,
imaging, etc)
Psychologist Developmental history (+/– standardized interview)
Observation (formal and informal)
Intelligence or developmental assessment tools
Other formal neuropsychological tests (adaptive function,
executive function, achievement, attention/hyperactivity/
impulsivity)
Speech-language pathologist Formal assessment of language and communication skills
Assessment of speech and language pragmatics
Occupational therapist Sensory profile
Motor coordination
Table 2.1 Team members and potential contributions to diagnostic assessment.

10 • CL IN I C I A N’S MA N UA L O N AU T IS M S P E C T RU M D IS O RD E R
connect team members across settings to allow valuable team discussions

to occur with all members present, which often provides richer insight
into the child’s profile.
Components of diagnostic assessment

Patient history
A thorough and accurate history provides the foundation for a diagnosis
of ASD. Because it is often the first part of the assessment, it also allows
the clinician to develop a therapeutic interaction with caregivers. This
rapport greatly influences the tone of the assessment and can improve
receptiveness to the results of the evaluation.
The clinician should begin by asking about the caregivers’ under-
standing of the reason for the referral and their goals for the assessment.
Caregivers may or may not have been told about the possibility of ASD.
To provide informed consent for the assessment, caregivers must know
that you will be evaluating for ASD. Some approaches to broach this
topic include:
“Sometimes families have specific things they want us to

look for, such as autism spectrum disorder or attention
deficit hyperactivity disorder. Is there anything you’d like us
to look for in your child?”
“We will be looking at all areas of your child’s development;

however, your doctor wrote that (child’s name) has
challenges with his/her (language/social skills/play). In these
cases, it is important that we look for any signs of an autism
spectrum disorder.”
It is also important to start the interaction by explaining the various

components of the assessment, including the amount of time and
number of appointments you anticipate. By helping caregivers under-
stand what to expect, clinicians can foster a trusting environment that
will relieve some anxiety for the family.
The clinician should then gather more information about the
caregivers’ concerns and observations that have been communicated to
them by other people in the child’s life. It is important to solicit informa-

tion about how the child functions in multiple environments, such as
daycare, school and recreational activities.
The history should explicitly cover all DSM diagnostic criteria with
clear examples of each criterion when present. The Autism Diagnostic
Interview – Revised (ADI-R) [19] is a standardized interview that can be
completed by an experienced clinician in approximately 1.5 to 2 hours and
is useful for children with a mental age of at least 2 years of age. The ADI-R
consists of 93 items grouped into domains of Language/Communication;
Reciprocal Social Interactions; and Restricted, Repetitive, and Stereotyped
Behaviors and Interests.
The developmental history should cover all developmental domains
regardless of the reason for referral. While the focus should be on current
skills, the progression of communication and social skills is essential to
elicit, as is any significant loss of previously acquired skills (regression).
Many clinicians choose to incorporate a standardized adaptive skills inter-
view, such as the Vineland Adaptive Behavior Scales II (VABS-II) [20],
to measure current performance across domains of development. The
VABS-II can be incorporated into a developmental history and provides
a standardized measure of the child’s current developmental function
with standard scores, percentiles, and age equivalents.
The history should also include a thorough past medical history, includ-
ing the pregnancy and neonatal period. The review of systems should
pay particular attention to hearing, vision, sleep, nutrition, and gastroin-
testinal symptoms. A three-generation family history should be elicited
including ASD, developmental delays, school failure, learning disabilities,
language delays, attention deficit hyperactivity disorder, anxiety (par-
ticularly social anxiety) or other psychiatric conditions, hearing impair-
ment, seizures, congenital anomalies, multiple spontaneous abortions,
and consanguinity. A social history, including living situation, employ-
ment, and support is important and may influence the management plan.
Questionnaires
In cases where a formal ASD interview tool such as the ADI-R is not
feasible, clinicians may choose to provide caregivers with questionnaires,
which are less time-consuming and can be completed between appoint-

ments. These questionnaires can also be given to other individuals who
have frequent contact with the child, such as child care staff and teachers.
The Social Communication Questionnaire (SCQ) [21] is a screening
tool based on the ADI-R that can be used for children over 4 years with
a mental age over 2 years of age. It consists of 40 'yes/no' items and can
be quickly and easily completed by caregivers. Some clinicians prefer
to use it as a guide in a semi-structured interview format to cover the
diagnostic criteria systematically during the history taking.
The Social Responsiveness Scale-2 (SRS-2) [22] is designed to identify
social impairment that is seen in ASD and to differentiate it from social
difficulties that occur in other disorders. It can be completed for children
as young as 30 months and takes approximately 15 minutes for caregiv-
ers to complete.
Informal observation
The child may not need to be present for the entire developmental history;
however, it is important to observe the child in the same room as the car-
egivers for part of the assessment. This time is filled with rich information
about the interaction between the child and caregivers, how the child
adapts to the new environment, the child’s attempts to obtain, maintain,
and direct the caregiver’s attention, and how the caregiver deals with
undesirable behavior.
Formal observation
In most cases, clinicians will use a formal observational tool to help
them systematically observe behaviors consistent with DSM criteria. The
Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) [23] is a
frequently utilized semi-structured interaction that provides structured
opportunities to assess communication, social interaction, play, and
restricted and repetitive behaviors. Clinicians must undergo training to
administer and score the ADOS. Modules 1–4 provide cut-off scores for
ASD and can be used in children as young as 31 months; the Toddler
Module provides ranges of concern (instead of cut-off scores) and can
be used in children between 12 and 30 months of age [23].
The Childhood Autism Rating Scale (CARS-2) is a brief observational

scale with 15 items that can be used in children aged 2 and older.
Physical examination
A physical examination by a physician is a necessary component of the
diagnostic assessment because of the many medical comorbidities associ-
ated with ASD (see Chapter 3). If a physician is not part of the diagnostic
team, the child’s pediatrician can perform a thorough examination after
the diagnosis is made. The physical examination should be comprehen-
sive, with particular attention to growth parameters and dysmorphic
features. A thorough neurologic examination is warranted in all children
with suspected ASD.
Because of sensory processing difficulties, children with ASD often
have difficulty with the physical examination. It is best to attempt the
exam when the child is comfortable with the environment and in a good
mood. Because the diagnosis itself does not rely on the results of the
physical examination, it may be appropriate to complete it at a later date.
Additional assessment components

Other types of assessments, as listed in Table 2.1, may be useful depend-
ing on the individual needs of the child. At a minimum, hearing and
vision development must be documented prior to a diagnosis of ASD. A
psycho-educational assessment can be performed at the time of diagnosis
or when the child reaches school age. Many children will also benefit from
speech and occupational therapy assessments, which may help to inform
the diagnosis and formulation or can be part of the management plan.
Formulation and feedback

The formulation synthesizes the results of the assessment and feedback
involves presenting diagnostic impressions. The formulation is typically a
written summary of findings from the patient assessment(s) and is what
will be consulted by family and service providers going forward after a
diagnosis. Feedback involves presenting the formulation and sharing a
diagnosis; parents have described the impact of the feedback session as
“the hour changed our lives forever.” Because of the importance of the
feedback session, it is useful for the clinician to finalize a formulation

before giving a diagnosis.
Formulation
Introducing the formulation section with a brief summary of patient
information and observations collected from parents, the referring clini-
cian, and others in the community sets the stage for making a diagnosis.
It can include relevant developmental and medical history, symptoms
that address the diagnostic criteria, and how initial concerns about ASD
developed. After gathering a patient history, results of assessments can be
briefly summarized, along with reports from teachers, childcare profes-
sionals, and other relevant individuals who have come into contact with
the patient. This information can consist of both formal and informal
observations relating to the criteria that led to a diagnostic impression.
One method of doing this is via a ‘diagnostic paragraph’ which may
help a parent or caregiver to better understand the diagnostic criteria that
appear to have been met. An explanation of the current severity, prog-
nosis, and ASD subtype (even if an unofficial one, such as an Asperger’s
disorder) may be included in the diagnostic paragraph or may warrant
a separate discussion. Similarly, the clinician should explain how ASD
may affect dimensions of development, such as language, cognition,
developmental status, and functional or adaptive skills. Other coexisting
diagnoses such as intellectual disability, language impairment, motor
speech disorders, attention deficit hyperactivity disorder, and social or
other forms of anxiety disorders need to be discussed.
An itemized management plan and list of recommendations should
accompany a diagnosis. This can include a medical follow-up and inves-
tigation, referrals to community services, access to helpful resources for
families, and strategies tailored to the child’s various environments to
promote engagement and learning. This list should be as comprehensive as
possible, as it is often referenced by families and health care professionals
throughout the patient’s life.
Feedback
A feedback session follows a similar structure to the formulation. At each
stage, the clinician should ensure the parents/caregiver understands and
agrees with clinical observations. This will help the family to appreciate
the evidence upon which a diagnosis is based and help to prevent later
disagreement or confusion.
Some clinicians find it hard to use the term ‘autism’ with parents and
caregivers; this could be made less difficult if the medical terms have
been discussed throughout the assessment process and are reiterated
during the feedback session. After presenting the evidence, clinicians
must communicate the diagnosis in a clear and unambiguous statement.
An example of a way to communicate the diagnosis is as follows:
“[Child’s name] has difficulty sharing his/her feelings with

another person. He/she has very focused interests and insists
that the world 'stays the same.' He/she also has intense
sensory interests and repetitive movements. When we see
this combination, the name we give it is autism spectrum
disorder. Based on my assessment, he/she has autism
spectrum disorder.”
Families will have varying reactions in the moments after they receive
the diagnosis. Though the ensuing silence can be uncomfortable, it is
important to let families reflect on the impact of the diagnosis. This is
the time when the family may wish to guide the remainder of the feed-
back session with the many questions they may have about their child.
Prognosis will often be the first question from parents. Explaining
the predictors of outcome, such as early identification and intervention,
intellectual level, age when language emerges, and coexistence of other
medical issues, can be helpful for parents. Unfortunately, there is still a
great deal of uncertainty in predicting the outcome of individuals with
ASD and this must also be communicated to the family. Discussion of
a management plan is vital but may be difficult during the first session
when the diagnosis is shared. The family may require a number of

sessions to discuss the modality and intensity of interventions, medical
issues, diet and nutrition, alternative and complementary therapies, and
management of difficult behaviors and emotion dysregulation.
References
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University Press; 2011:75-89.
2 Dworkin PH. British and American recommendations for developmental monitoring: the role
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for autism spectrum disorders in pediatric primary care. J Dev Behav Pediatr. 2008;29:345-350.
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autism in low-risk toddlers. Pediatrics. 2013;131:e1121-e1127.
13 Kleinman JM, Robins DL, Ventola PE, et al. The modified checklist for autism in toddlers: a
follow-up study investigating the early detection of autism spectrum disorders. J Autism Dev
Disord. 2008;38:827-839.
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2014;133:37-45.
16 Wetherby AM, Brosnan-Maddox S, Peace V, Newton L. Validation of the infant-toddler
checklist as a broadband screener for autism spectrum disorders from 9 to 24 months of age.
Autism. 2008;12:487-511.
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spectrum disorders in the second year of life. J Autism Dev Disord. 2004;34:473-493.
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evidence-based practice. CMAJ . 2014;186:509-519.
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Accessed February 4, 2015.
Chapter 3
Common psychiatric comorbidities

and their assessment
Stephanie H Ameis, Peter Szatmari

By the end of this chapter, readers will be able to identify:
• recent evidence that indicates that a majority of children and
adolescents with autism spectrum disorder (ASD) meet symptom
criteria for at least one psychiatric disorder (particularly anxiety);
• DSM-5 guidance for diagnosing comorbid ASD and a
psychiatric condition;
• limited range of validated tools available to help support
clinicians in assessing for comorbid psychiatric disorders in ASD;
• necessity of clinical judgment in combination with direct
observation, careful history taking with caregivers, and collateral
information to determine whether a comorbid psychiatric
diagnosis should be made in individuals with ASD;
• preliminary treatment studies that have demonstrated efficacy
in treating other psychiatric symptoms (eg, attention deficit
hyperactivity disorder [ADHD]) symptoms in individuals
with ASD.
Introduction
Recent studies indicate that psychiatric comorbidity is common in ASD,
that rates of problematic psychiatric symptoms are higher in ASD than

in the general population, and that comorbid psychiatric disorders can

significantly impair functioning and interfere with therapeutic and
scholastic progress [1,2]. However, the identification and appropriate
management of psychiatric comorbidity in ASD (and research in this
area) was likely hindered by diagnostic restrictions set out in the previ-
ous edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV-TR), which precluded conferring a combined diagnosis of both
ASD and certain psychiatric disorders, such as ADHD or social anxiety
disorder (social phobia) [3]. Over the last decade, studies indicating that
individuals with ASD struggle with high rates of psychiatric comorbidity
have led to important changes in diagnostic criteria in the 2013 edition
(DSM-5) that remove previous barriers to diagnosing comorbid psychiatric
disorders in this population [4]. However, there are currently few tools
to help clinicians conduct an assessment of psychiatric comorbidity in
ASD. This chapter will summarize available evidence on the prevalence
of psychiatric comorbidity in ASD, highlight relevant changes to the
DSM-5, and provide general principles that can be applied in the clini-
cal context to guide assessment and management of common comorbid
psychiatric disorders in this population.
Prevalence of psychiatric comorbidity

Within the past decade, a number of research studies have been conducted
using psychiatric assessment instruments to assess psychiatric comorbid-
ity in ASD. Studies of children and adolescents with ASD (n=109–414)
have indicated that roughly 70% of young people with ASD, recruited
from the community, meet symptom criteria for at least one psychiatric
disorder [5–7]. Strikingly, close to half of those with ASD and psychiatric
comorbidity may meet criteria for more than one comorbid psychiatric
disorder [6,7]. Rates of ADHD and anxiety disorders are consistently
found to be high in studies of psychiatric comorbidity in ASD, with results
indicating that these disorders may be present in approximately 40–50%
of affected children and adolescents [6–10]. A recent meta-analysis
including data from over 2000 children and adolescents indicated that
among the anxiety disorders, specific phobia was most common in ASD
(affecting 30%), followed by obsessive compulsive (OCD; 17%), social
CO M M O N P S YC H I AT R I C CO M O R B I D I T I E S A N D T H E I R A S S E S S M E N T • 21
anxiety (16%), generalized anxiety (15%), separation anxiety (9%), and

panic disorder (2%) [8]. While comorbid oppositional defiant disorder
(ODD), enuresis/encopresis, sleep and mood disorders are also com-
monly reported in children and adolescents with ASD, prevalence rates
for these disorders are more variable between studies [7,11]. Although
problems with tantrums and aggression may not meet criteria for a spe-
cific psychiatric disorder, it is important to note that problems in these
areas are common among children with ASD, regardless of age, ability,
or schooling [12]. A small number of studies conducted in high function-
ing adults recruited from mental health clinics (n=54–122) have pointed
to high rates of comorbid major depressive disorder in this population
(53–70%), in addition to ADHD (43%) and anxiety disorders (50%)
[13,14]. Limited data indicate that rates of psychiatric comorbidity and
intellectual disability in adults with ASD may be similar to those seen
in adults with intellectual disability without ASD [15]. Although some
evidence has indicated that comorbid psychiatric disorders may be more
common in higher functioning individuals with ASD [16], other studies
have not found a clear relationship between psychiatric comorbidity and
ASD severity, IQ, or adaptive functioning [7]. As very few studies have
examined putative risk factors for psychiatric comorbidity in individuals
with ASD, further work is needed in this area.
The DSM-5 and diagnosis of psychiatric

comorbidity in autism spectrum disorder
The DSM-5 recognizes that individuals with ASD suffer from high rates
of psychiatric comorbidity and includes significant changes to diagnostic
criteria from the previous edition of the DSM that facilitate diagnosis of
comorbid disorders in this population [4]. The previous edition (DSM-
IV-TR) did not address comorbid psychiatric disorders as part of the
diagnostic criteria for pervasive developmental disorders (PDD) (encom-
passing diagnoses of autistic disorder, Asperger’s disorder, and perva-
sive developmental disorder-not otherwise specified) [3]. Furthermore,
ADHD could not be diagnosed if symptoms occurred exclusively during
the course of PDD, and social phobia could only be diagnosed in children
with the capacity to form age-appropriate social relationships [3]. In
sharp contrast, the DSM-5 now includes a separate specifier within the
diagnostic criteria for ASD that enables clinicians to indicate whether ASD
is “associated with another neurodevelopmental, mental, or behavioral
disorder” in their patients [4]. The DSM-5 text also clearly states that
when criteria for ASD and ADHD, anxiety, depressive or other comorbid
disorders are met, both (or even multiple) diagnoses should be made,
thereby removing previous barriers to diagnosing comorbid psychiatric
disorders in this population.
Assessment of psychiatric comorbidity

Important considerations
A number of diagnostic challenges still face clinicians attempting to
diagnose psychiatric comorbidity in ASD [17]. First, most standardized
diagnostic interviews assessing psychiatric symptoms in young people have
not been validated for ASD. Further, language impairments in ASD can
lead to challenges in eliciting thoughts and feelings that are often used
to make psychiatric diagnoses. Finally, the symptoms of ASD and comor-
bid disorders (and impairment caused by these symptoms) may overlap
resulting in difficulty distinguishing between symptoms and secondary
impairment that are part of the ASD presentation versus those that are
part of the presentation for a comorbid psychiatric disorder [17], versus
impairments that are compounded by both ASD symptoms and psychiatric
comorbidity (eg, social impairment due to ASD and social anxiety disorder).
General principles of assessment

There are a number of helpful strategies that clinicians may use when
assessing for the presence of psychiatric comorbidity in ASD. First, a
comprehensive assessment of an individual with ASD should include
both direct observation of the patient and a full history from the patient,
parents/family, or other care providers around the presence of ASD/
psychiatric/medical symptoms and secondary functional impairment [18].
Based on the extant literature, and in light of DSM-5 diagnostic criteria,
clinicians providing care to individuals with ASD must carefully screen
for all commonly comorbid psychiatric symptoms (ie, ADHD symptoms,
anxiety, mood, sleep and elimination problems, and challenging behaviors)
in this population. As individuals with ASD often present with more than
one comorbid psychiatric disorder, it is important to assess for disor-
ders that tend to co-occur (eg, anxiety and depressive disorders) both
in the general population and in individuals with ASD [19]. Given the
common occurrence of challenging (including aggressive) behaviors in
ASD and the potential safety risk that self-injury and injury to others
may cause [11], clinicians must inquire about the presence of these
behaviors in their patients, and establish both triggers (eg, anxiety,
pain, sensitivity to transitions) and the function of these behaviors (eg,
escape, avoidance, attention) [20]. Evaluating antecedents, behaviors,
and consequences ('ABCs') of challenging behaviors in ASD may help
to elucidate the meaning, origin, and impact of such behaviors and
clarify whether behaviors are part of a comorbid psychiatric presentation
requiring targeted management [20] (see Chapter 6).
The use of diagnostic interviews and symptom rating scales may help
to highlight the presence of psychiatric symptoms in ASD, and direct
further questioning on history to distinguish whether symptoms have
consistently been part of the clinical presentation (ie, present since early
childhood) or if symptoms have recently emerged, or worsened and are
associated with additional impairment and may now be indicative of a
comorbid psychiatric disorder. Once psychiatric symptoms have been
identified as present in individuals with ASD, careful attention must be
paid to whether symptoms contribute significantly to impairment over
and above impairment caused by core symptoms of ASD. For identification
and characterization of episodic psychiatric disorders (such as anxiety and
mood disorders), it is important to first establish symptoms/behaviors that
are chronically present in an individual with ASD and part of the baseline
clinical presentation (ie, restricted interests, repetitive behavior, baseline
affect). These baseline symptoms/behaviors can then be distinguished
from the onset of new ones, which may represent an episodic change
in presentation representative of a comorbid psychiatric disorder. Once
new onset symptoms/behaviors are identified, their duration, relation-
ship with recent stressors (ie, a new teacher, change in environment),
and effect on functioning can be assessed.
The Schedule for the Assessment of Psychiatric Problems Associated

with Autism (and Other Developmental Disorders [SAPPA]) is one
instrument developed to assist clinicians in distinguishing between
episodes of behavioral change in ASD that may represent psychiatric
comorbidity versus behaviors that are part of the background clinical
presentation [21,22]. As some evidence indicates that children with
ASD may be particularly sensitive to environmental context, resulting in
varying presentations of psychopathology in different settings (ie, school
vs. home), particularly for mood and anxiety symptoms, clinicians must
be cautious around drawing conclusions regarding diagnosis based on a
single informant [23]. Obtaining collateral information from teachers,
therapists, or peers (in adults) is invaluable to the process of clarifying
whether comorbid psychiatric symptoms interfere significantly with
functioning across different contexts and meet criteria for diagnosis of
a comorbid disorder.
Clinical pearls for distinguishing between autism spectrum

disorder symptoms and common psychiatric symptoms
Social anxiety versus impaired social interaction/communication
in autism spectrum disorder
Social anxiety disorder is defined in the DSM-5 as a marked fear or anxiety
around social situations that involve potential exposure to scrutiny by
peers [4]. In individuals with ASD, it is necessary to look for or inquire
about specific changes in behavior/levels of physiological arousal when a
person is engaging in a social interaction, being observed, or performing
in front of others. Signs of social anxiety in individuals with ASD may
include a change in eye contact, facial expressions, and gestures from
the individual’s typical style of social interaction in familiar situations. In
comorbid social anxiety disorder, signs of physiological arousal may be
present in social situations (ie, shaking, sweating, increased heart rate,
shortness of breath) but not at baseline. Further, social situations may be
avoided by the affected individual despite a desire to meet new people.
Obsessive compulsive disorder versus repetitive

ritualistic behaviors
In the DSM-5, obsessions are defined as persistent unwanted and intrusive
thoughts, urges, or image that cause distress or anxiety and attempts are
made to ignore/suppress, or neutralize them with some other thought
or action [4]. Compulsions are defined as repetitive behaviors or mental
acts that an individual feels driven to perform:
• in response to an obsession or according to rules that must be
applied rigidly; and
• to prevent or reduce anxiety [4].
In evaluating impairment caused by repetitive behaviors in the context of
OCD, compulsions must take up a significant portion of time (>1 hour/day)
or cause significant distress/impairment in social, occupational, or other
areas of functioning in order to meet criteria for an OCD diagnosis [4].
Although higher functioning adolescents and adults with ASD may be
able to articulate the aims of repetitive behaviors, it may not be possible
in lower functioning individuals or young children with ASD. Repetitive
thoughts and behaviors are both a core feature of OCD and ASD and,
as a result, are difficult to distinguish clinically [17]. However, some
evidence suggests that the quality and content of repetitive thoughts and
behaviors in ASD differ significantly from symptoms typically found in
OCD and can be used to help distinguish between the two disorders.
These behaviors are summarized in Table 3.1 [24].
Clarifying the onset, quality, and course of repetitive behaviors in
individuals with ASD may help to indicate whether repetitive behaviors
Obsessive compulsive disorder Autism spectrum disorder

Aggression Repetitive ordering
Contamination Hoarding
Sexual content Telling or asking
Symmetry Touching
Cleaning Tapping
Checking Rubbing
Counting Self-damaging/self-mutilation
Table 3.1 Comparison of obsessive and repetitive behaviors commonly found in obsessive
compulsive disorder and autism spectrum disorder.
have always been a part of the presentation, if the quality of behaviors

have changed or new onset behaviors has emerged, or that they may be
part of a comorbid OCD presentation.
Treating comorbid anxiety disorders

Clinical trials examining the efficacy of psychopharmacological
interventions for anxiety symptoms in ASD have yet to be published.
Therefore, the use of medications, such as selective serotonin reuptake
inhibitors (SSRIs), usually indicated in typically developing populations for
anxiety symptoms [25], is currently off-label in ASD. Several randomized
controlled trials (RCTs) have examined the use of modified cognitive
behavioral therapy (CBT) for treatment of anxiety in children and ado-
lescents with high functioning ASD [26–30]. CBT programs applied to
ASD follow general principles [1,27,29,30]:
• affect recognition training;
• the use of relaxation strategies;
• cognitive restructuring;
• graded exposure;
• parent-training component to teach parents to provide support; and
• positive reinforcement and encouragement of
independence in children
Increased use of visual supports and predictability of routine in treatment
sessions, use of reward, and incorporation of children’s circumscribed
interests into concept training are often included in CBT programs
modified for use in ASD to improve participant motivation [1,27,29,30].
Published studies (n=40–70; age range=7–14 years) that have included a
parent component in CBT treatment have demonstrated an approximately
50–75% response rate in participants with comorbid social, separa-
tion, generalized anxiety disorder, and OCD over 12–16 weeks of treat-
ment, with maintenance of treatment gains demonstrated at 3- and
6-month follow-up [27,29,30].
Assessing attention deficit hyperactivity disorder

symptoms in autism spectrum disorder
As rates of comorbid ADHD are high among individuals with ASD,
and individuals with ASD have been shown to respond to stimulant
medications [31], a careful assessment for symptoms of inattention,
hyperactivity, and impulsivity is essential for treatment planning. In
ASD, individuals may be able to attend for prolonged periods of time
when engaged in preferred activities, but may struggle with inattention
overall. Therefore, it is important to consider an individual’s ability to
attend to both preferred and non-preferred tasks. As in the non-ASD
population, the use of objective rating scales [32] can be used to assess
for the presence and severity of ADHD symptoms across two settings in
individuals with ASD. If symptoms meet criteria for ADHD, a comorbid
diagnosis should be made.
Treating comorbid attention deficit hyperactivity disorder

To date, a small number of RCTs have examined the efficacy of psycho-
tropic medications for treatment of inattention, hyperactivity, and impul-
sivity in ASD [31]. Two large studies have found the atypical antipsychotic,
risperidone, to be superior to placebo for treatment of hyperactivity in
children and adolescents with ASD aged 5–17 years [33,34].
Two additional large trials demonstrated the superiority of a second
atypical antipsychotic, aripiprazole, for the treatment of hyperactivity in
children and adolescents 6–18 years of age, with ASD [35,36]. Although,
there is some evidence for the efficacy of atypical antipsychotics for
treatment of ADHD symptoms in ASD, these medications are associated
with significant adverse effects (eg, weight gain, metabolic effects) and
should only be initiated following careful consideration with families
around the costs and benefits of treatment and in the context of close
metabolic monitoring [20].
Two RCTs in children aged 5–14 years examined the efficacy of

the stimulant methylphenidate as treatment for ADHD symptoms in
ASD and reported a 50% response rate for symptoms of hyperactiv-
ity, inattention, and impulsivity [37]; however, significant adverse
effects were cause for discontinuation in 18% of those treated [38,39].
Therefore, methylphenidate treatment may be efficacious for treat-
ment of ADHD symptoms in ASD, but individuals with ASD may be less
responsive than those with a primary ADHD diagnosis and more sensi-
tive to side effects [31].
One relatively large RCT [40] and one smaller placebo crossover trial
[41] (n=16–97; age range=6–17 years; IQ>60) examined the efficacy of
atomoxetine, a norepinephrine reuptake inhibitor, for ADHD symptoms in
ASD. Both demonstrated moderate improvement in symptoms of inatten-
tion, hyperactivity, and impulsivity in treated children when compared
to placebo [40,41]. Atomoxetine was generally well tolerated with no
significant adverse effects reported [40,41].
Assessing for depressive symptoms in autism

spectrum disorder
Rates of major depressive disorder may increase with age and some
evidence suggests that prevalence may be higher in higher functioning
individuals with ASD [19]. In the DSM, major depressive disorder is defined
by a marked change from previous functioning that is accompanied by
either the presence of depressed mood or loss of interest or pleasure
(anhedonia) in all or almost all activities, with symptoms that are present
most of the day, nearly every day, for two weeks or more [4].
In order to meet criteria for major depressive disorder, depressed
mood or anhedonia must be accompanied by four additional symptoms
over the same two-week period, such as:
• change in eating/weight;
• lower energy levels;
• altered sleep patterns;
• trouble with concentration;
• psychomotor changes;
• feelings of worthlessness and guilt; and/or

• recurrent thoughts of death or suicidal ideation.
Obtaining evidence of a change in mood or levels of interest/pleasure
in activities from baseline is key to assessing for the presence of major
depression in ASD. According to a recent review of studies describing
phenomenology of depression in ASD, depressed mood has frequently been
found in individuals with ASD and comorbid depression, though it is most
often reported by a third party as opposed to the affected individual [42].
Anhedonia may manifest as a decrease in repetitive behavior or the usual
intensity of circumscribed interests. Decreased self-care may be observed
and new onset or exacerbation of maladaptive (including aggressive or
oppositional) behaviors may emerge [1]. Therefore, obtaining history
from a third party and focusing on change in observable behaviors may
help to appropriately identify depression in ASD.
Treating comorbid depression

There are currently no published studies to guide treatment of depression
in children and adolescents with ASD. A recent preliminary study of a
modified mindfulness-based therapy protocol for high functioning adults
with ASD has shown some promise for treatment of depressive symptoms
in this population; however, more research examining the efficacy
of common treatments for depression (ie, SSRIs, CBT for depressive
symptoms) in the ASD population is needed [43].
Conclusions
Psychiatric comorbidity is common in ASD and must be part of the general
assessment of affected individuals and considered when developing a
treatment plan. Recent changes in the DSM-5 now facilitate the diagnosis
of comorbid psychiatric conditions in ASD. However, there are very
few validated tools to help support clinicians in assessing for comorbid
disorders in this population. Therefore, clinicians must use psychiatric
tools with caution when assessing for psychiatric comorbidity in ASD,
and use their clinical judgment in combination with direct observation
of the affected individual, careful history taking with parents/caregivers,
family, and collateral information obtained from other relevant informants

(ie, teachers, therapists) to determine whether a comorbid psychiatric
diagnosis should be made. Currently, treatment of psychiatric condi-
tions in ASD is often based on findings regarding treatment efficacy in
non-ASD populations. Improved identification of psychiatric comorbid-
ity in ASD may help to drive assessment and treatment research in this
important clinical area.
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Chapter 4
Medical comorbidities in autism

spectrum disorder
Jennifer R Walton and Daniel L Coury

• describe commonly co-occurring medical conditions in autism
spectrum disorder (ASD);
• recognize that gastrointestinal (GI) conditions occur commonly
in ASD and can cause significant changes in behavior;
• identify genetic conditions commonly associated with ASD;
• describe evidence-based treatments for sleep problems in
individuals with ASD; and
• effectively screen for co-occurring medical conditions through
increased awareness and changes in clinicial practice.
Introduction
ASD is a behaviorally defined neurodevelopmental disorder. As the term
spectrum implies, it refers to a heterogeneous group of phenotypes with a
range of neurobiologic features. Some cases occur in other medical condi-
tions such as Fragile X syndrome; in such instances, medical comorbidi-
ties are usually seen as part of the underlying medical disorder. In ASD
that is not associated with a known medical syndrome, conditions such
as epilepsy, GI dysfunction, and sleep disorders occur more frequently
than in the general population [1]. These medical conditions occurring in

patients with a primary diagnosis of ASD may simply represent the fact
that people with ASD can also have other medical disorders. However,
others may represent part of a yet to be defined autism subtype, such
as is suggested by the association of certain mesenchymal-epithelial
transition factor (MET) gene polymorphisms with GI disorders in some
individuals with ASD [2].
Whatever the precise relationship, identification and treatment of
medical conditions in individuals with ASD is an important part of
an overall management program. This chapter will discuss the more
commonly co-occurring medical conditions and suggestions for treatment.
Epilepsy
Epilepsy has been reported to occur in approximately 7–35% of patients
with ASD [3,4]. Seizures are noted most commonly in the first 2–5 years
of life and are sometimes diagnosed concurrently with ASD. The lifetime
risk increases during adolescence, especially in patients with ASD and
intellectual disability (ID). A recent meta-analysis described a pooled
prevalence of epilepsy in 21.5% of individuals with ASD and ID, in con-
trast to 8% in those with ASD without ID [5]. These findings demonstrate
that the prevalence of epilepsy is considerably higher in individuals with
ASD and ID than in those with ASD alone, with overall rates more than
ten times that of the non-ASD population.
Epilepsy and ASD may co-occur because of common pathophysiologic
mechanisms related to abnormal synaptic plasticity and altered
excitation/inhibition ratios in the developing brain [4]. In fact, several
single gene disorders associated with both ASD and epilepsy, such as
Fragile X syndrome or tuberous sclerosis, are known to be associated
with pathways such as glutamate and γ-aminobutyric acid (GABA).
On the other hand, early seizures in the developing brain may lead to
alterations in synaptic plasticity and contribute to the development of
ASD. For example, the synapsin genes regulate neurotransmitter release
and short-term synaptic plasticity and have been associated with both
epilepsy and ASD [6]. This has led to experimental models of ASD in
genetically-modified knockout mice.
M E D I C A L CO M O R B I D I T I E S I N AU T I S M S P E C T R U M D I S O R D E R • 35
Individuals with ASD may present with variety of seizure types includ-
ing grand mal and petit mal. Partial complex seizures reportedly occur
most often, but can be difficult to assess. This is because the movements
seen in partial complex seizures can be confused with the repetitive and
unusual motor behaviors often seen as part of the behavioral presentation
of ASD. Clinicians should be alert to changes in motor behaviors and
mental status in these patients as these may be subtle signs of seizures.
Impact of epilepsy in autism spectrum disorder

Some types of epilepsy in ASD are associated with regression in social,
language, and motor skills. While this is seen most often in younger
patients (eg, epileptic encephalopathies of infancy and childhood), it
can also be seen in adolescents. The fairly abrupt onset of regression in
these individuals generally leads to lengthy evaluation, which typically
includes electroencephalography (EEG) and imaging studies, genomic
testing, and a metabolic genetics evaluation. Controversy remains around
the implications of active epileptiform EEGs in the absence of clinical
seizures. Current guidelines do not recommend routine use of screen-
ing EEGs in children with ASD [7]. However, a high degree of clinical
suspicion for epilepsy should be maintained for children with regression
in language or social communication, especially in those older than
3 years of age with language regression.
Treatment of epilepsy in autism spectrum disorder

Although the potential shared biology between epilepsy and ASD should
have implications for choice of therapeutic agents, at this point, anti-
convulsants have not been studied with respected to seizure cessation
efficacy in ASD. Thus, treatment in this population remains the same as
for individuals without autism (eg, anticonvulsants).
Gastrointestinal conditions
GI symptoms are common in the general population, although there has
been controversy over their precise prevalence in the ASD population.
Studies have shown that there are higher reports of GI symptoms in
the ASD population, as well as in other populations of individuals with

neurodevelopmental disorders, than in the general population [8]. In a
prospective study, Valicenti-McDermott et al identified GI symptoms (eg,
frequent vomiting, prior diagnosis of gastroesophageal reflux, abdominal
pain, abnormal stool pattern, characteristics of the bowel movement and
constipation) in 70% of their sample with ASD, versus 42% in a develop-
mentally disabled group, and 28% in typically developing children [8].
When identified, there has been controversy over the underlying cause
and appropriate treatment for these problems. Studies suggesting unique
autism-related pathology have been largely retracted or dismissed [9].
On the other hand, children and adolescents with ASD report common
GI conditions such as chronic constipation or diarrhea, gastroesophageal
reflux (GERD), and inflammatory bowel disease. These generally present
with the same symptoms as are seen in typically developing individuals,
although they may be harder to detect in children with limited communica-
tion abilities. However, families have reported difficulty convincing their
health care provider to conduct appropriate evaluations [10]. A thorough
review of the literature related to GI conditions in ASD has provided rec-
ommendations for treatment [11]. The strongest recommendation is for
clinicians to listen to families’ concerns and evaluate and treat GI symptoms
in individuals with ASD the same way as in typically developing children.
An important point to highlight is that, because of the core deficits in
social communication and possibly due to some sensory abnormalities,
individuals with ASD may have GI symptoms that do not manifest in
typical ways, but instead may appear as unusual behaviors. There have
been reports of individuals with writhing and aggressive behaviors
originally interpreted as being associated with underlying autism, but that
were later identified as being more similar to Sandifer syndrome [12].
This syndrome of GI disease and dystonic body movements responds
well to treatment of the underlying GI condition, rather than medical
treatment of the presenting behaviors. Clinicians should be thorough
in their history-taking and consider further investigation for possible
medical explanations for behavior changes.
More recent studies are identifying abnormalities in gut microbiota

associated with autism [13]. The full significance of these findings, and
any potential treatment for them, has yet to be determined.
Sleep issues
The importance of sleep for overall health is well known. However, studies
have shown that the prevalence of sleep difficulties in the ASD population
range from 44–86%, compared to 20–30% in the general population [14].
Kotagal and Broomall provide a detailed review of developmental aspects
of sleep dysregulation in ASD [15]. For example, a reduction in GABA
receptors in anterior and posterior cingulate gyri, which are important
in social-emotional processing, has been reported in ASD, leading to
the suggestion that there may be a relationship between reduced GABA
receptors in the cingulate cortex and the disruption of initiating and
maintaining sleep in individuals with ASD. Alteration in the release of
melatonin has also been suggested as a possible mechanism for disrupted
sleep in ASD. Sleep difficulties are not influenced by the type of ASD or
level of cognitive impairment, but there may be a correlation between
sleep difficulties and aggressive behavior, developmental regression,
and internalizing problems such as anxiety [15].
A variety of sleep disorders occur in the ASD population, with insomnia
being most commonly reported [14]. Per the American Academy of Sleep
Medicine’s diagnostic and coding manual, components of insomnia include:
• difficulty initiating or maintaining sleep;
• waking up too early and not being able to return to sleep; and
• insufficient or poor quality sleep [16].
In the ASD patient population, the cause of insomnia is multifactorial;
usually it is behavior-based, but there are other possible causes that
need to be ruled out, including neurologic, respiratory, and psychiatric
conditions [17]. These include obstructive sleep apnea, obesity, epilepsy,
anxiety, and attention-deficit hyperactivity disorder (ADHD).
The process of identifying, evaluating, and managing insomnia and
other sleep disorders in the ASD population is important and should
be thorough [15,17]. First, it is important that these individuals are
always screened, either through a questionnaire/checklist or a detailed

sleep history. Questions to pursue include the length of time it takes for
a child to fall asleep, how long the child sleeps, if there are night-time
awakenings, description of daytime naps, whether the child is taking
medications that may affect sleep or overall alertness, and if there are
daytime behaviors of concern (inattentiveness, mood swings) [15,17].
Second, the health care provider should identify any other contributors
that may relate to sleep dysfunction (including neurologic, GI, or
psychiatric conditions) and determine if they are causing the disruption
[17]. Lastly, the provider should work with the family in planning an
intervention to manage the sleep difficulties.
Interventions for sleep disorders in autism

spectrum disorder
Educational and behavioral interventions to improve sleep hygiene are
considered first-line treatment. Behavioral interventions used in typically
developing children are frequently effective, but require more attention
to parent training and support [17,18]. For those individuals with ASD
who have insomnia or delayed sleep-phase syndrome, melatonin has
been shown to be effective [19]. Supplemental melatonin has been shown
to improve sleep latency, as measured by actigraphy, in most children
at 1 or 3 mg dosages; effectiveness can be seen in week 1 of treatment
and is maintained for several months [19]. It is well tolerated, safe,
and showed additional benefits for behavior and parenting stress [19].
Melatonic has also become widely used as an initial medical treatment
in individuals without ASD.
Restless legs syndrome (RLS) is a disorder that can affect indi-
viduals with ASD and is characterized by poor sleep, frequent lower
extremity movements, and commonly, a family history of similar symp-
toms. In cases of pediatric RLS, oral iron has been found to be effec-
tive, with approximately 80% of the subjects given supplemental iron
showing improvement or resolution of their symptoms within 4 months
of beginning treatment [20].
In patients presenting with anxiety, clonidine, guanfacine, and

selective serotonin reuptake inhibitors (SSRIs) have been trialled [15].
However, currently there is limited evidence for the use of medications
to treat insomnia in children with ASD [17].
Associated genetic syndromes

Currently, the molecular basis for ASD can be identified in 10–20%
of cases [21]. Findings to date indicate that genetic contributions to
autism are highly heterogeneous. More than 200 loci have been found
to confer risk of ASD in different individuals, although each variation
accounts for less than 1% of individuals with ASD. In addition, the
phenotypic expression or penetrance of these genetic components is also
highly variable. Studies have demonstrated a range from fully penetrant
point mutations to polygenic forms with multiple gene-gene and gene-
environment interactions [22,23].
In 10% of individuals with ASD, an associated medical condition
or syndrome can be identified [24]. This includes such syndromes as:
• Fragile X;
• neurocutaneous disorders (such as tuberous sclerosis);
• phenylketonuria;
• fetal alcohol syndrome;
• Angelman syndrome;
• Rett syndrome;
• Smith-Lemli-Opitz syndrome;
• Down’s syndrome; and
• Coloboma, Heart defect, Atresia choanae, Retarded growth
and development, Genital abnormality, and Ear abnormality
(CHARGE) syndrome.
Other recently identified syndromic autisms are associated with chromo-
somal variations at 1q21, 15q13, and 16p11.2 [25]. Primary care provid-
ers who have patients with these syndromes should evaluate them for
the presence of ASD characteristics. Conversely, patients with diagnosed
ASD should undergo genetic testing to rule out other possible syndromes.
Currently, the American College of Medical Genetics recommends a

chromosomal microarray as a first-line assessment in individuals diag-
nosed with ASD, along with testing for Fragile X [26]. Specific testing for
other associated syndromes may be ordered based on level of suspicion.
In addition to associated single gene disorders, genetic testing may
be fruitful in the future to reveal associations between ASD and other
medical comorbidities. For example, the MET rs1858830 C allele, which
is important to both brain development and gastrointestinal repair has
been found to be overrepresented in families with co-occurring ASD
and GI conditions [27].
Conclusions
Individuals with ASD may present with a variety of medical conditions,
some simply co-occurring, and some likely associated with their under-
lying biology. A careful history is still the most import clinical tool, with
special attention paid to conditions which are known to be present in high
frequency, such as epilepsy, GI dysfunction, and sleep problems. Further
research into potential common biology between ASD symptoms and
medical comorbidities, as is the case for the MET polymorphism, will hope-
fully clarify the question of which conditions are simply co-occurring and
which highlight specific subgroupings within ASD. Continued education
for primary care providers for patients with ASD and other comorbidities is
critical, as these patients will need to receive comprehensive, coordinated,
and community-based care.
References
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risk based on association of MET in families with co-occurring autism and gastrointestinal
conditions. Pediatrics. 2009;123:1018-1024.
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FR, eds. Handbook of Autism and Pervasive Developmental Disorders. 2nd edn. New York, New
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of autism spectrum disorders: the case of synapsins. Front Pediatr. 2014;2:94.
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spectrum disorders: evidence based guideline. J Child Neurol. 2005;20:197-206.
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multidisciplinary diagnostic and therapeutic challenge. Eur J Pediatr Surg. 2007;17:203-206.
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Spectrum Disorders. Oxford, UK: Oxford University Press; 2011.
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and Coding Manual. 2nd edn. Westchester, IL: American Academy of Sleep Medicine; 2005.
17 Malow BA, Byars K, Johnson K, et al. A practice pathway for the identification, evaluation,
and management of insomnia in children and adolescents with autism spectrum disorders.
Pediatrics. 2012;130:S106-S124.
18 Malow BA, Adkins KW, Reynolds A, etal T. Parent-based sleep education for children with
autism spectrum disorders. J Autism Dev Disord. 2014;44:216-228.
19 Malow B, Adkins KW, McGrew SG, et al. Melatonin for sleep in children with autism:
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2012;42:1729-1737.
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22 Sebat J, Lakshmi B, Malhotra D, et al. Strong association of de novo copy number mutations
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23 Klei L, Sanders SJ, Murtha MT, et al. Common genetic variants, acting additively, are a major
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Chapter 5
Pharmacotherapy in autism
spectrum disorder
Sharon Smile, Evdokia Anagnostou

• describe the evidence for commonly prescribed medications in
autism spectrum disorder (ASD);
• identify common adverse events; and
• be familiar with monitoring recommendations.
Introduction
ASD is a complex and heterogeneous disorder which is defined by the
constellation of impairment in reciprocal social interactions, functional
communication skills, and the presence of repetitive and restricted pat-
terns of behavior and interests. Its etiology is still elusive, although a
strong genetic component has been documented and gene-environment
interactions have been hypothesized. Currently, only behavioral or psy-
chosocial treatments have evidence of benefit for core symptom domains.
Pharmacotherapy is one modality of intervention geared at removing
barriers to learning by targeting associated symptoms of ASD such as
irritability, aggression, and attention deficit hyperactive disorder (ADHD)
symptoms, among others. It is important to ensure that fundamental
interventions, such as behavioral programs that focus on skill develop-
ment, are in place prior to or concurrent with pharmacotherapy, thus
optimizing the effect of pharmacotherapy.

The limited understanding of the pathophysiology of ASD has resulted

in the absence of any pharmacological agents that have been derived
through the translational route, and as such, no pharmacotherapies have
been demonstrated to be effective for core symptom domains. Thus,
clinicians use a symptom-based approach to address maladaptive behav-
iors in ASD. This chapter will review the evidence for such an approach,
including recent randomized controlled trials (RCTs) and meta-analyses
that support this practice.
Symptom-based approach to the treatment of

autism spectrum disorder
With a symptom-based approach, clinicians look for similarities in
symptom clusters between ASD and other neuropsychiatric disorders
and essentially “borrow” established therapies that are used to treat
these other disorders and use them to address the behavioral challenges
seen in individuals with ASD. Attention difficulties, impulsivity,
hyperactivity, self-injurious behaviors, irritability, repetitive behaviors,
anxiety, obsessions, and compulsions are common behaviors exhibited
by individuals with ASD.
Hyperactivity, impulsivity, and inattention: attention

deficit hyperactivity disorder symptom cluster
The Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
diagnostic criteria for ASD now acknowledges that symptoms of hyper-
activity, impulsivity, and inattention (in isolation or in combination)
are often co-occurring in ASD, and ADHD can now be considered a
comorbid diagnosis [1]. Evidence for pharmacotherapy to treat ADHD
symptoms associated with ASD is available through clinical trials, as
well as meta-analyses, which will be discussed below. There are four
main medication categories that are currently used in the management
of an ASD/ADHD profile:
• stimulants;
• nonstimulants;
• α2-agonists; and
• antipsychotics.
P H A R M ACO T H E R A P Y I N AU T I S M S P E C T R U M D I S O R D E R • 45
Regulation of these drugs can vary by country. For example, the US Food
and Drug Administration (FDA) and Health Canada have approved the use
of stimulants (eg, methylphenidate, amphetamines), one nonstimulant,
and α2 agonists (eg, clonidine, guanfacine) for the treatment of ADHD
in children generally. Meanwhile, the UK’s National Institute for Health
and Care Excellence has approved only amphetamines, stimulants, and
nonstimulants for the management of ADHD.
Stimulants
Stimulants work centrally to enhance norepinephrine and dopamine
transmission through inhibition of dopamine/norepinephrine reuptake
in the striatum, among other less understood mechanisms. The two most
widely used groups of stimulants include methylphenidate compounds and
amphetamines. The best evidence available for stimulants comes from six
RCTs of methylphenidate involving preschool and school-aged children with
ASD [2–7]. A recent meta-analysis of four of these studies (94 participants
collectively) showed that methylphenidate is superior to placebo in treat-
ing ADHD symptoms in children with ASD (effect size [ES]=0.67; 95% CI;
0.08–1.27; P<0.05), with the strongest effect for hyperactivity in particular
(ES =0.66; 95% CI 0.03–1.03; P<0.001) [8]. There was also a trend toward
methylphenidate decreasing irritability and stereotypic behaviors, but values
did not reach statistical significance. The mean dose of methylphenidate
used in the studies ranged from 0.29–0.45 mg/kg/dose.
Most recently, Pearson et al [7] demonstrated that the combination
of long-acting and immediate-release methylphenidate was associated
with a statistically and clinically significant decrease in inattention
within the home and school environment, across multiple outcome
measures, including:
• Conners’ Parent Rating Scale-Revised (CPRS-R) inattention
subscale (P=0.001) [9];
• Swanson, Noland, and Pelham (SNAP)-IV parent-rated form
(P<0.001) [10]; and
• Conners’ Teacher Rating Scale-Revised (CTRS-R) inattention
subscale (P=0.044) [11].
This regimen was also associated with reduction in hyperactivity as

measured by parents and teachers across multiple outcome measures,
including:
• CPRS-R hyperactivity subscale (P=<0.001);
• SNAP-IV parent-rated hyperactivity subscale (P=0.001);
• ADHD Comprehensive Teacher’s Rating Scale (ACTeRS) parent
hyperactivity subscale (P<0.001);
• CTRS-R hyperactivity subscale (P<0.001) [11];
• SNAP-IV teacher hyperactive subscale (P=0.003) [10]; and
• ACTeRS teacher hyperactivity subscale (P<0.001) [7].
Adverse events of statistical significance frequently reported include
decrease in appetite, difficulty falling asleep, irritability, emotional
outbursts, and social withdrawal. The response rate of methylphenidate
in ASD is reduced compared to children who have ADHD but not ASD
(49–60% vs. 70–90%); however, the level of cognitive function does not
impact efficacy [12,13].
To date, there have been no RCTs to evaluate the efficacy of
amphetamines in children diagnosed with ASD and ADHD. Of note, an
early study that explored amphetamine use in schizophrenic children
with “autistic features” yielded minimal therapeutic effects [14]; data in
children with current or recent definitions of ASD are still pending [15].
The Autism Treatment Network has published a guideline for choosing
medications to treat ADHD-like symptoms in children with ASD [16].
Stimulants are recommended as a first-line choice of therapy in children
with the ASD/ADHD profile if not contraindicated, followed by atomox-
etine and α2-agonists as second-line, and atypical antipsychotics as a
third-line choice of therapy [16].
Nonstimulants
Atomoxetine, the only drug in its class with indications for ADHD, is a
nonstimulant which selectively inhibits norepinephrine reuptake and
has selective dopamine effects in the frontal lobe. There have been two
RCTs (one crossover, one parallel design) that support its use in the
management of ADHD symptoms in ASD [17,18]. The first, smaller study
(n=16) showed improvement of hyperactivity based on both the Aberrant

Behavior Checklist (ABC) hyperactivity subscale (P=0.04; ES=0.90) and
the DSM-IV ADHD impulsivity/hyperactivity symptoms means (P=0.005;
ES=1.27) [19]. There was also a trend towards decreased inattention
(P=0.053). In the second, larger study (n=97), atomoxetine resulted in
reduced ADHD-Rating Scale scores in the inattention subscore (P=0.003)
and hyperactivity–impulsivity subscore (P<0.001) and reduction in CTRS–
RS hyperactivity score (P=0.024) [20]. The response rate to atomoxetine
in children with ASD was less than that reported in non-ASD children
with an ADHD profile (57% vs. 63%) [17,21]. Atomoxetine use is limited
by gastrointestinal (GI) symptoms such as nausea, stomach ache, and
decreased appetite, as well as early morning awakening and tachycardia.
α2-agonists
Guanfacine functions by stimulating central α2-agonist adrenergic
receptors and has been used as a monotherapy to reduce hyperactivity
and impulsivity in children. Its efficacy in children with an ASD/ADHD
profile has been explored in one small double-blind, placebo-controlled
crossover RCT (n=11) with a 45% response rate, whilst titrating up to
3 mg/day dose [22]. Improvements were noted only in hyperactivity on
both the Parent and Teacher Aberrant Behavior Checklist (ABC) hyperac-
tivity subscales (P=0.025 and P=0.005, respectively) [19]. Comparisons
in pooled side effect severity between conditions did not meet statistical
significance; however, drowsiness, lethargy, irritability, social withdrawal,
constipation, and diarrhea were documented in the treatment group.
Clonidine, another α2-agonist, is used as an adjunctive to
methylphenidate, as well as monotherapy targeting hyperactivity and
impulsivity in ADHD. Efficacy is supported by a small double-blind placebo
controlled crossover RCT (n=8) using clonidine (0.15–0.20 mg/day in
three doses). Improvements were noted on teacher-rated ABC subscales for
irritability, stereotypy, hyperactivity, and inappropriate speech (P=0.01;
P=0.05; P=0.03; P=0.05, respectively) [23]. Teachers and parents both
identified decreased appetite and drowsiness as significant adverse
events in the treatment group.
Atypical antipsychotics
Using atypical antipsychotics to manage ADHD symptoms in ASD has
been supported by analysis of secondary measures in RCTs of risperidone
and aripiprazole targeting irritability [24–29]. Aripiprazole demonstrated
statistically significant reduction in hyperactivity as rated on the ABC
hyperactivity subscale relative to placebo controls (doses ranging from
5–15 mg/day) consistently in two RCTs [28,29]. Aman et al evaluated
the impact of risperidone on attention using the Cancellation Task and
identified no decline in the measures of attention and improvement in two
areas of cognitive processing [30,31]. Nevertheless, atypical antipsychotic
agents have a significant metabolic adverse event profile and their use
should be guided carefully by evaluation of risk-to-benefit ratio.
Summary of evidence: treatment for attention deficit

hyperactivity symptom cluster
Collectively, there is clear evidence to support the use of methylphenidate
and, to some extent, atomoxetine, α2-agonists, and atypical antipsychotics
as pharmacotherapy options for treating the ADHD symptom cluster in
the context of ASD with moderate risk of adverse events. The response
rates to these pharmacology agents are less than in non-ASD children and
youth with similar profiles, and this should be explained to parents and
youth when prescribing these medications. Further evidence is required
to guide clinicians in matching appropriate patient phenotypic profiles
to specific pharmacotherapies.
Irritability, aggression, and self-injurious behavior

symptom cluster
Irritability, aggression, and self-injurious behaviors amongst children
diagnosed with ASD are common. The etiology is variable and clinicians
should evaluate for medical comorbidities (eg, GI disturbance, sleep dif-
ficulties), psychiatric illness, emotional regulation difficulties, commu-
nication/comprehension deficits, and difficulties in understanding the
relationship between behaviors and consequences. Timely implementation
of well-designed behavioral interventions may reduce the need for psy-
choactive medications, which are commonly employed for disruptive
behavior in individuals with ASD [32]. However, the FDA has approved
risperidone and aripiprazole for children with ASD and chronic irrita-
bility/impulsive aggression. Risperidone has also been approved by the
European Medicines Agency (EMA) for this purpose.
Prior to newer antipsychotics, haloperidol was used with some success
to mitigate aggression and improve global functioning in ASD, with
evidence of a decrease in a variety of behaviors including tantrums,
hyperactivity, withdrawal and stereotypies [33,34]. Haloperidol has fallen
out of favor, however, due to the limiting factor of sedation and signifi-
cant extrapyramidal adverse events; thus, haloperidol is not generally
thought of as first-line management for maladaptive behaviors in autism.
Second generation antipsychotics have fewer and/or different, yet still
significant, adverse events and are used as first-line management. This is
supported by RCTs with aripiprazole (n=98–218 patients; aged 6–17 years)
[28,29] and risperidone (n=79–101 patients, aged 5–17 years) [24,25,35].
Most studies used the ABC irritability subscale to assess irritability [19]. A
meta-analysis showed that aripiprazole (combined n=308; 210 receiving
aripiprazole) resulted in significant reduction in scores on the irritability
(–6.17; P<0.00001), hyperactivity (–7.93; P<0.00001), and stereotypic
behavior (–2.66; P<0.00001) subscales of the ABC when compared to
placebo [36]. The response rate to aripiprazole varies from 52–56%, with a
placebo response rate ranging from 14–35%. The positive response rate (as
defined by a 25% reduction in the ABC irritability score and improvement
on the Clinical Global Impression [CGI]-Improvement scale) to risperi-
done ranges from 64–69% vs. 12–31% in the placebo group. Somnolence,
weight gain, and tremor were common adverse events reported in the
treatment group.
A meta-analysis in 2007 reviewing three RCTs showed that risperidone
leads to significant reduction in scores on the ABC irritability subscale
(mean score on treatment of 8.09 lower than control [CI –12.99–3.19]) [37].
Risperidone was also associated with a significant increase in weight
by 2.7 kg (95% CI; 1.15–2.41) vs. 1.0 kg in the placebo group over an
8-week period [37].
Mood stabilizers (primarily valproic acid, lamotrigine, and
levetiracetam) have been evaluated for their ability to manage irritability
and aggression in ASD. These agents are primarily used for their
antiepileptic properties and their mechanisms of action are varied.
Valproic acid/divalproex sodium is the most studied mood stabilizer in
ASD. Two RCTs (n=27, ages 4–15 years; and n=30, ages 6–20 years,
respectively) have yielded conflicting results [38,39]. In fact, Hellings
et al reported no changes in the ABC irritability subscale [38]. However,
this study was limited by high intra- and inter-participant variability in
aggression frequency and severity, which impacts the power of the study.
Interestingly, a large number of patients randomized to drug chose to
stay on medication at the end of the trial.
Hollander et al used the CGI-Improvement scale and the ABC to assess
irritability in response to divalproex [39]. A 62.5% positive response
rate was noted in the divalproex group vs. 9.09% in the placebo group
(Fischer’s exact, P=0.008), with an odds ratio of 16.66. There was also a
decrease in the ABC irritability subscale scores (P=0.048). Adverse events
differentially affecting the valproate group included insomnia, skin rash,
headache, and agitation. Effects on weight gain and uncommon effects
on blood counts, liver function, pancreatic function, as well as hyper-
ammonemic encephalopathy have been reported elsewhere. Lamotrigine
and levetiracetam have shown no effect on irritability or global function-
ing in children with ASD [40,41]. Thus, the overall evidence for mood
stabilizers in the management of irritability in ASD is equivocal.
Naltrexone, an opioid antagonist, also has some data to support
potential efficacy for irritability and self-injury at an optimal dose of
1.0 mg/kg/day, based on small RCTs [42,43]. For example, Campbell
et al (n=41 children) demonstrated a significant reduction in hyperactivity
(P=0.0002) and a trend toward decreased self-injurious behavior that did
not reach statistical significance [42]. Willemsen-Swinkels et al showed a
reduction in hyperactivity (P=0.003) and irritability (P=0.048) based on
scores on the ABC in 23 children treated with naltrexone 1 mg/kg [43].
A series of small, unreplicated trials have shown some benefit for
a variety of additional compounds over placebo for the treatment of
irritability in ASD. These include clonidine [23], methylphenidate [2],
amantadine [44], clomipramine [45], pioglitazone [46], levocarnitine [47],
and pentoxifyline [48], and this remains an area of active research.
Summary of evidence: treatment for irritability, aggression, self-

injurious behavior symptom cluster
There is clear evidence to support the use of atypical antipsychotics
risperidone and aripiprazole for the management of irritability and
aggression in children and youth with ASD. This is limited, however, by
significant weight gain and risk of drug-induced metabolic adverse events.
Other atypicals often used for this purpose do not have adequate data to
support their use yet. Evidence from mood stabilizers such as divalproex
sodium and agents such as naltrexone suggests that they may decrease
irritability in ASD but large clinical trials are needed.
Repetitive behaviors, obsessions, and compulsions

symptom cluster
The core behavioral symptoms of ASD include restricted, repetitive pat-
terns of behaviors, interests, or activities [1]. Repetitive behaviors in ASD
tend to not be distressing on their own to the individual, although they
may become distressing if interrupted. This behavior domain tends to be
accompanied by general rigidity around rules and routines, producing
distress around transitions or when flexibility is required. These behaviors
differ from repetitive behaviors seen in obsessive compulsive disorder
(OCD), which typically involve sequencing activities, checking, and order-
ing compulsions, and tend to be egodystonic. Still, at times it is difficult to
differentiate repetitive behaviors that are specific to ASD versus OCD-like
behaviors, especially in individuals with limited communication abilities.
Selective serotonin reuptake inhibitors

At least six RCTs have been conducted to evaluate the efficacy of selective
serotonin reuptake inhibitors (SSRIs) on repetitive/stereotyped behaviors
in ASD, although most have used small patient populations (n=12–149)
[45,49–52]. An early study (n=12) evaluated the efficacy of clomipramine
for treating repetitive stereotyped behaviors with a mean dose of
152mg per day, which showed a reduction in Modified Comprehensive
Psychopathological Rating Scale OCD subscale (P=0.001) [49,53].
Remington et al evaluated the efficacy of clomipramine vs. haloperidol
vs. placebo and found no changes on the ABC stereotypy subscale score
for clomipramine [45]. Interestingly, only 37.5% of participants completed

the clomipramine arm due to adverse events, whereas 69.7% and 65.6%
completed the haloperidol and placebo arms, respectively.
A small RCT of fluoxetine in children with ASD showed some
superiority over placebo [50]. However, the largest SSRI study (n=149)
in ASD to date showed no effectiveness for citalopram in the manage-
ment of repetitive behaviors [51].
A Cochrane review of SSRIs for repetitive behaviors in children
with ASD suggested no benefit for this class of medications in this
domain [54]. In the case of adults with ASD, there is some suggestion
of efficacy for fluoxetine and fluvoxamine based on scores from the
Yale-Brown Obsessive Compulsive Scale in two small RCTs [52,55,56].
Lastly, secondary analysis of the risperidone and aripiprazole trials have
shown evidence of efficacy for reducing repetitive behaviors compared
to placebo [7,57]. As noted above, the risk-to-benefit ratio should be
examined every time such medications are prescribed to children and
adolescents, especially for off-label use.
Anxiety and affective instability symptom cluster

Pharmacotherapy of anxiety in ASD is a very under-researched area. While
there is evidence for using SSRIs, tricyclic antidepressants, and benzodi-
azepines for the management of anxiety in typically functioning children,
there are no RCTs evaluating the efficacy of medications on symptoms of
anxiety in ASD. Thus, clinicians need to use their own judgment when pre-
scribing based on the evidence generated from children with anxiety and no
neurodevelopmental impairments. Behavioral/cognitive-behavioral inter-
ventions remain the first-line of therapy to address anxiety in any child
or youth.
Sleep problems
Sleep problems are present in up to 80% of children with ASD. Common
reported challenges include circadian rhythm sleep disorders, parasomnias,
insomnia, hypersomnia, sleep-related movement disorders, and abnormal
objective sleep patterns. Melatonin has been the only medication evalu-
ated via RCTs that has shown efficacy in reducing sleep-onset latency
and decreasing night-time awakening. A systematic review identified

that melatonin improves sleep duration by 73 minutes in the treatment
group compared to 44 minutes with placebo, and increases sleep latency
by 66 minutes (39 minutes for placebo) [58]. There was no impact on
night-time awakenings [58].
Monitoring
It is important that clinicians monitor adverse events and metabolic
complications that may occur with pharmacological agents used in the
management of associated symptoms of ASD. Monitoring of stimulants
and nonstimulants involves measurements of weight, height, heart rate,
and blood pressure. α2-agonists can cause hypotension and monitoring
of blood pressure is recommended. Antipsychotics can cause significant
weight gain, extrapyramidal side effects, hyper/hypoprolactinemia,
hyperlipidemia, and glucose abnormalities. Monitoring of weight, body
mass index, lipid profile, fasting glucose level, prolactin levels, and
evidence of extrapyramidal side effects using the AIMS [59] or a similar
scale is advised (Table 5.1).
Pringsheim et al [60] provide an excellent review of evidence regarding
the above recommendations, advising on second generation antipsychot-
ics in children. Several bodies, such as the Autism Treatment Network
and the Canadian Alliance for Monitoring Effectiveness and Safety of
Antipsychotics in Childhood (CAMESA), have produced guidelines for
such monitoring [61]. The Academy of Child and Adolescent Psychiatry
(AACAP) has recently also published a practice parameter for assessment
and treatment of children and adolescents with ASD, but do not include
monitoring guidelines specific for this population [62].
Complementary and alternative medications

Although frequently used, evidence supporting the use of complementary
and alternative medications is still lacking. For a review of complemen-
tary and alternative medicine treatment in ASD and a practical guide
consider two reviews: [63,64]. The level of research available is variable
and efficacy is not established for most complementary and alternative
medicine treatments.
Symptom domain Formulation Dosing recommendations* Baseline work-up Adverse events Monitoring Clinical pearls
– Medication choice
Hyperactivity/inattention
– Methylphenidate Immediate-release: Consider: CNS: Must track: Contraindicated
Oral solution: Starting dose: 2.5 –5 mg BID ECG and cardiac Irritability Weight in children
1 mg/mL consult if there is with structural
Increase by: 2.5–5 mg/24 hr Decreased appetite Height
a family history abnormalities, MAOI
Tablet: weekly Difficulty falling asleep BP
of cardiac illness use
5 mg,10 mg, Dose range: 5.0–60 mg/day OR
and subject has an Emotional outburst BMI There is initial growth
15 mg 0.25–1.0 mg/kg/day (divided
underline cardiac Social withdrawal delay (weight and
SR: 10–20 mg doses)
pathology height) but will
Drowsiness Consider:
LA: 10–40 mg Maximum dose: 2 mg/kg/24 hr normalize over time
or 60 mg/24 hr CBC if subject
Osmotic CR: Not indicated in
Baseline HR, BP, has pallor on
18–54 mg GIT: children <5 years
weight, height, BMI examination
CR: 10–50 mg Extended-release: Abdominal pain May lower seizure
due to risk of
Starting dose: 10–20 mg po Nausea/vomiting nutrition-based threshold
QAM Nausea anemia Consider psychiatric
Increase by: 10–20 mg weekly disorders if psychosis
Dry Mouth
precipitated with use
Maximum dose: 60 mg/day

Tics may/may not be
CVS: exacerbated
Tachycardia
Palpitation
Hypotension
Hypertension
Table 5.1 (continues opposite).

- Atomoxetine Capsules: Children <70 kg: Consider: CNS: Must track: Atomoxetine may
10 mg, 18 mg, Starting dose: 0.5 mg/kg/day Baseline HR, BP Fatigue HR take 4-7 weeks before
25 mg, 40 mg, therapeutic effects
Increase to 0.8 mg/kg/day then Difficulty falling asleep BP
60 mg are seen
up to 1.2 mg/kg/day ÷ OD or Emotional lability
BID Should discontinue
any MAOI agents
Maximum dose: 1.4 mg/kg/day
GIT: before starting
or 100 mg/day, whichever is less
Decreased appetite Evidence supporting
Children >70kg:
impact on
Nausea/vomiting
Starting dose: 40 mg/day hyperactivity and
Nausea inattention
Increase to: 60 mg/day then up
to 80 mg/day ÷OD or BID Weight loss Some anti-anxiety
Maximum dose: 100 mg/day ÷ properties (mild)
OD or BID CVS:
Tachycardia
Increase in doses can occur Rhinitis
minimum 3–10 day intervals
Table 5.1 (continues overleaf).

– Clonidine Tablet: Starting dose: 0.05 mg/day QHS Consider: CNS: Must track: Evidence supporting
0.1 mg, Increase by 0.05 mg/day every Baseline HR, BP Sedation HR impact on
0.2 mg, 3–7 days BP hyperactivity
0.3 mg Maximum dose: 0.4 mg/day CVS: Evidence to support
some impact on
Hypotension
irritability
Titrated dosing should be
divided as TID-QID Some anti-anxiety
properties (dosing at
0.15–0.5 mg/day)
For extended release:
Rebound
Starting dose 0.1 mg QHS
hypertension with
Increase by 0.1 mg (bid dosing) discontinuation or
Maximum dose: 0.4 mg/day with only OD dosing
– Guanfacine XR Tablet: Starting dose: 1 mg/day OD Consider: CNS: Must track: Evidence supporting
1 mg, 2 mg, Increase by: 1 mg/week Baseline HR, BP Sedation HR impact on
3 mg, 4 mg Maximum dose: 4 mg/day OD Fatigue hyperactivity
BP
Insomnia Evidence to support
some impact on
irritability
CVS:
Precaution in hepatic
Hypotension
or renal failure
Bradycardia
Syncope
Table 5.1 (continues opposite).

Irritability/aggression
– Aripiprazole Tablet: Starting dose: 2 mg/day OD Consider: Metabolic: Monitor risk Can lower seizure
2 mg, 5 mg, Increase by: 2–5 mg every week ECG Hyperlipidemia benefit ratio at threshold
10 mg, 15 mg, each visit Nausea can occur at
Maximum dose: 15 mg/day Ascertain family Diabetes mellitus
20 mg, 30 mg OD (average dose in autism history risk for lower doses and may
Weight gain
trials:5.0–7.5 mg/day) diabetes mellitus, Blood work every improve with dose
Hyperglycemia increase
hyperlipidemia and 3–6 months for
cardiac pathology the first year Weight gain noted up
Bloods; Fasting Other: to 2 kg in 2 months
glucose, HbA1c, Orthostatic Monitor for Low prolactin levels
lipid profile, liver Hypotension extrapyramidal noted, its significance
enzymes, prolactin side effects at is not yet established
Drowsiness
level all visits
Extrapyramidal side
Baseline HR, BP,
effects
weight, height, BMI,
Monitor weight,
waist circumference
BMI, BP at each
Baseline evaluation visit
of evidence of extra
pyramidal side
effects
Table 5.1 (continues overleaf).

Irritability/aggression
– Risperidone Oral solution: Starting dose: 0.25 mg/day Same as aripiprazole Same as aripiprazole Same as Significant weight
1 mg/ml given OD or BID aripiprazole gain associated with
Increase by: 0.5–1.0 mg every risperidone up to
Tablet:
week 2.7 kg in 2 months
0.25 mg,
Maximum dose: 3.5 mg/day in Elevated prolactin
0.5 mg, 1 mg,
children and up to 4 mg/day in levels noted
2 mg, 3 mg,
4 mg, 5 mg adolescents
Sleep
– Melatonin Over the Starting dose: 2 mg/day given None indicated Rare: Review sleep Ensure sleep routine is
counter, at night Abdominal cramps history and in place
multiple Increase by: 2–3 mg as needed sleep hygiene Rule out an organic
Fatigue
preparations techniques if no cause for sleep
Maximum dose: up to 10 mg Headache response noted problems (eg, sleep
reported in studies, no
Irritability apnea)
consensus on maximum dose
noted. Ensure room is quiet,
dark to help with

initiating sleep
Table 5.1 (continued) Medication dosing and monitoring recommendation for use in autism spectrum disorder (ASD) for pediatric patients, based on symptom-based
approach. *dose range reflects typical dosing within the pediatric population. BID, twice daily; BMI, body mass index; BP, blood pressure; CBC, complete blood count;
CNS, central nervous system; CR, controlled release; CVS, cardiovascular system; ECG, electrocardiogram; FR, fast-release; GIT, gastrointestinal tract; HbA1c, glycated
hemoglobin; HR, heart rate; LA, long-acting; MAOI, monoamine oxidase inhibitors; OD once-daily; SR, slow-release; TID, thrice-daily; XR, extended-release; QAM, every day
before noon; QHS, every night at bedtime; QID, four times daily.
Conclusions
Given the lack of translation of basic science findings into molecular
targets for drug development at this time, medications are used to treat
associated symptoms of ASD in an effort to remove barriers and facilitate
learning that is provided through conventional teaching settings such as
school, or from behavioral and/or psychosocial interventions. Careful
monitoring of all medications is necessary as per available guidelines.
With the explosion of genomic findings and data from systems neuro-
science, a series of molecular targets present themselves and several
clinical trials are currently underway with the aim of addressing core
symptom domains in ASD for the first time. Still, given that ASD is a
neurodevelopmental disorder of skill acquisition (and maintenance),
existing and future medication management will always need to be paired
with effective educational, behavioral, and/or psychosocial interventions
so that they can facilitate skill acquisition.
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Chapter 6
Behavioral and educational

interventions
Isabel M Smith, Susan E Bryson

By the end of this chapter, readers will be able to identify:
• elements of evidence-based approaches to early intervention;
• important considerations for managing maladaptive behavior;
• key elements of effective social skills interventions;
• considerations relevant to academic programs for children, youth
and young adults with autism spectrum disorder (ASD); and
• service needs for adults with ASD.
Following a diagnosis of ASD, parents understandably seek recommen-

dations about treatment for their child. Advice regarding intervention
will depend on the age and presentation of the individual; in particular,
his/her developmental level and the severity of ASD symptoms. Globally,
the goals of behavioral and educational interventions for individuals
with ASD are to:
• facilitate learning and acquisition of skills that meet individual and
family needs;
• eliminate or reduce behavior that may interfere with such learning; and
• enhance quality of life for all family members.
The heterogeneous presentation of ASD becomes more salient with age.
This is at least in part because those diagnosed youngest tend to be among

the most severely affected; hence, similar intervention targets and methods
may be appropriate very early in development. For example, a program
serving toddlers with ASD likely will have the acquisition of effective
language/communication skills as a central target of intervention. In
contrast, by the early school years, diagnosed children will range from
those with significant intellectual disability and limited communication
skills to children who are highly verbal but socially and behaviorally
atypical, with treatment needs varying accordingly.
Behavioral interventions
In general, interventions found to be effective in ASD are based on the
empirically-derived principles of learning [1]. The field of applied behavior
analysis (ABA) is dedicated to the application of strategies based on learn-
ing principles to address problems in human behavior [2]. ABA delineates
procedures that either increase or decrease behavior, in the case of desirable
(adaptive) or interfering (maladaptive) forms of behavior, respectively.
The three-term contingency (antecedent-behavior-consequence [A-B-C])
is a fundamental construct in ABA, and manipulations of this contingency
(eg, use of reinforcing consequences, which produce increases in the pre-
ceding behavior) form the basis of ABA procedures. ABA-based teaching
strategies vary in how readily they can be implemented without exten-
sive technical expertise and the context in which they can be carried out.
As an extreme example, discrete trial teaching (DTT) involves many
repetitions of precisely defined A-B-C sequences (“massed trials”) and
is typically conducted in controlled settings (eg, a quiet room with only
the child and therapist present). In contrast, “naturalistic” ABA-based
procedures capitalize on opportunities for teaching that are present in
daily activities in typical environments such as the home, preschool, or
school [3]. Some evidence supports both approaches; the critical but not
yet adequately addressed question is which ABA procedures are best suited
for which specific forms of behavior in which contexts, and for which
individuals [1,3]. One important challenge in this field is that much of
the high-quality evidence is derived from single-subject design studies.
This research design has established the efficacy of many component
B E H AV I O R A L A N D E D U C AT I O N A L I N T E R V E N T I O N S • 65
ABA-based procedures used to address behavioral deficits and excesses,

including those associated with ASD [4]. However, further research
is needed testing the overall efficacy of programs that combine these
procedures, as well as the effectiveness of service delivery models that
implement treatment at the community level.
Early intervention
As an example, in most jurisdictions in North America, specialized early
intervention programs are available for preschoolers diagnosed with
ASD. Intervention programs for young children with ASD are often
characterized as either comprehensive (multiple developmental domains
are addressed within the program), or specific (targets of treatment are
more focused) [3]. Many comprehensive programs are variants of the
model developed at the University of California at Los Angeles (UCLA)
by Lovaas, a pioneer in the use of behavioral methods to treat ASD [5].
These early intensive behavioural intervention (EIBI) programs may be
referred to as based on the "UCLA", "Lovaas", or "Young Autism Project"
model [6]. These are often erroneously called "ABA programs". (Note
that, as described above, ABA refers to a scientific discipline rather than
to any specific intervention model and is not ASD-specific).
Numerous systematic reviews and meta-analyses have concluded that
EIBI programs based on the UCLA model yield improvements in cognitive,
language, and adaptive functioning for many children with ASD (see [7,8]
for a recent overview of meta-analyses and Cochrane review). The factor
associated with the best outcomes for children appears to be the quality
of EIBI, as evidenced by expert supervision and formal monitoring of
fidelity to the treatment procedures [7]. However, although this is the best
available information, the quality of the evidence is low when evaluated
against rigorous standards [8]. The inherent difficulties in conducting
randomized controlled trials (RCTs) of such complex and long-term (2-
to-4-year RCTs) means that few well-controlled efficacy trials exist [9].
Other limited evidence on the effectiveness of early intervention programs
for preschoolers with ASD comes from community-based programs. For
example, data from Canada and Sweden suggest that children’s outcomes
can be enhanced through wide-scale implementation of well supervised

ABA-based intervention programs [10–14].
Only one study has compared the efficacy of three high-quality pre-
school programs for children with ASD, which involved comparing two
well-known intervention programs (Treatment and Education for Autistic
and Communication Handicapped [TEACCH] and Learning Experiences
and Alternative Program for Preschoolers and their Parents [LEAP]) with
a control program that did not espouse a specific treatment model [15].
Each program combined elements, including behavioral strategies (eg, rein-
forcement of desirable behavior) and other components. For example, the
TEACCH program entails considerable emphasis on organizing the child’s
environment to provide concrete cues to appropriate behavior (eg, pro-
viding designated locations for tasks-to-be-completed and for finished
activities, comparable to ‘in’ and ‘out’ boxes). Children enrolled in all three
programs showed improvements in multiple areas of functioning after
one year of treatment; there were no significant differences in outcomes
across programs [15]. These results suggest that elements common to
high-quality programs for preschoolers with ASD may be more critical
than the specific aspects that differentiate them (Table 6.1).
As the age of diagnosis of ASD has decreased, a corresponding need has
become evident for forms of intervention tailored to the needs of toddlers.
One such program, the Early Start Denver Model (ESDM), has been shown
to produce marked improvements in children’s communication and other
skills [16]. The ESDM incorporates naturalistic ABA-based strategies
within a developmental framework and has the virtue of being manu-
alized and therefore accessible to a wide range of potential users [17].
Parent education and training

One component that is common to effective early interventions for ASD
is the involvement of parents [18]. In some EIBI models, this involvement
may entail parents acting as therapists in structured DTT sessions [19].
Other treatment models promote parents’ use of naturalistic ABA-based
methods such as Pivotal Response Treatment which can be readily learned
by parents and incorporated into everyday routines [20–22]. Children’s
ability to use skills across contexts (ie, generalization) is maximized by
Qualifications and In addition to formal early childhood development and/or

supervision of staff special education qualifications, experience working with
children with ASD with similar characteristics is important.
A high staff:child ratio allows individualized attention to the
needs of the child with ASD.
Environment A calm, organized physical environment with opportunities for
individual, small group, and large group play.
Program content/targets A program that addresses the key needs of young children
of intervention with ASD by placing emphasis on functional communication
and language skills, facilitating social interaction, and the
development of daily living skills. The program should have
well-articulated procedures for supporting skill acquisition
and managing behavior problems.
Intervention methods; A program that utilizes systematic teaching by using
monitoring of fidelity of established behavioral principles and other evidence-based
treatment strategies to address developmentally appropriate goals.
Intensity of intervention A program that engages children in planned activities for
a substantial proportion of waking hours, whether in one-
on-one therapy, structured group activities within a daycare
or preschool, and/or giving parents the skills to teach their
children in the context of daily routines at home.
Table 6.1 Key considerations for choosing an intervention program for a preschooler with an
autism spectrum disorder. ASD, autism spectrum disorder.
the use of naturalistic interventions and parent training, which combine

to enable children to practice skills throughout daily life [23].
Parent training can be accomplished in group format [24] or via
individual coaching [25]. A 2013 meta-analysis demonstrated that
parent-mediated interventions may yield improved parent-child inter-
actions, as well as an increase children’s language skills and a decrease
in the severity of ASD symptoms [26]. However, this literature is affect-
ed by methodological and analytic weaknesses. Moreover, the effi-
cacy of the strategies that are taught to parents, and the fidelity with
which these strategies are implemented by parents, determine whether
they improve functioning. For example, an RCT evaluating a widely
implemented parent-mediated program that was designed to enhance
communication abilities of children with ASD produced no significant
overall gains in children’s communication skills, nor in parent responsive-
ness [27]. Whether these results are due to limitations in the techniques
themselves or in parents’ ability to use them effectively is a matter for
further research. However, some parent programs targeting children’s
communication may offer indirect benefits, such as improving preschool-

ers’ early social-communicative behavior with parents (eg, initiating
interactions, sharing attention) [28].
Among older (school-aged) children with ASD, parental training in
behavioral methods can be effective both in promoting positive behavior
and managing disruptive behavior [29–31]. In children with ASD who
developed severely disruptive behavior problems, reductions in non-
compliance and irritability were observed when parents were enrolled
in a 3-month manualized behavioral program [32]. In an RCT, the same
behavioral program produced some additional benefit when evaluated
as an adjunct to a pharmacological intervention (ie, risperidone) [33].
Interventions for disruptive behavioral problems

As a consequence of their limited communication skills and difficulties
with behavioral flexibility (eg, coping with change or the unexpected), as
well as high anxiety and possibly atypical reactions to sensory experiences,
individuals with ASD are at increased risk for displaying disruptive
behavior problems [18]. These may be manifested as tantrums, aggression,
property destruction or self-injurious behavior.
Positive behavior (interventions) and support (PBS/PBIS) [34] is
an approach to addressing behavior problems that emphasizes not only
consequences for undesirable behavior (“C” in the A-B-C contingency)
but also antecedents (“A”). That is, a major focus of PBIS is teaching skills
to individuals and engineering their environments so as to prevent the
circumstances that precipitate problematic behavior. The process of deter-
mining the antecedent conditions associated with the behavior problem
(and the reinforcing consequences) is called functional behavioral
assessment or functional analysis [35]. For example, a child may learn
to engage in self-injurious behavior such as banging her head on her desk
because adults reliably remove the requirement to comply with a difficult
task. On the other hand, head or earache pain might be associated with
such behavior. Understanding the function of the behavior permits a
tailored approach to correcting the problem (eg, teaching skills required
to master a task; treating a physical problem; Table 6.2). Timely imple-
mentation of well-designed behavioral interventions may reduce the
•• Rule out underlying medical causes for problem behavior (eg, ear or dental pain).
•• Look for patterns in order to identify its function(s) (when, where, with whom does the
behavior typically occur? What happens immediately before and after the behavior?).
•• Consider consultation with a professional who is trained in behavior analysis and
development of behavioral intervention programs (eg, Board Certified Behavior Analyst;
some specialized psychologists; some special educators).
Table 6.2  Key considerations for managing behavior problems in individuals with autism
spectrum disorder.
need for psychoactive medications, which are commonly employed for

disruptive behavior in individuals with ASD (see Chapter 5).
Social skills interventions

One of the most pressing areas of need for all individuals with ASD is
the enhancement of the ability to engage in flexible and satisfying social
interactions, especially with peers. Group social skills interventions are
often offered to children and youth with ASD, especially those who are
more intellectually able. There is some evidence to support this practice. A
meta-analysis of five RCTs demonstrated positive effects on overall social
competence, and to a lesser extent, quality of life measures [36]. Transfer
of learned skills to contexts outside the social skills training group is a
major challenge for individuals with ASD. Therefore, it is critical that
social skills programs explicitly address generalization to everyday set-
tings. A meta-analysis of 115 studies of social skills interventions that
used single-case research methods (rather than RCT designs), involving
343 participants with ASD, similarly suggested benefit [37]. Many studies
reviewed did not specify treatment parameters sufficiently well to allow
recommendation of any particular approach. However, recent data on the
Program for the Education and Enrichment of Relational Skills (PEERS)
indicate that the social skills of school-aged children [38], adolescents [39],
and young adults [40] with ASD can be improved with participation in
this manualized parent- /caregiver-assisted program [41,42].
Another promising avenue for teaching social (and other) skills is to
engage typically developing same-aged children/youth as intervention
agents for their peers with ASD. Such peer-mediated interventions
have shown positive effects. A meta-analysis of 45 studies conducted
using single-subject research methods indicated that peer-mediated
approaches produced positive outcomes for a range of targets, including

social interactions [43]. Typically developing school-aged children can
not only serve as positive role models for children with ASD, but can be
taught to use simple strategies during enjoyable play activities to elicit
more appropriate social behavior from their peers with ASD (Table 6.3).
Indeed, an RCT has demonstrated the superiority of a peer-mediated
social skills intervention over an alternative program in which children
with ASD in Grades 1–5 received direct instruction from an adult [44].
•• Involvement of peers is important but systematic teaching of specific skills, rather than mere
exposure to peers, is necessary for learning social skills.
•• Social skills are best developed with peers and during preferred activities.
Table 6.3  Key considerations for social skills programs for children with autism spectrum disorder.
Educational interventions
It is important to ensure that both academic and non-academic goals
are incorporated into individual educational plans (IEPs) or individual
program plans (IPPs) for children with ASD. These plans may resemble
programming for preschooolers with ASD, particularly among the more
severely affected. However, other more able children with ASD will be
served within inclusive settings with relatively minor modifications to the
regular curriculum. Contrary to some claims, no specific profile of cognitive
skills is associated with ASD. Although a pattern of lower verbal cognitive
skills relative to nonverbal performance skills is common, this ‘nonverbal
advantage’ is by no means universal. Indeed, other individuals with ASD
may show the opposite pattern; that is, relatively stronger verbal abilities
[45]. Yet others may show no significant discrepancies between verbal and
nonverbal abilities. Other aspects of cognition are also variable in ASD;
slow processing and problems with executive functions (eg, attentional
control, working memory) are common [46] but vary in severity.
The prevalence of intellectual disability (ID) in ASD has been a moving
target as the definition of ASD has evolved in recent decades. However,
a recent estimate is that about 40% of children with ASD demonstrate
comorbid intellectual disability [47]. Many individuals with ASD but
without ID meet criteria for a specific learning disability (eg, in reading
or math). The newly revised Diagnostic and Statistical Manual of Mental
Disorders, 5th edition (DSM-5) [48] provides a framework for formal

recognition of these characteristics by directing diagnosticians to specify
the additional disorders/disabilities that may accompany ASD.
Given these considerations regarding intellectual abilities, academic
programming should follow from the individual profile (ie, cogni-
tive and academic strengths and weaknesses) defined in a formal
neuropsychological/psychoeducational assessment. To optimize self-
esteem and emotional well-being, academic programming should focus
on developing the student’s strengths and interests rather than focus-
sing exclusively on the remediation of deficits. Other basic educational
principles are related to the need to adjust teaching methods to accom-
modate characteristics associated with ASD such as difficulty with
generalization, especially as it pertains to application of knowledge in
real world situations. That is, for many skills, explicit teaching in the
context in which the skill must be used is necessary for the individual
to demonstrate competence.
In some jurisdictions, specialized academic programs, classrooms,
or even schools are available to meet the needs of children and youth
with ASD. Ideally, educational programs for children and youth with
ASD will address social and adaptive behavior needs (including those
related to 'street-proofing' and personal safety), as well as academic
subjects. Guidelines for educational best practices that address all of these
areas are available from two recent major initiatives in the US [3,49].
Unfortunately, the high prevalence of bullying of children and youth
with ASD (recently estimated at 46% of adolescents [50]) has made this
form of victimization a critical consideration in educational contexts for
those with ASD and their peers [51]. Specific effectiveness of mainstream
bullying prevention programs for youth with ASD is unknown [50]; some
have argued that bullying prevention and monitoring strategies should
be part of the student’s IEP, as well as a school-wide effort [52].
Post-secondary education
Educational opportunities and supports for older adolescents and young
adults have come to the fore in recent years, as increasing numbers of
more able individuals with ASD graduate from secondary schools. As
yet, there is little evidence to support specific educational practices in

this age range. However, the literature concerning other developmental
and learning disorders provides some direction. Key factors include early
assessment and preparation for realistic post-secondary options for the
individual. Transition planning ideally begins in early adolescence and
includes teaching skills related to self-determination (defined as the
accumulation of skills, attitudes and beliefs enabling control over one’s
own life) as part of the educational curriculum (Table 6.4) [53]. Teaching
such skills may be particularly essential yet uniquely challenging for
individuals with ASD, for whom both sense of identity and ability to
self-evaluate may be reduced relative to their peers [54], yet guidance
from the literature is scarce.
•• Educational programs must be individualized, based on profiles of strengths as

well as weaknesses.
•• Both academic and non-academic (eg, social, adaptive behavior) goals should be part of the
individual plan, as appropriate.
•• The future usefulness of any given skill to that individual should be taken into account before
it becomes part of the teaching plan.
•• Vigilance on the part of educators, parents and others is essential to prevent or address
potential bullying/victimization.
•• Formal planning for educational transitions (to middle or junior high school, to high school,
to adulthood) should begin well in advance of the anticipated transition.
Table 6.4 Key considerations for educational programs for children with autism
spectrum disorder.
Intervention for adults

Despite advances in intervention for younger individuals with ASD, data
on outcomes in adulthood remain sobering. A recent epidemiological
study in the UK showed that adults with ASD experienced high levels of
unemployment and other economic disadvantages, as well as low levels
of social support [55]. Reviews of research pertaining to services for
adults with ASD highlight the anticipated increase in the already high
need for services, accompanied by serious gaps in knowledge of effec-
tive practices [56,57]. As at all stages of the lifespan, the needs of adults
with ASD vary enormously depending on level of function and presence
of comorbid conditions [58]. Even among the most intellectually able
persons with ASD, continuing supports are typically needed in work or
other vocational settings. Thus, preparatory programs and supports are

needed to enable participation in vocational activities (at whatever level
meets individuals’ abilities and interests), as are social skills programs
and opportunities for social and community participation (Table 6.5).
•• Given the limited research base, extrapolation from principles derived from interventions for
younger individuals with autism spectrum disorder (ASD) is warranted.
•• The need to respect adults’ preferences regarding vocational activities and other life choices,
and to ensure that programming is age-appropriate and contextually relevant, renders this
period particularly sensitive for design and provision of intervention services.
•• Access to mental health services is critical for adults with ASD.
•• Support from individuals other than family members becomes an important consideration
for addressing the long-term needs of adults with ASD. This issue is best addressed
through early planning for transition to adulthood that recognizes the need to maximize
independent living skills while family supports are still available.
Table 6.5  Key considerations for interventions for adults with autism spectrum disorder.
Appropriate residential options are also a critical issue for most

adults with ASD, especially those with comorbid ID. A systematic review
of psychosocial interventions for adults with ASD identified a range of
single-case design studies of ABA-based interventions, and a few studies
aimed at improving aspects of social cognition, as well as evaluations of
a variety of community-based programs [59]. Overall, the evidence-base
is limited and the majority of studies lack rigor. However, when there is
a need to teach specific skills, or to reduce problem behavior, in order
to accomplish valued goals for adults with ASD, the same principles of
teaching and learning as described earlier for younger individuals apply
equally to adults.
Treatment for associated mental health problems such as anxiety
or depression is among the greatest areas of need for adults with ASD
(see Chapter 3). Mental health services are also essential for adults
with comorbid ID, who may present with aggressive behavior. Access to
mental health practitioners with expertise in adapting psychotherapeutic
approaches to the needs of clients with ASD is improving in major centers
but remains a challenge in many areas. Experts highlight that the lack
of coordination of the various services needed by most adults with ASD
(eg, vocational, residential, recreational, mental health) is yet another
service gap [57]. This challenge has been addressed for some adults with
ASD and ID in the context of community, residential, and vocational

settings such as the Carolina Living and Learning Center, part of the
statewide TEACCH system [60].
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Chapter 7
Autism spectrum disorder and the

family: examining impacts and the
need for support
David B Nicholas and Christopher Kilmer

• understand psychosocial impacts of autism spectrum disorder
(ASD) on individuals and families;
• understand ways that families navigate ASD-associated care;
• gain knowledge about family experiences in the context of
transition and lifespan issues; and
• identify emerging questions and priorities for understanding
family issues and supporting family wellness.
Introduction
ASD is a pervasive condition that has a profound and prolonged impact
on families. This chapter offers an overview of selected literature identi-
fying family experiences of ASD, with implications for clinical care and
support. An argument is made for greater person- and family-centered
care, including reflective practice that enables heightened understand-
ing and support for families with the aim of optimal individual and
family experience.

Impact of autism spectrum disorder on families

ASD presents many challenges that can profoundly affect family life. The
heterogeneity of ASD and the uniqueness of families cumulatively lead to a
wide variety of experiences and outcomes. Outcomes are further affected
by external factors and social determinants such as socioeconomic status,
funding availability for services, geographic location and proximity to
services, parental availability for family-mediated intervention, broader
community support, and a range of other considerations.
Notwithstanding this variation of family experience, ASD invariably
affects individuals within the family and the family as a whole. As an
example, external factors such as funding limitations, lengthy waiting
times, and strict eligibility requirements affect the roles that parents play
in accessing and delivering interventions. In seeking services, parents
typically assume roles of advocate and coordinator of their child’s care,
which imposes demands on parents and often relegates them to service
access pathways that are rife with confusion, uncertainty, and stress [1–3].
Emerging evidence points to qualitative differences in parenting a
child with ASD. Studies increasingly attest to nuanced tasks associated
with parental care for a child with ASD, manifested as extraordinary
work that can span day- and night-time hours, often leaving parents
sleep-deprived and emotionally strained [4–6].
There are current gaps in our understanding about how families make
meaning of ASD and integrate this specialized care within family life, as
seen with recent efforts to address the critical role that parents play in
the life of their child with ASD [4]. This work highlights a range of ten-
sions experienced by parents. For instance, from the initial awareness of
ASD-like symptoms in their child, parents describe difficulty obtaining
a diagnosis for their child often due to long delays for a developmental
assessment. Ironically, some of the strengths that parents may see in
their child (eg, organization of items) are often recast at diagnosis as an
illustration of differences associated with ASD. Parents’ relentless need
to advocate for services renders a complex conundrum and, in particular,
a discourse that warrants early and substantial child intervention often
in the face of restrictions and delays in obtaining funding and accessing
AU T I S M S P E C T R U M D I S O R D E R A N D T H E FA M I LY • 79
services. Using the National Survey of Children With Special Health Care
Needs, Kogan et al [7] compared groups of 3–17-year-old children with:
• special health care needs and ASD;
• special health care needs and other developmental, behavioral, or
emotional challenges; and
• other special health care needs.
The group of parents whose child had special health care needs and
ASD were more likely to report substantial financial costs, including a
reduction of employment in order to care for their child [7]. A ten-year
longitudinal ethnographic study exploring the psychosocial elements of
parenting a child with ASD demonstrated that, while parents exhibited
high levels of psychological distress, this lessened as the child advanced in
age (although distress levels remained substantial) [8]. Career difficulties
were also experienced, more typically by mothers than fathers. While
some mothers had entered the workforce or were pursuing education,
approximately half reported being either unable to work or requiring a
restricted schedule or type of employment [8]. Parents were also found to
be concerned about a loss of family opportunity to socialize due to having
a child with ASD. Generally, and continuing over time, approximately
20% reported this as a problematic, long-standing issue.
Some problems faced by families, such as child communication and
behavioral issues in public, were reported to diminish over time; however,
in some cases, other problems developed or intensified over time, such as
parental anxiety over their child’s future or the possibility of increased
aggressive behavior [8]. Hastings and colleagues explored the coping
strategies of parents of children with ASD and found that mothers and
fathers may cope differently [9]. Yet more research is warranted to address
parental coping and differential impacts of ASD between mothers and
fathers. While these differences are hypothesized, little research has yet
examined potential differences.
Impact on parenting
Gray examined parental experience with a focus on the ongoing imposition
of stigma [8]. This construct was further differentiated as ‘felt’ and
‘enacted’ stigma. The majority of parents of a child with ASD experienced

both forms, with mothers being more likely than fathers to report stigma
[8]. Felt stigma commonly occurred when in public settings. During
these occasions, parents believed that others were judging their parent-
ing abilities. Enacted stigma was less common, being reported by about
half of the participants. It reflected forms of avoidance (eg, not being
invited to social events), members of the public staring at the family in
what was described as a ‘hostile’ manner, and individuals making rude or
hurtful comments to members of the family. Parents reported heightened
difficulties with stigma due to ASD not being a visible disability [8]. In
another study, Gray reported that while social stigma was experienced
by parents across the study’s decade-long time frame, it mattered less
to parents as time progressed [10].
Woodgate, Ateah, and Secco [5] interviewed parents of children with
ASD about their experience and the main themes that emerged included:
• 'living in a world of our own': feeling alone and isolated from peers,
family, and society, and in many cases, not having an accessible
support system of professionals;
• 'vigilant parenting': extensive and protective practices that parents
enacted, as well as viewing parenting as a team effort;
• 'sustaining the self and family': belief that a strong sense of self and
family and a healthy familial balance is beneficial to the child with
ASD; and
• 'fighting all the way': parents felt that they needed to assume an
advocacy role for their family, as well as seek to improve the system
for other families in which a child has ASD. Parent education was
highlighted as important in navigating and managing ASD in
daily life.
Bayat [11] explored the notion of resiliency among families in which a
child has ASD. Based on survey results, family resiliency was identified
as being present in families; however, this was manifested in a number
of ways. For instance, participants reported their family pulling together
and becoming more cohesive, finding meaning in the hardships they
encountered, achieving increased personal strength and ability to be
compassionate, and fostering a deeper sense of spirituality [11].
Impact on siblings
Macks and Reeve [12] explored the psychosocial and emotional adjust-
ment of siblings of children with ASD by comparing this group to a
comparison group of children whose sibling(s) did not have a disability.
Interestingly, siblings of children with ASD had a more positive view of
themselves relative to peers’ self-appraisal regarding their behavior and
intelligence [12]. However, certain demographic characteristics were
more likely to negatively affect the sibling of a child with ASD, such as
low socioeconomic status, being an only other sibling, and being older
than the child with ASD. Benson and Karlof similarly examined the
adjustment of siblings of a child with ASD compared to children without
a sibling with ASD [13]. The level of parental involvement in education
was related to positive sibling adjustment. Stressful life events, such
as financial issues and the death of friends or family members, were
reported to have an adverse effect on sibling adjustment. The quality
of 'family climate' was linked with heightened prosocial behavior [13].
Impact on grandparents
Relatively little research has examined grandparenting in ASD. Margetts
et al explored the experiences of grandparents of a child with ASD through
qualitative interviews [14]. Grandparents reported a 'parental bond,' yet
also described a burden of caring for both their grandchild with ASD
and the grandchild’s parent (ie, their adult child). Another emergent
theme comprised grandparental 'striving for answers,' as grandparents
struggled with how to best support their adult children and what role
they should play, while at the same time attempting to understand ASD.
'Keeping intact,' the final theme presented by Margetts et al, entailed
grandparental attempts to discover and establish their role within the
family, with some grandparents feeling a responsibility to keep the
family intact [14].
Navigating the transition to adulthood

As children with ASD advance toward adulthood, families are faced with
additional challenges amidst a relative dearth of information or resources
related to transitional and lifespan-based issues. Parents report varying
needs related to mental health concerns such as anxiety and depression,

sensory issues, vocation, housing, and other areas of concern. Resources
for youth and adults are integral to establishing and enabling a viable
life plan that optimizes opportunity and quality of life. Yet, parents often
have no, few, and/or underdeveloped resources [15] and face a myriad
of barriers to meaningful community engagement for their adult child.
Service systems vary across jurisdiction but are generally insufficient
to meet needs [16,17].
With multiple demands of care and a largely ‘siloed’ (ie, restricted to
particular services) adult service system in regard to funding, health care,
mental health, vocational training, and housing, parents are often left to
independently struggle in seeking, finding, and coordinating services.
Considerations following a diagnosis of autism

spectrum disorder
There is a current gap in our understanding about how families affected
by ASD move forward and reconcile their lives relative to the presence
of ASD. Little has been published on the cumulative impact of ASD on
families over time. Questions abound such as:
• How do couples navigate and mutually manage ASD in the context
of child and adolescent development?
• What is the impact of ASD on the parents’ relationship as a couple
(or other co-parenting partner configurations)?
• What strategies optimally support families as they navigate ASD
care and manage family life?
While examples of excellent care exist, there is substantial work to be
done in order to consistently offer effective supports for all families
throughout the lifespan of the individual with ASD. Understanding the
trajectory of the family requires increased family-based research. To that
end, sensitive metrics are needed to understand and monitor the impact
of ASD on the family and assess how ASD is understood and managed
in daily life. For clinicians, assessment and support services need to
more comprehensively consider the needs of the entire family. Thorough
assessment, followed by corresponding resources, would result in greater
understanding, improved outcomes, and better-supported families.
Finally, theoretically-grounded models need to be developed that

fully recognize and value the role of the family in care provision and
outcomes. Existing examples include the Bowen Theory, a family systems
approach which accounts for the interaction of subsystems and recognizes
how one member of the family influences another [18]; however, how a
person with ASD uniquely nuances this process is still largely unknown.
Further development and refinement of this and similar models may
support our quest to more fully understand how ASD affects family life
and how family functioning moderates the impact of ASD. Moreover,
critically considering and redressing structural and community barriers
associated with the social determinants of health can assist in mitigating
inequities faced by marginalized families in contemporary society.
Implications for practitioners

There is a pressing need to achieve better outcomes for families affected
by ASD. Advancement seems to entail increased investment in clinical
and community care, research, and education, with an aim of evidence-
based models of practice and capacity development. In advocating for
this advancement, several considerations emerge.
First, many individuals with ASD experience comorbid health, mental
health, and sensory issues. Given the preponderance and complexity of
these challenges in the lives of individuals with ASD and their families,
there is a need for timely assessment and proactive follow-up in effectively
responding to these comorbidities (see Chapters 3 and 4). Proactive inter-
vention is not only important for the individual with ASD but also her/his
family, which often buffers the challenges associated with these issues.
Practitioners need to carefully examine the extent to which clinical,
educational, vocational, and other community environments impose
conditions that heighten anxiety or discomfort for the individual with
ASD. Strategies to neutralize stress-inducing environments or conditions
warrant strategic planning and management. This may include new
models advancing comprehensive and coordinated care in the community.
Families have presented a range of positive and negative experiences
with ASD service providers and systems [4]. Emerging evidence high-
lights the promising effect of child and family-centered care in nurturing
constructive experiences and satisfaction for families [19]. Person- and

family-centered care offer an integral component to pediatric and adult
care; these principles inviting professional reflection on ways to foster
respect, information sharing and collaboration with families [20].
Consistent with person- and family-centered care, service providers
are well-advised to listen to parents who tend to be knowledgeable
advocates for their loved one with ASD. Parental perspectives can be
pivotal to the acquisition of case-related knowledge and astute planning.
This is particularly salient if the person with ASD is non-verbal or has
a cognitive impairment that precludes independent communication of
personal needs and wants.
Thus, training at multiple levels in ASD to complement person- and
family-centered care, is recommended. Infusing ASD and family-centered
curricula in to trainee education and professional development can increase
practitioner capacity. A multipronged capacity-building approach is sought
that includes learning opportunities for individuals with ASD, parents,
families, lay supporters, and communities, as well as interdisciplinary
education for community practitioners, medical subspecialists, and allied
health care professionals caring for related health and mental health issues
(eg, gastrointestinal issues, seizures, psychiatric concerns).
Conclusions
Understanding the strengths and challenges of individuals and families living
with ASD is critically important, as is supporting families with proactive
strategies via accessible and evidence-informed person- and family-centered
care. This invites a comprehensive and coordinated care system with defined
targets. Clearly, much work has yet to be done, but steps forward include
greater awareness of families’ experiences, priorities, and needs, and the
corresponding development of adequately funded resources for individu-
als and families. Intentionally partnering with families can take us a long
way towards building impactful relationships of engagement and support.
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17 The Standing Senate Committee on Social Affairs, Science and Technology. Pay now or
pay later: Autism families in crisis. www.parl.gc.ca/Content/SEN/Committee/391/soci/rep/
repfinmar07-e.htm. Updated March 2007. Accessed February 4, 2015.
18 Bowen Center for the Family. The Bowen theory. www.thebowencenter.org/pages/theory.
html. Accessed February 4, 2015.
19 Nicholas DB, Keilty K, Karmali K. Paediatric patient-centred care: Evidence and evolution. In,
Zlotnik Shaul R, ed. Ethics and Law in Pediatric Patient and Family-Centred Care. New York, NY:
Springer; 2014.
20 Institute for Patient- and Family-Centered Care (IPFCC). Frequently Asked Questions. IPFCC
website. www.ipfcc.org/faq.html. Accessed February 4, 2015.
Chapter 8
Future directions
Jessica Brian, Evdokia Anagnostou
With rising prevalence rates, improvements in early detection, and

increased awareness overall, autism spectrum disorder (ASD) will
increasingly be in the purview of primary care physicians and other
community practitioners. In light of these developments, primary care
providers will benefit from arming themselves with knowledge about
the state of the science in ASD and best practices for care. We now
understand ASD to have a strong genomic/epigenomic contribution
and we have an accumulation of evidence to inform earliest detection,
timely diagnosis, and behavioral interventions. Primary care providers
are tasked with understanding the most common co-occurring medical
and psychiatric/mental health conditions in individuals with ASD, and
will increasingly find themselves in a position to counsel and support
individuals and their families, and to treat these co-occurring condi-
tions. By adopting a person- and family-centred approach, care providers
will be able to appreciate the unique stressors and joys associated with
raising a child with ASD and will be better able to support not only the
families, but the individuals themselves as they develop through the
lifespan. While there remain many instances where specialists and/or
specialized teams will be needed, we increasingly recognize the essen-
tial role of primary care providers in contributing to the well-being of
individuals with ASD and their families.

Future advances
As we look ahead into the next generation(s), advances in several key
areas will have a major impact on the ASD experience for individuals
and families. These, in turn, will affect how we provide care and counsel
patients. Significant advances are on the horizon in:
• genomics/epigenomics;
• detection of very early behavioral markers;
• characterization of comborbidities;
• psychopharmacological treatments;
• behavioral interventions; and
• person- and family-centered care.
Advances in genomics/epigenomics
Significant advances have been made in recent years in our understanding
of the genomic contribution to ASD. We know that first-degree relatives
of children with ASD are at increased risk for ASD and related outcomes
themselves [1]. However, most genomic variation discovered to date in
ASD is still de novo, and evidence supports a major role of epigenomics
in the expression of ASD [2]. The more we learn about genomic varia-
tion, the closer we will come to being able to map down to metabolic
pathways, which will inform the identification of biological subgroups.
This in turn will inform the development of targeted treatments.
Advances in early detection

The average age of diagnosis remains around 4 years of age in most
industrialized nations despite impressive advances in early detection
research (eg, Autism Speaks’ Baby Siblings Research Consortium, which
includes research teams from Canada, Israel, the United Kingdom, and
the United States). A host of early risk markers have been identified as
early as 12 months of age in high-risk babies (ie, siblings of children
with ASD, who themselves are at increased risk), suggesting that the
age of detection could be significantly younger [1,3]. Earlier detection
is a priority given evidence of improved outcomes with earlier interven-
tion [4]. This is supported by current understanding of neural plasticity
which would predict the mitigation of downstream effects of biological
FU T U R E D I R E C T I O N S • 89
atypicalities in response to earlier intervention. In order to move this

work forward, we will need to determine the predictive value of these
risk markers in other at-risk and typically developing populations (eg, to
establish their specificity to ASD or related suboptimal outcomes), dis-
seminate this evidence effectively to community practitioners, provide
training opportunities in the assessment and detection of these early
signs, and promote models of service delivery that support earlier identi-
fication and diagnosis. Such advances have the potential to substantially
improve timely access to appropriate care at the earliest time points, thus
increasing the potential for optimal outcomes.
Exploring comorbidities
Both medical and psychiatric comorbidities are common in ASD. There
is still a lot of work to be done to understand whether the constructs of
these comorbidities are the same in patients with ASD as in the general
population (eg, is anxiety in ASD the same disorder as anxiety in the
general population? Are gastointestinal issues in ASD simply co-occur-
ring or linked to the pathophysiology of the disorder?). Stratification by
medical and/or psychiatric comorbidities will contribute to the success
of clinical trials research.
Developments in psychopharmacological treatments

New molecular and circuitry targets are emerging from genomics, neuro-
pathology, and systems neuroscience. The task now is to start translating
such findings into treatments that specifically address the pathophysiology
of differences in ASD. Emerging biomarker discovery will also become
critical to allow for personalization of treatments based on individual
biological and other differences.
Future developments in behavioral intervention research

Prior to recent years, the majority of evidence supporting behavioral
intervention had come from single-subject designs and smaller studies
from highly specialized academic centers. Only very recently has there
been a ground swell of evidence from larger-scale investigations,
including randomized controlled trials, meta-analyses, and wide-scale
community dissemination studies. Next steps for behavioral intervention

efforts, already emerging, include addressing the developmental needs
of babies/toddlers in the first years of life [5], the development and
evaluation of interventions based on emerging signs of risk (rather
than waiting for confirmed diagnosis), the greater inclusion of primary
caregivers (parents, grandparents, childcare providers), and models that
increase timely access to care by improving feasibility, cost-effectiveness,
portability, and ease of community implementation.
Advances in person- and family-centered care

Recent developments include the increased appreciation of the family’s
role in the lives of children with ASD, with the promise of ongoing
investigation of caregiver burden, identification of needs during transitions
throughout the lifespan, and the lived experience of individuals with ASD
and their family members. Many questions remain about the impact of
ASD on the family as a unit, on the parents’ relationship with one another,
and on individual family members, but this important area of research
is gaining traction and is increasingly recognized as a research priority.
Conclusions
As the need for ASD care has increased, so has the appreciation of
the complexity inherent in this multifactorial disorder. Heterogeneity
exists in the underlying biology, etiology, developmental progression,
behavioral presentation, individual and family experience, associated
medical and psychiatric conditions, and not surprisingly, in the response
to intervention for individuals with ASD. This complexity presents unique
challenges to individuals and their families, researchers, care providers,
and policy-makers. By working together to further propel research efforts
and improve access to timely, high quality care, we will enter the next
decade armed with the tools to reduce the burden and optimize outcomes
for individuals with ASD and their caregivers.
FU T U R E D I R E C T I O N S • 91
References
1 Ozonoff S, Young GS, Carter A, et al. Recurrence risk for autism spectrum disorders: a Baby
Siblings Research Consortium study. Pediatrics. 2011;128:e488-e495.
2 Anagnostou E, Zwaigenbaum L, Szatmari P, et al. Autism spectrum disorder: advances in
evidence-based practice. CMAJ. 2014;186:509-519.
3 Zwaigenbaum L, Bryson S, Lord C, et al. Clinical assessment and management of toddlers with
suspected autism spectrum disorder: insights from studies of high-risk infants. Pediatrics.
2009;123:1383-1391.
4 Makrygianni MK, Reed P. A meta-analytic review of the effectiveness of behavioural early
intervention programs for children with Autistic Spectrum Disorders. Res Autism Spectr Disord.
2010;4:577-593.
5 Brian JA, Bryson SE, Zwaigenbaum L. Autism spectrum disorder in infancy: developmental
considerations in treatment targets. Current Opin Neurol. 2015; 28:117-123.

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Evdokia Anagnostou · Jessica Brian

ISBN 978-3-319-03055-5 ISBN 978-2-319-03056-2 (eBook)

© Springer International Publishing Switzerland 2015

Printed on acid-free paper

Adis is a brand of Springer

Project editor: Katrina Dorn

2 Diagnosis: screening, surveillance, assessment, 5

3 Common psychiatric comorbidities and 19

4 Medical comorbidities in autism spectrum disorder 33

5 Pharmacotherapy in autism spectrum disorder 43

6 Behavioral and educational interventions 63

7 Autism spectrum disorder and the family: examining

Evdokia Anagnostou, MD, Senior Clinician Scientist, Bloorview Research

Jessica Brian, PhD, C.Psych, is a Psychologist and Clinician-Investigator

Daniel Coury, MD, FAAP, is Professor of Pediatrics and Psychiatry in the

Hospital in Columbus, Ohio. He conducts research and provides care for

Chris Kilmer, BSW, RSW, is a Research Coordinator in the Faculty

David Nicholas, PhD, RSW, Associate Professor in the Faculty of Social

Melanie Penner, MD, FRCPC, is a developmental pediatrician with an

Wendy Roberts, MD, is a developmental pediatrician who is now a

Sharon Smile, MD, completed her pediatric training at the University

Neuroscience at Dalhousie University, based at the IWK Health Centre in

Jennifer Walton, MD, MPH, FAAP, is Assistant Professor of Pediatrics in

physician in the Section of Developmental and Behavioral Pediatrics at

Lonnie Zwaigenbaum, MD, PhD, completed his pediatric training at

Ó Springer International Publishing Switzerland 2015 1

informing our approach to treatment development so that, for the first

of psychiatric and medical co-occurring conditions and approaches to

Diagnosis: screening, surveillance,

Key Learning Objectives

Assessment of autism spectrum disorder:

Ó Springer International Publishing Switzerland 2015 5

intervention [1]. Screening refers to administering and scoring a specific

Wetherby et al [16] have adopted a similar strategy with the

Team structure and function

challenges, and different team members may need to be consulted with

Team member Role

Table 2.1 Team members and potential contributions to diagnostic assessment.

connect team members across settings to allow valuable team discussions

Components of diagnostic assessment

“Sometimes families have specific things they want us to

“We will be looking at all areas of your child’s development;

It is also important to start the interaction by explaining the various

them by other people in the child’s life. It is important to solicit informa-

which are less time-consuming and can be completed between appoint-

The Childhood Autism Rating Scale (CARS-2) is a brief observational

Additional assessment components

Formulation and feedback

feedback session, it is useful for the clinician to finalize a formulation

“[Child’s name] has difficulty sharing his/her feelings with

when the diagnosis is shared. The family may require a number of

Common psychiatric comorbidities

Key Learning Objectives

Ó Springer International Publishing Switzerland 2015 19

in the general population, and that comorbid psychiatric disorders can

Prevalence of psychiatric comorbidity

anxiety (16%), generalized anxiety (15%), separation anxiety (9%), and

The DSM-5 and diagnosis of psychiatric

Maximum dose: 60 mg/day