2014 AACAP autism practice parameters jaacap · Child and Adolescent Psychiatry (AACAP) Committee...

CORRECTION

In the article, “Practice Parameter for the Assessment and Treatment of Children and Adolescents WithAutism Spectrum Disorder” by Fred Volkmar, MD, Matthew Siegel, MD, Marc Woodbury-Smith, MD,Bryan King, MD, James McCracken, MD, Matthew State, MD, PhD, and the American Academy ofChild and Adolescent Psychiatry (AACAP) Committee on Quality Issues (CQI), published in theFebruary 2014 issue of the Journal of the American Academy of Child and Adolescent Psychiatry (2014;53:237–257), on page 252, Dr. Claudio Toppelberg was mistakenly omitted from the list of expertsacknowledged for their contributions to the Parameter. Although he was inadvertently omitted, hiswork on behalf of the CQI is deeply appreciated, and we would like to correct the error andacknowledge him here. The authors and the editorial office regret the error. &

0890-8567/$36.00/ª2014 American Academy of Child andAdolescent Psychiatry

http://dx.doi.org/10.1016/j.jaac.2014.06.001

JOURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY

VOLUME 53 NUMBER 8 AUGUST 2014 www.jaacap.org 931

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Practice Parameter for the Assessment andTreatment of Children and Adolescents With

Autism Spectrum DisorderFred Volkmar, MD, Matthew Siegel, MD, Marc Woodbury-Smith, MD, Bryan King, MD,James McCracken, MD, Matthew State, MD, PhD, and the American Academy of Child

and Adolescent Psychiatry (AACAP) Committee on Quality Issues (CQI)

Autism spectrum disorder is characterized by patterns of delay and deviance in the develop-ment of social, communicative, and cognitive skills that arise in the first years of life. Althoughfrequently associated with intellectual disability, this condition is distinctive in its course,impact, and treatment. Autism spectrum disorder has a wide range of syndrome expressionand its management presents particular challenges for clinicians. Individuals with an autismspectrum disorder can present for clinical care at any point in development. The multipledevelopmental and behavioral problems associated with this condition necessitate multidisci-plinary care, coordination of services, and advocacy for individuals and their families. Early,sustained intervention and the use of multiple treatment modalities are indicated. J. Am. Acad.Child Adolesc. Psychiatry, 2014;53(2):237–257. Key Words: autism, Practice Parameters,guidelines, developmental disorders, pervasive developmental disorders

S ince the first Practice Parameter for theAssessment and Treatment of Children,Adolescents, and Adults with Autism

and Other Pervasive Developmental Disorders1

was published, several thousand research andclinical articles have appeared and the diag-nostic criteria for autism have changed. ThisParameter revision provides the opportunity toupdate the previous version and incorporatenew research. Because the extant body ofresearch was performed under the DSM-IV-TRdiagnostic schema, the evidence will be pre-sented using that terminology. This Parameteris applicable to evaluation of children and ad-olescents (!17 years of age) but often will havesome relevance to adults. This document pre-sumes basic familiarity with aspects of normalchild development and child psychiatric diag-nosis and treatment. Unless otherwise noted,the term child refers to adolescents andyounger children, and parents refers to the

child’s primary caretakers regardless ofwhether they are the biological or adoptiveparents or legal guardians.

METHODOLOGYThe first version of this Parameter was publishedin 1999. For this revision, the literature searchcovered the period from 1991 to March 19, 2013using the PubMed, PsycINFO, Cochrane, andCINAHL (EBSCO) databases. The initial searcheswere inclusive and sensitive. Search terms were acombination of MeSH headings and keywords,and the MeSH headings were adjusted to termsused by PsycINFO and CINAHL by using theirthesauri.

In PubMed the MeSH terms autistic disorder,childhood development disorders—pervasive, Asperger*,and Rett* and the keyword autism were searched.The initial search yielded 20,807 results. Then, theresults were limited to English, human, all child(0 to 18 years), and 1991 to March 19, 2013. Addi-tional limits included classic article, clinical trial,comparative study, controlled clinical trial, eva-luation studies, guideline, historical article, meta-analysis, practice guideline, multicenter study,randomized controlled trial, review, twin study,

This article can be used to obtain continuing medical education(CME) at www.jaacap.org.


VOLUME 53 NUMBER 2 FEBRUARY 2014 www.jaacap.org 237

and validation studies. The refined PubMed searchyielded 3,613 articles.

In the PsycINFO database subject headings(focused) of autism, autistic thinking, pervasivedevelopmental disorders, retts syndrome, aspergers,and keyword autism were searched. The initialsearch returned 24,875 articles and was thenlimited to English, childhood: birth to age 12yrs,adolescence: age 13-17 yrs, peer reviewed journal, and1991 to March 19, 2013. The refined PsycINFOsearch yielded 9,583 articles.

In the Cochrane Database of Systematic Re-views, keywords of autism, autistic, rett*, asperger*,or (pervasive and disorder* and develop*) weresearched without additional limits. The Cochranesearch yielded 95 articles. An additional 517 ar-ticles were retrieved from the CINAHL database,after excluding Medline articles, by searchingautistic disorder, autism, asperger syndrome, childdevelopment disorders, pervasive, and rett syndrome.

A total of 13,808 articles were identified andexported to the EndNote reference managementprogram. After removing duplicate references,the resulting yield from the comprehensivesearch was 9,581 articles.

The titles and abstracts of all articles werereviewed. Studies were selected for full textreview based on their place in the hierarchy ofevidence (e.g., randomized controlled trials),quality of individual studies, and generalizabilityto clinical practice. The search was augmented byreview of articles nominated by expert reviewersand further search of article reference lists andrelevant textbook chapters. A total of 186 articleswere selected for full text examination.

CLINICAL PRESENTATION AND COURSEAutism was first described in 1943 by Kanner2

who reported on 11 children with an apparentlycongenital inability to relate to other people butwho were quite sensitive to change in thenonsocial environment. Kanner emphasized thatthe lack of interest in people was in stark contrastto the profound social interest of normal infants.He also observed that when language devel-oped at all, it was marked by echolalia, pronounreversal, and concreteness. The children alsoexhibited unusual, repetitive, and apparentlypurposeless activities (stereotypies). Autism wasinitially believed to be a form of childhood psy-chosis, but, by the 1970s, various lines of evidencemade it clear that autism was highly distinctive.By 1980, autism was officially recognized as adiagnosis in DSM-III.3

Under DSM-IV-TR, the diagnosis of autismrequired disturbances in each of 3 domains: socialrelatedness, communication/play, and restrictedinterests and activities with onset by 3 years ofage.4 The disturbance in social relatedness isstriking and includes marked impairment innonverbal communication, peer relationships,and social-emotional reciprocity. Impairments incommunication include a delay or total lack ofspoken language (without an attempt tocompensate through other means) or, for verbalindividuals, a marked difficulty in the ability tosustain or initiate conversation, stereotyped andrepetitive (or idiosyncratic) language, and lack ofdevelopmentally appropriate make-believe orsocial play. Impairment in interests and activitiesincludes encompassing preoccupations, adher-ence to apparently nonfunctional routines or rit-uals, stereotypies and motor mannerisms, andpersistent preoccupation with parts of objects.

There is variability in the age at which childrenmay present the features essential for this diag-nosis.5 Preschool children with autism typicallypresent with marked lack of interest in others,failures in empathy, absent or severely delayedspeech and communication, marked resistance tochange, restricted interests, and stereotypedmovements. Common parental concerns includea child’s lack of language, inconsistencies inresponsiveness, or concern that the child might bedeaf. In children with autism, social and commu-nication skills usually increase by school age;however, problems dealing with change andtransitions and various self-stimulatory behaviors(sometimes including self-injury) also may becomemore prominent during this time.6 In adolescence,a small number of individuals with autism makemarked developmental gains; another subgroupwill behaviorally deteriorate (e.g., tantrums, self-injury, or aggression). Children and adolescentswith autism have an increased risk for accidentaldeath (e.g., drowning).7 Predictors of ultimateoutcome include the presence of communicativespeech by 5 years of age and overall cognitiveability (IQ). Evidence that earlier detectionand provision of services improves long-termprognosis makes early diagnosis particularlyimportant.8

The DSM-IV-TR category of pervasive devel-opmental disorders included autistic disorder,Rett’s disorder, Asperger’s disorder, childhooddisintegrative disorder, and pervasive develop-mental disorder not otherwise specified (PDD-NOS). Rett’s disorder was described by Andreas


238 www.jaacap.org VOLUME 53 NUMBER 2 FEBRUARY 2014


Rett in 1966 in a series of girls with unusual handwashing/wringing stereotyped mannerisms. Inmost cases, Rett’s disorder is caused by mutationsin the gene MeCP2 (methyl-CpG-binding protein2).9 Head circumference and development arenormal at birth and during infancy. Before 4 yearsof age, head growth decelerates, purposeful handmovements are lost, and characteristic stereo-typed hand movements (wringing or washing)develop.10 The central role ofMeCP2mutations inthis disorder makes it clear that boys may carrythe same mutations that lead to the full syndromein girls, but with differing clinical manifestationsranging from fatal encephalopathy11 to progres-sive but nonfatal developmental disorder12 tononspecific X-linked intellectual disability.13

Childhood disintegrative disorder (CDD) wasfirst described by Theodor Heller in 1908.14 Thiscondition is characterized by a period of at least 2years of normal development, followed by amarked deterioration and clinically significant lossof at least 2 skills in the areas of receptive orexpressive language, social skills, toileting skills,play, or motor skills.14 The onset of CDD is highlydistinctive, typically occurring at 3 to 4 years ofage and can be gradual or abrupt. Sometimesparents report that the child experienced a periodof anxiety or dysphoria before onset of CDDsymptoms. Once established, CDD resemblesautism in clinical features,14 but the outcome ispoor. The child typically becomes mute or, at best,regains limited speech.

Asperger’s disorder was described in 1944 butnot officially recognized until DSM-IV. Unlikechildren with autism, individuals with Asper-ger’s disorder do not present with delays in lan-guage acquisition or with unusual behaviors andenvironmental responsiveness during the firstyears of life. Consequently, parents often have noconcerns about their child’s early development.15

Asperger originally described children who wereprecocious in learning to talk but who then talkedin a formal, pedantic, 1-sided way, often about atopic of circumscribed interest.16 Social diffi-culties arise due to this idiosyncratic, 1-sided so-cial style. The outcome in Asperger’s disordergenerally appears to be better than that forautism, although this may, in part, relate tobetter cognitive and/or verbal abilities.8,15

The term pervasive developmental disordernot otherwise specified (PPD NOS) (also some-times termed atypical PDD or atypical autism)encompasses subthreshold cases on the autismspectrum, e.g., cases in which full criteria for one

of the explicitly defined PDDs are not met, butthe child has problems in social interaction andsome difficulties in communication or restrictedpatterns of behavior. Although studies arelimited, individuals with PDD-NOS typicallyhave been characterized as less impaired, havingfewer repetitive behaviors, and having a betterprognosis than persons with autism.16

DSM-IV-TR to DSM-5Because there was little evidence to support reli-able and replicable diagnostic differences amongthe various DSM-IV-TR PDDs,17 the DSM-5workgroup on neurodevelopmental disorderssubsumed the prior categories under the newdiagnosis of autism spectrum disorder (ASD) inthe DSM-5. Diagnostic domains were reducedfrom 3 to 2, focusing on social communicationand interaction deficits and restricted, repetitivepatterns of behaviors and interests. The strictrequirement for onset before 3 years of age waschanged to onset in the early developmentalperiod, the occurrence of potential sensory ab-normalities was incorporated, and a severity scalefor impairments in each of the 2 core domainswas included. Diagnostic reporting now includesspecifiers that may enhance descriptive subtyp-ing of the population, including specifiers for thepresence or absence of intellectual impairment,language impairment, catatonia, and knownmedical, genetic, or environmental factors. Thenew criteria allow for a history of symptoms thatmay not be present currently, recognizing thatthrough intervention or normal developmentsome children with autism no longer presentsome symptoms later in life. It will be some yearsbefore the implications of these changes forautism prevalence and other facets of assessmentand treatment can be fully assessed.

EPIDEMIOLOGYMany studies, mostly conducted outside theUnited States, have examined the prevalence ofautism or, less commonly, ASD or PDDs.17 Of theapproximately 36 surveys of autism available,prevalence estimates for autistic disorder rangefrom 0.7 in 10,000 to 72.6 in 10,000.18 The vari-ability in estimates reflects different factors,including changes in definition. When the 18 sur-veys conducted since the introduction of theDSM-IV criteria are considered, estimates rangingfrom 10 in 10,000 to 16 in 10,000, with a medianprevalence of 13 in 10,000, are obtained.18 Themost recent study by the Centers for Disease




Control and Prevention estimated the prevalenceof ASD in the United States as 11.3 in 1,000.19

Contrary to popular perception, data from 7 sur-veys suggest that rates of Asperger’s disorder arein fact lower than for typical autism (2.6 in 10,000or one fifth as common as typical autism).18

Recent observations of higher rates of autismhave led to concern that the prevalence of this dis-order may be increasing. Various factors maycontribute to an apparent increase,20 such as dif-ferences in diagnostic criteria and diagnostic prac-tices, the age of children screened, and the locationof the study (see Fombonne18 for discussion).

Autism is approximately 4 times more com-mon in males than in females, but females withautism tend to have more severe intellectualdisability. Although the original report by Kan-ner2 suggested a predominance of autism in moreeducated families, subsequent work has notshown this. Current approaches to the diagnosisof ASD appear to work well internationally andcross-culturally,3 although cultural aspects of thecondition have not received much attention.21

Within the United States, there may be underdi-agnosis in some circumstances (e.g., in disad-vantaged inner-city children).22

ETIOLOGYNeurobiologyElectroencephalographic (EEG) abnormalities andseizure disorders are observed in as many as 20%to 25% of individualswith autism.23 The high ratesof epilepsy suggest a role for neurobiologic factorsin autism.13,24,25 The number of areas affectedby autism suggests that a diverse and widelydistributed set of neural systems must be affected.Although various theories have posited potentialloci for difficulties, definitive data are lacking.Postmortem studies have shown various abnor-malities, particularly within the limbic system.25

Functional magnetic resonance imaging proce-dures have identified difficulties in tasks in-volving social and affective judgments anddifferences in the processing of facial and non-facial stimuli.26 Structural magnetic resonanceimaging has shown an overall brain size increasein autism, and diffusion tensor imaging studieshave suggested aberrations in white matter tractdevelopment.27 One of the most frequently repli-cated neurochemical findings has been the eleva-tion of peripheral levels of the neurotransmitterserotonin. The significance of this finding remainsunclear. A role for dopamine is suggested given

the problems with overactivity and stereotypedmannerisms and the positive response of suchbehaviors to neuroleptic medications.28

During the past decade, much concern hasfocused on vaccines as a possible postnatalenvironmental cause for ASD, with the concernfocused on the possibility that the measles-mumps-rubella vaccine may cause autism orthat thimerosal (a mercury-containing preserva-tive now removed from all single-dose vaccines)might do so.29 The preponderance of availabledata has not supported either hypothesis (seeRutter30 for a review). However, a possible role ofthe immune system in some cases of autism hasnot been ruled out.31

Neuropsychological correlates of ASD includeimpairments in executive functioning (e.g., simulta-neously engaging in multiple tasks),32 weak centralcoherence (integrating information into meaningfulwholes),33 and deficits in theory-of-mind tasks(taking the perspective of another person).34

Familial Pattern and Genetic FactorsThe high recurrence risk for autism in siblingsand even higher concordance for autism inidentical twins has provided strong support forthe importance of genetic factors.30 Higher ratesof autism are consistently noted in siblings ofaffected children. Recurrence risk has typicallybeen cited at 2% to 10%, but a recent prospectivelongitudinal study has reported a rate of 18.7%when the broad autism spectrum is considered.35

Identified risk factors for ASD appear to includecloser spacing of pregnancies, advanced maternalor paternal age, and extremely premature birth(<26 weeks’ gestational age).36-38 In addition,high rates of learning/language problems andsocial disability and a possible increase in the riskfor mood and anxiety disorders has been noted infamily members.

It is now clear that multiple genes are involvedin autism.30,39 Over the past several years, studieshave supported a role for common (present in>5%of the general population) and rare genetic varia-tions contributing to autism.40 The rate of progressin gene discovery has been increasing rapidly overthe past several years and these results are alreadybeginning to influence clinical practice with regardto genetic testing, as noted below.41

DIFFERENTIAL DIAGNOSISASD must be differentiated from specific develop-mental disorders (including language disorders),




sensory impairments (especially deafness), reactiveattachment disorder, obsessive-compulsive dis-order, intellectual disability, anxiety disordersincluding selective mutism, childhood-onsetschizophrenia, and other organic conditions.

A diagnosis of autism is made when therequisite DSM-5 symptoms are present and otherdisorders have been adequately ruled out. Inautism it is typical for parents to report thatthere was no period of normal development orthat there was a history of unusual behaviors(e.g., the child seemed too good and undemand-ing as an infant). Less commonly, a period ofapparently normal development is reported beforea regression (loss of skills). The topic of regressionin autism remains an active area of current inves-tigation. Developmental regression is typical inRett syndrome but also can be observed inother conditions (e.g., childhood-onset schizo-phrenia or degenerative CNS disorders).

Developmental language disorders have animpact on socialization and may be mistaken foran ASD. The distinction is particularly difficult inpreschool children. However, 2 behaviors havebeen reported to consistently differentiate autisticchildren from language-impaired peers at 20 and42 months of age, namely pointing for interestand use of conventional gestures.42 Similarly,differentiating mild to moderate developmentaldelay from ASD may be difficult, particularlywhen evaluating the younger child (see Chawarskaand Volkmar42 for a detailed discussion). Onestudy identified some items on the Autism Diag-nostic Interview that differentiated between these2 groups at 24 months, especially directing atten-tion (showing) and attention to voice (Table 1).43-56

At 36 months, 4 items correctly classified allsubjects: use of other’s body, attention to voice,pointing, and finger mannerisms. From 38 to 61months, children with autism were more likelyto show impaired nonverbal behaviors (such aseye contact) to regulate social interaction. Inchildhood, there may be diagnostic overlap be-tween ASD and attention-deficit/hyperactivitydisorder, making the differential diagnosisdifficult.57,58

Children with reactive attachment disordermay exhibit deficits in attachment and thereforeinappropriate social responsivity, but these usu-ally improve substantially if adequate caretakingis provided. Obsessive-compulsive disorder has alater onset than ASD, is not typically associatedwith social and communicative impairments, andis characterized by repetitive patterns of behavior

that are ego dystonic. Symptoms that characterizeanxiety disorders, such as excessive worry, theneed for reassurance, the inability to relax, andfeelings of self-consciousness, are also seen inASD, particularly in higher functioning in-dividuals. However, the 2 conditions can bedifferentiated by the prominent social andcommunicative impairments seen in ASD but notanxiety disorders, and the developed social insightof children with anxiety disorders, which is notseen in ASD. Differentiating childhood schizo-phrenia from autism can be difficult, because theyare characterized by social impairments and oddpatterns of thinking. However, florid delusionsand hallucinations are rarely seen in autism.

COMORBIDITIESGiven difficulties in communication (e.g., mutism)and cognitive impairment, issues of comorbidityin ASD can be quite complex. The process ofdiagnostic overshadowing (the tendency to failto diagnose other comorbid conditions whena more noticeable condition is present) mayoccur.59 Attempts to determine comorbidityprevalence in ASD have been hampered bymethodologic issues, although most studies haveshown increased rates of anxiety and attentionaldisorders.60

In most epidemiologically based samples ofpersons with autistic disorder, approximately50% exhibit severe or profound intellectualdisability, 35% exhibit mild to moderate intellec-tual disability, and the remaining 20% haveIQs in the normal range.18 For children withautistic disorder, verbal skills are typically moreimpaired than nonverbal skills. For children withAsperger’s disorder, the reverse pattern is some-times observed and the profile of nonverballearning disability may be present.61 Clearly, in-tellectual impairment is not an essential diag-nostic feature of autism, and thus it is necessaryand important for the diagnosis of intellectualdisability to be made.

A range of behavioral difficulties can beobserved in ASD, including hyperactivity,obsessive-compulsive phenomena, self-injury,aggression, stereotypies, tics, and affectivesymptoms. The issue of whether these qualify asadditional disorders is complex.3 Affectivesymptoms are frequently observed and includelability, inappropriate affective responses, anxi-ety, and depression. Impairments in emotionregulation processes can lead to under- and




TABLE1

Summaryof

Selected

Assessm

entInstru

men

tsforAutism

Spectru

mDisorde

ra

Scale(see

lege

nd)

Uses

Age

Rang

eMetho

dof

Adm

inistratio

nPo

pulatio

nStud

ied

Scalecharacteris

tics

Reference

ABC

screen

ing

child

ren

parent

rated

AD

57ite

ms,

scale1-4

Krug

etal.,19

8043

CARS

screen

ing

child

ren

clinicianrated

AD

15ite

ms,

scale1-4

Scho

pler

etal.,19

8044

M-CHAT

screen

ing

todd

lers

parent

rated

AD

23ite

ms,

yes/no

Robins

etal.,20

0145

CSB

S-DP-IT-Che

cklist

screen

ing

todd

lers

parent

rated

AD

24ite

ms

Wethe

rbyet

al.,20

0846

ASQ

screen

ing

child

/adu

ltpa

rent

rated

AD/A

spD

40ite

ms,

yes/no

Berumen

teta

l.,19

9947

AQ

screen

ing

child

/adu

ltselfor

parent

rated

AspD

50ite

ms,

scale0-3

Baron-Coh

enet

al.,20

0148

CAST

screen

ing

4-11

years

parent

rated

AspD

37ite

ms,

yes/no

Scotte

tal.,

2002

49

ASD

Sscreen

ing

5-18

years

parent

orteac

herrated

AspD

50ite

ms,

yes/no

Myles

etal.,20

0050

GADS

screen

ing

3-22

years

parent

orteac

herrated

AspD

32ite

ms,

scale0-3

Gilliam,2

0015

1

ASD

Iscreen

ing

child

/adu

ltinterview

þclinicianrated

AspD

50ite

ms,

yes/no

Gillbe

rget

al.,20

0152

SRS

screen

ing

4-18

years

parent

orteac

herrated

AspD

65ite

ms,

scale1-4

Con

stantinoet

al.,20

0353

ADI

diag

nostic

child

/adu

ltinterview

þclinicianrated

AD/A

spD

seetext

Lord

etal.,20

0354

DISCO

diag

nostic

child

/adu

ltinterview

þclinicianrated

AD/A

spD

seetext

Winget

al.,20

0255

ADOS

diag

nostic

child

/adu

ltsemi-stru

ctured

interactivesession

AD/A

spD

seetext

Lord

etal.,19

9456

Note:

ABC

¼Autism

Beha

vior

Checklist;AD

¼au

tism

disorder;ADI¼

Autism

Diagn

ostic

IntervieweRevised;

ADOS¼

Autism

Diagn

ostic

ObservationSc

hedu

le;AQ

¼Autism

Quo

tient;ASD

I¼Asperge

rSynd

rome

Diagn

ostic

Interview;ASD

S¼

Asperge

rSynd

romeDiagn

ostic

Scale;

AspD

¼Asperge

r’sdisorder;ASQ

¼Autism

ScreeningQuestion

naire

;CARS

¼Childho

odAutism

RatingSc

ale;

CAST

¼Childho

odAutism

ScreeningTest;

M-CHAT

¼Checklistfor

Autism

inTodd

lers;C

SBS-DP-IT-Checklist¼

Com

municationan

dSymbo

licBe

havior

Scales

Develop

mentalProfileInfant-To

ddlerC

hecklist;DISCO

¼Diagn

ostic

InterviewforS

ocial

andCom

municationDiso

rders;

GADS¼

Gilliam

Asperge

r’sDiso

rder

Scale;

Parent

¼primaryca

regiver;SR

S¼

Social

Respon

sivenessSc

ales.

aNotethat

theseinstrum

entsmay

need

tobe

revisedto

provideevidence

ofvalidity

forDS

M-5

ASD

andsupp

lementb

utDO

NOTREPLACEclinical

diag

nosis.




over-reactivity.62 Overt clinical depression is some-times observed and this may be particularly truefor adolescents with Asperger’s disorder.15 Casereports and case series have suggested possibleassociations with bipolar disorders and tics andTourette’s syndrome. Bullying involvement,including victimization and perpetration, occursmore frequently in general educational settings.63

Attentional difficulties also are frequent inautism, reflecting cognitive, language, and socialproblems.64 The historical prohibition on makingan additional diagnosis of attention-deficit/hyperactivity disorder in those with ASD hasbeen removed in the DSM-5. Notably, a subset ofchildren with ASD with elevated scores for hy-peractivity showed a 49% response rate in a largerandomized controlled trial of methylphenidatetreatment.64

EVIDENCE BASE FOR PRACTICEPARAMETERSIn this Parameter, recommendations for bestassessment and treatment practices are stated inaccordance with the strength of the underlyingempirical and/or clinical support.

$ Clinical standard [CS] is applied to recom-mendations that are based on rigorous empir-ical evidence (e.g., meta-analyses, systematicreviews, individual randomized controlled tri-als) and/or overwhelming clinical consensus.

$ Clinical guideline [CG] is applied to recom-mendations that are based on strong empiricalevidence (e.g., nonrandomized controlled trials,cohort studies, case-control studies) and/orstrong clinical consensus.

$ Clinical option [OP] is applied to recommen-dations that are based on emerging empiricalevidence (e.g., uncontrolled trials or case se-ries/reports) or clinical opinion but lack strongempirical evidence and/or strong clinicalconsensus.

$ Not endorsed [NE] is applied to practices thatare known to be ineffective or contraindicated.

The strength of the empirical evidence is ratedin descending order as follows:

$ [rct] Randomized controlled trial is applied tostudies in which subjects are randomlyassigned to at least 2 treatment conditions.

$ [ct] Controlled trial is applied to studies inwhich subjects are nonrandomly assigned to atleast 2 treatment conditions.

$ [ut] Uncontrolled trial is applied to studies inwhich subjects are assigned to 1 treatmentcondition.

$ [cs] Case series/report is applied to a caseseries or a case report.

ASSESSMENTRecommendation 1. The developmental assess-ment of young children and the psychiatricassessmentofall childrenshould routinely includequestions about ASD symptomatology [CS].

Screening should include inquiries about thecore symptomsofASD, including social relatednessand repetitive or unusual behaviors. Screeninginstruments have been developed that may behelpful to the clinician. Some of these instrumentsare completed by clinicians and others by primarycaregivers (Table 1).43-56 Screening is applicableto young children and to infants, when the diag-nosis may first be considered. In some instances,screening may be relevant to older children,e.g., those who are more intellectually able andwhose social disability is therefore more likely tobe detected later.

Recommendation 2. If the screening indicatessignificant ASD symptomatology, a thoroughdiagnostic evaluation should be performed todetermine the presence of ASD [CS].

Currently, biological diagnostic markers arenot available and diagnosis rests on carefulexamination of the child. A standard psychiat-ric assessment should be followed,65 includinginterviews with the child and family and a re-view of past records and historical information.The history and examination should be con-ducted with careful consideration of DSM-5diagnostic criteria. Although the DSM-5 criteriaare intended to be independent of age andintellect, the diagnosis of autism in infants andvery young children is more challenging, andsome features (e.g., stereotyped movements)may develop later.5 Systematic attention tothe areas relevant to differential diagnosisis essential. Information on the nature of changesover the course of development, e.g., in re-sponse to intervention, is helpful. The historyshould include a review of past and currenteducational and behavioral interventions andinformation regarding family history and rele-vant psychosocial issues. Consideration ofpossible comorbid diagnoses is an importantfocus of assessment.




Observation of the child should focus onbroad areas of social interaction and restricted,repetitive behaviors. The child’s age and devel-opmental level may dictate some modification inassessment procedures. Clinicians should besensitive to ethnic, cultural, or socioeconomicfactors that may affect assessment.

Various instruments for the assessment of ASDhave been developed (Table 143-56, see Coonrodand Stone66 for a review). As a practical matter,all these instruments vary in their usefulness forusual clinical practice. Some require specifictraining. The use of such instruments supple-ments, but does not replace, informed clinicaljudgment.3

Recommendation 3. Clinicians should coordi-nate an appropriate multidisciplinary assess-ment of children with ASD [CS].

All children with ASD should have a medicalassessment, which typically includes physical ex-amination, a hearing screen, a Wood’s lamp ex-amination for signs of tuberous sclerosis, andgenetic testing, which may include G-bandedkaryotype, fragile X testing, or chromosomalmicroarray. In a community sample of childrenwith ASD, diagnostic yields were 2.5% for karyo-type testing, 0.57% for fragile X testing, and 24%for chromosomal microarray.67 Chromosomalmicroarray has been recommended by medicalgeneticists as the standard of care for the initialevaluation of children with developmental dis-abilities and/or ASDs.68 These tests currentlydetect known abnormalities clearly associatedwith increased rates of ASD (e.g., 15q11-13maternal duplications and duplications and de-letions of chromosome 16p11.2) and genetic vari-ations of uncertain significance. Recent data from astudy of families with only a single affected childhave shown that lower IQ is not a strong predictorof a positive chromosomal finding.69 Anyabnormal or indeterminate result from such astudy warrants referral for further genetic evalu-ation and counseling. The yield of genetic testingin the presence of clinical suspicion is currently inthe range of at least one third of cases.70

Unusual features in the child (e.g., history ofregression, dysmorphology, staring spells, familyhistory) should prompt additional evaluations.The list of potential organic etiologies is large butfalls into the categories of infectious (e.g.,encephalitis or meningitis), endocrinologic (e.g.,hypothyroidism), metabolic (e.g., homocystinuria),traumatic (e.g., head injury), toxic (e.g., fetal

alcohol syndrome),4 or genetic (e.g., chromosomalabnormality). Certain developmental disorders,most notably Landau-Kleffner syndrome, alsoshould be ruled out. In this condition, a highlydistinctive EEG abnormality is present and asso-ciated with development of a marked aphasia.71

Genetic or neurologic consultation, neuroimaging,EEG, and additional laboratory tests should beobtained when relevant, based on examination orhistory (e.g., testing for theMeCP2 gene in cases ofpossible Rett’s disorder).72

Psychological assessment, including measure-ments of cognitive ability and adaptive skills, isindicated for treatment planning and helps toframe observed social-communication difficultiesrelative to overall development. The results ofstandard tests of intelligence may show consid-erable scatter. Unusual islets of ability (“splinterskills”) may be present. For children with autism,these sometimes take the form of unusual ability(“savant skills”), e.g., the ability to produceintricate drawings or engage in calendar calcula-tions. For higher functioning children, areas ofspecial interest are often present and the single-minded pursuit of these interests may interferewith the child’s ability to learn. Psychologicaltests clarify areas of strength and weaknessuseful in designing intervention programs andmay need to include instruments valid for anonverbal population.7

Communication assessment, including mea-surements of receptive and expressive vocabularyand language use (particularly social or prag-matic), is helpful for diagnosis and treatmentplanning.73 Occupational and physical therapyevaluations may be needed to evaluate sensoryand/or motor difficulties.74 Sleep is an importantvariable to assess in individuals with ASD.75

When members of multiple disciplines are in-volved in assessment, it is optimal that coordina-tion occur among the various professionals.

TREATMENTRecommendation 4. The clinician should helpthe family obtain appropriate, evidence-based,and structured educational and behavioral in-terventions for children with ASD [CS].

Structured educational and behavioral in-terventions have been shown to be effective formany children with ASD76 and are associatedwith better outcome.8 As summarized in theNational Research Council report,76 the qualityof the research literature in this area is variable,




with most studies using group controls or single-subject experimental methods. In general, stud-ies using more rigorous randomized group com-parisons are sparse, reflecting difficulties inrandom assignment and control comparisons.Other problems include lack of attention to sub-ject characterization, generalization of treatmenteffects, and fidelity of treatment implementation.Despite these problems, various comprehensivetreatments approaches have been shown to haveefficacy for groups of children, although none ofthe comprehensive treatment models has clearlyemerged as superior.76

BehavioralBehavioral interventions such as Applied Behav-ioral Analysis (ABA) are informed by basic andempirically supported learning principles.77 Awidely disseminated comprehensive ABA pro-gram is Early Intensive Behavioral Interventionfor young children, based on the work of Lovaaset al.78 Early Intensive Behavioral Intervention isintensive and highly individualized, with up to40 hours per week of one-to-one direct teaching,initially using discrete trials to teach simple skillsand progressing to more complex skills such asinitiating verbal behavior. A meta-analysis foundEarly Intensive Behavioral Intervention effectivefor young children but stressed the need formore rigorous research to extend the findings.79

Behavioral techniques are particularly usefulwhen maladaptive behaviors interfere with theprovision of a comprehensive intervention pro-gram. In such situations, a functional analysis ofthe target behavior is performed, in which pat-terns of reinforcement are identified and thenvarious behavioral techniques are used to pro-mote a desired behavioral alternative. ABAtechniques have been repeatedly shown to haveefficacy for specific problem behaviors,80 andABA has been found to be effective as applied toacademic tasks,81[ut] adaptive living skills,82[ut]

communication,83[ut] social skills,84[ut] and voca-tional skills.85[ct] Because most children with ASDtend to learn tasks in isolation, an explicit focuson generalization is important.86

CommunicationCommunication is a major focus of interventionand typically will be addressed in the child’sindividualized educational plan in coordinationwith the speech-language pathologist. Childrenwho do not yet use words can be helped throughthe use of alternative communication modalities,

such as sign language, communication boards,visual supports, picture exchange, and otherforms of augmentative communication. There issome evidence for the efficacy of the PictureExchange Communication System, sign language,activity schedules, and voice output communica-tion aids.87[rct],88-90 For individuals with fluentspeech, the focus should be on pragmatic languageskills training. Children and adolescents withfluent speech may, for example, be highly verbalbut have severely impaired pragmatic languageskills that can be addressed through explicitteaching. Many programs to enhance socialreciprocity and pragmatic language skills arecurrently available (Table 2; see Reichow andVolkmar91 for an extensive review).92-103

EducationalThere is consensus that children with ASD need astructured educational approach with explicitteaching.76 Programs shown to be effective typi-cally involve planned, intensive, individualizedintervention with an experienced, interdisci-plinary team of providers, and family involve-ment to ensure generalization of skills. Theeducational plan should reflect an accurateassessment of the child’s strengths and vulnera-bilities, with an explicit description of services tobe provided, goals and objectives, and pro-cedures for monitoring effectiveness. Althoughthe curricula used vary across programs, theyoften share goals of enhancing verbal andnonverbal communication, academic skills, andsocial, motor, and behavioral capabilities. Insome instances, particularly for younger children,a parent-education and home component may beimportant. Development of an appropriate indi-vidualized educational plan is central inproviding effective service to the child and fam-ily. Efficacy has been shown for 2 of the struc-tured educational models, the Early Start DenverModel104[rct] and the Treatment and Education ofAutism and related Communication handi-capped Children program,105[ct] but significantchallenges remain in disseminating knowledgeabout effective interventions to educators.

Other InterventionsThere is a lack of evidence for most other formsof psychosocial intervention, although cognitivebehavioral therapy has shown efficacy for anxietyand anger management in high functioning youthwith ASD.106[rct],107[rct] Studies of sensory ori-ented interventions, such as auditory integration




training, sensory integration therapy, and touchtherapy/massage, have contained methodo-logic flaws and have yet to show replicableimprovements.108,109 There is also limited evi-dence thus far for what are usually termeddevelopmental, social-pragmatic models of in-tervention, such as Developmental-IndividualDifference-Relationship Based/Floortime, Re-lationship Development Intervention, Social

Communication Emotional Regulation andTransactional Support, and Play and Languagefor Autistic Youths, which generally use natu-ralistic techniques in the child’s communitysetting to develop social communication abili-ties. Children with ASD are psychiatricallyhospitalized at substantially higher rates thanthe non-ASD child population.110 The efficacyof this intervention is unknown, although there

TABLE 2 Methods Available for the Delivery of Social Reciprocity/Pragmatic Language-Oriented Interventions

DevelopmentalLevel Method Notes Reference

Infant/preschool(play based)

guided participation adult coaching and mediation bytrained peers

Schuler and Wolfberg,200292

Do-Watch-Listen-Say careful selection of play materials tofoster participation; organizationof environment to facilitateparticipation and cooperation

Quill, 200093

play organizers neurotypical peers taught toencourage sharing, helping, andpraising to facilitate play; someevidence of generalization

Strain et al., 197794

buddy skills teaches neurotypical peers to staywith, play with, and talk to their“buddies”; some evidence ofimprovement in the frequency ofsocial communication that wasgeneralized to other interactions

Goldstein and Wikstrom,199695

School age social stories state a problem and give the childan acceptable response to it;usually focuses on maladaptivebehaviors; little evidence ofgeneralization and maintenance

Gray, 200096

social skills groups see text Kamps et al., 199797

peer network/circle offriends

typical peers taught to initiate andmodel appropriate socialinteractions; results have shownimprovement in interaction andgeneralization to new settings

Kamps et al., 199797;Whitaker et al., 199898

Adolescence peer network/circle offriends

see above Whitaker et al., 199898;Paul, 200399

visual schedule/verbalrehearsal

using written and pictorialrepresentations of expectedactivities and behavior

Klin and Volkmar, 2000100;Hodgdon, 1995101

social skills group see text Paul, 200399

social thinking addresses underlying socialcognitive knowledge required forexpression of related social skills;promotes teaching the “why”behind socialization

Crooke et al., 2007102

training scripts scripts are provided that give theopportunity to ask questions inresponse to others ¼ initiation ofconversation

Klin and Volkmar, 2000103




TABLE3

Rand

omized

Con

trolledTrialsof

Psycho

tropicMed

ications

inChildrenan

dAdo

lescen

tsW

ithAutism

Spectru

mDisorde

r(ASD

)

Age

ntStud

yTa

rget

Symptom

sDo

seDe

mog

raph

ics

Sign

ificant

Side

Effects

Prim

aryOutcome(s)

a 2Ago

nists

Clonidine

Jaselsk

iset

al.,

1992

116

hype

ractivity,irritability,

inap

prop

riate

spee

ch,

stereotyp

y

0.15

-0.20mg

divide

d3%

/d8child

ren5-13

yold

hypo

tension,

drow

siness

statistically

andclinically

releva

ntde

crea

sein

ABC

Irrita

bilitysubsca

leGua

nfac

ine

Han

denet

al.,

2008

117

hype

ractivity,ina

ttention

1-3mgdivide

d3%

/d7child

renwith

ASD

5-9yold

drow

siness,

irrita

bility

45%

with

>50

%de

crea

sein

ABC

Hyp

erac

tivity

subsca

leAntipsychotics

Arip

iprazo

leb M

arcuset

al.,

2009

118

irrita

bility,

hype

ractivity,

stereotyp

y,social

with

draw

al,ina

ppropriate

spee

ch

5,10

,or1

5mg/

dfixeddo

se21

8child

ren6-17

yold

somno

lence,

weigh

tga

in,d

rooling,

tremor,

fatig

ue,v

omiting

56%

positiverespon

seafor

aripiprazo

le5mgvs.3

5%on

plac

ebo;

significa

ntim

prov

emen

tinIrrita

bility,

Hyp

erac

tivity,a

ndStereo

typy

subsca

les

b Owen

etal.,

2009

119

irrita

bility,

hype

ractivity,

stereotyp

y,social

with

draw

alinap

prop

riate

spee

ch

5-15

mg/

dflexibly

dosed

98child

ren6-17

yold

somno

lence,

weigh

tga

in,d

rooling,

tremor,

fatig

ue,v

omiting

52%

positiverespon

seafor

aripiprazo

levs.1

4%on

plac

ebo;

significa

ntim

prov

emen

tinIrrita

bility,

Hyp

erac

tivity,a

ndStereo

typy

subsca

les

Halop

eridol

And

ersonet

al.,

1984

120

multip

lebe

havioral

symptom

s,glob

alfunctio

ning

0.5-4mg/

d40

child

ren2-7yold

seda

tion,

irrita

bility,

extra

pyramidal

symptom

s(>

25%)

beha

vioral

symptom

sim

prov

edwith

significa

ntde

crea

sein

8of

14ite

ms

ofCPR

SAnd

ersonet

al.,

1989

121

multip

lebe

havioral

symptom

s,glob

alfunctio

ning

0.25

-4mg/

d45

child

ren2-7yold

seda

tion,

extra

pyramidal

symptom

s

beha

vioral

symptom

sim

prov

edwith

significa

ntde

crea

sein

7of

14ite

ms

ofCPR

SOlanz

apine

b Holland

eret

al.,

2006

122

glob

alfunctio

ning

,ag

gressio

n,co

mpu

lsion

s,irrita

bility

7.5-12

.5mg/

d11

child

ren6-14

yold

weigh

tgain,

seda

tion

50%

ofthoseon

olan

zapine

muchor

very

much

improv

edin

glob

alfunctio

ning

vs.2

0%on

plac

ebo

Risperidon

eRU

PP,2

0021

23

irrita

bility,

hype

ractivity,

stereotyp

y,social

with

draw

al,ina

ppropriate

spee

ch

0.5-3.5mg/

d10

1child

ren5-17

yold

weigh

tgain,

increa

sed

appe

tite,

fatig

ue,

drow

siness,

droo

ling,

dizz

iness

69%

hadpo

sitiverespon

sea

onrispe

ridon

evs.1

2%po

sitiverespon

seaon

plac

ebo;

significa

ntpo

sitive

find

ings

forh

yperac

tivity

andste

reotyp

y




TABLE3

Con

tinued

Age

ntStud

yTa

rget

Symptom

sDo

seDe

mog

raph

ics

Sign

ificant

Side

Effects

Prim

aryOutcome(s)

b She

aet

al.,

2004

124

irrita

bility,

hype

ractivity,

stereotyp

y,social

with

draw

al,ina

ppropriate

spee

ch

0.02

-0.06mg/

kg/d

79child

ren5-12

yold

weigh

tgain,

somno

lence,

64%

improv

emen

tinABC

Irrita

bilitysubsca

leon

rispe

ridon

evs.3

1%im

prov

emen

tonplac

ebo;

significa

ntpo

sitivefind

ing

forh

yperac

tivity

McD

ougleet

al.,

2005

125

social

andco

mmun

ication

impa

irmen

t,repe

titive

beha

vior

andste

reotyp

y

0.5-3.5mg/

d10

1child

ren5-17

yold

weigh

tgain,

increa

sed

appe

tite,

fatig

ue,

drow

siness,

droo

ling,

dizz

iness

significa

ntrespon

secfor

repe

titivebe

havior

and

stereotyp

yon

rispe

ridon

e

Risperidon

evs.

halope

ridol

b Mira

leta

l.,20

08126

beha

vior,s

ocial,sensory,

lang

uage

0.01

-0.08mg/

kg/d

30child

ren8-18

yold

EPS,

weigh

tgain,

gyne

comastia

rispe

ridon

erepo

rtedsupe

rior

toha

lope

ridol

only

onABC

totalsco

re,n

osubsca

les

repo

rted

Moo

dsta

bilizers

Valproic

acid

Hellings

etal.,

2005

127

irrita

bility

20mg/

kg/d

,av

erag

elevel

75-78

30subjects6-20

yold

increa

sedap

petite,

skin

rash

nosig

nifica

ntdiffe

rencefor

ABC

Irrita

bilitysubsca

le

b Holland

eret

al.,

2005

128

repe

titivebe

havior

500-1,50

0mg/

d12

child

ren5-17

yold,

1ad

ult4

0yold

irrita

bility,

aggressio

nsta

tistically

significa

ntde

crea

sein

repe

titive

beha

vior

onCY-BO

CS

Holland

eret

al.,

2010

129

glob

alirrita

bility

dosedto

mea

nlevel

of89

.8mg

/mL

27child

ren5-17

yold

skin

rash,irritability

62.5%

positiverespon

sefor

irrita

bilityon

CGIo

ndiva

lproex

vs.9

.09%

onplac

ebo

Lamotrig

ine

b Belsitoet

al.,

2001

130

irrita

bility,

social

beha

vior

5mg/

kg/d

28child

ren3-11

yold

insomnia,

hype

ractivity

nosig

nifica

ntdiffe

rencein

irrita

bilityor

social

beha

vior

onmultip

leinstrum

ents

Levetirac

etam

b Wasserm

anet

al.,

2006

131

irrita

bility,

glob

alfunctio

ning

20-30mg/

kg/d

20child

ren5-17

yold

aggressio

nno

significa

ntdiffe

rencein

glob

alfunctio

ning

orirrita

bility

Norep

inep

hrine

reup

take

inhibitors

Atomox

etineHCI

b Harfte

rkam

pet

al.,

2012

132

hype

ractivity,ina

ttention

1.2mg/

kg/d

97child

ren6-17

yold

nausea

,ano

rexia,

fatig

ue,e

arly

wak

ening

significa

ntdiffe

rencein

the

ADHD-RS

fora

ctive

treatmen

tgroup

;no

diffe

rencein

CGI-I




TABLE3

Con

tinued

Age

ntStud

yTa

rget

Symptom

sDo

seDe

mog

raph

ics

Sign

ificant

Side

Effects

Prim

aryOutcome(s)

b Arnoldet

al.,

2006

133

hype

ractivity,ina

ttention

20-100

mgdivide

d2%

,mea

n44

mg/

d

16child

ren5-15

yold

uppe

rGIsym

ptom

s,fatig

ue,rac

inghe

art

57%

positiverespon

seafor

parent-ra

tedABC

Hyp

erac

tivity

subsca

levs.

25%

onplac

ebo

Serotoninreup

take

inhibitors

Cita

lopram

King

etal.,20

09134

repe

titivebe

havior

2.5-20

mg/

d,mea

n16

mg/

d14

9child

ren5-17

yold

hype

ractivity,insom

nia,

inattention,

impu

lsivity,

diarrhea

,stereotyp

y

nosig

nifica

ntdiffe

rencein

repe

titivebe

havior

onCGI-I

andCY-BO

CSPD

DFluo

xetin

eHolland

eret

al.,

2005

135

repe

titivebe

havior

2.4-20

mg/

d,mea

n9.9mg/

d39

child

ren5-17

yold

none

significa

ntsta

tistically

significa

ntde

crea

sein

repe

titive

beha

vior

onCY-BO

CS

Com

pulsion

sscale

Clomipramine

Gordo

net

al.,

1993

136

stereotyp

y,repe

titive

beha

vior,c

ompu

lsion

s25

-250

mg/

d,mea

n15

2mg/

d12

child

ren6-18

yold

insomnia,

constip

ation,

twitching

,tremors

decrea

sein

repe

titive

beha

vior

onCPR

SRe

mington

etal.,

2001

137

stereotyp

y,irrita

bility,

hype

ractivity

100-15

0mg/

d,mea

n12

8.4mg/

d31

subjects<20

yold

lethargy

,tremors,

tachycardia,

insomnia,

diap

horesis

,nau

sea

nosig

nifica

ntdiffe

rencein

stereotyp

y,irrita

bility,

orhy

peractivity

for

clom

ipramineon

ABC

Stim

ulan

tsMethy

lphe

nida

teRU

PP,2

0051

38

hype

ractivity

7.5-50

mg/

ddivide

d3%

/d58

child

ren5-14

yold

decrea

sedap

petite,

insomnia,

irrita

bility,

emotiona

lity

49%

positiverespon

dersafor

hype

ractivity

vs.1

5.5%

onplac

ebo

Pearsonet

al.,

2013

139

hype

ractivity,ina

ttention

10-40mg

each

morning

,methy

lphe

nida

teextend

edrelease

24child

ren7-12

yold

decrea

sedap

petite,

insomnia

significa

ntde

crea

sein

hype

ractivity

andinattention

onmultip

leteac

hera

ndpa

rent

mea

suremen

tsHan

denet

al.,

2000

140

hype

ractivity

0.3-0.6mg/

kg/

dose,2

-3%/d

13child

ren5-11

yold

social

with

draw

al,

irrita

bility

8of

13child

renwith

>50

%de

crea

sein

hype

ractivity

onTeac

herC

onne

rsHyp

erac

tivity

subsca

leQuintan

aet

al.,

1995

141

hype

ractivity

10-20mg2%

/d10

child

ren7-11

yold

irrita

bility,

anorexia,

insomnia

decrea

sein

ABC

Hyp

erac

tivity

subsca

leby

8po

intsov

erplac

ebo

Misc

ellane

ous

Aman

tadine

b Kinget

al.,

2001

142

hype

ractivity,irritability

2.5-5.0mg/

kg/d

39child

ren5-19

yold

insomnia

nosta

tistical

diffe

rencein

parent

ABC

Hyp

erac

tivity

orIrrita

bilitysubsca

les,

statistical

improv

emen

tin

clinicianHyp

erac

tivity

and

Inap

prop

riate

Spee

chsubsca

les




TABLE3

Con

tinued

Age

ntStud

yTa

rget

Symptom

sDo

seDe

mog

raph

ics

Sign

ificant

Side

Effects

Prim

aryOutcome(s)

Cyp

rohe

ptad

ine

(inco

mbina

tion

with

halope

ridol)

Akhon

dzad

ehet

al.,

2004

143

ABC

totalsco

re,C

ARS

Titra

tedup

to0.2

mg/

kg/d

40child

ren3-11

yold

none

significa

nt,trend

towardincrea

sed

appe

tite

statistically

significa

ntdiffe

rencein

ABC

totalsco

rean

dCARS

diag

nostic

screen

ingtool,w

ithun

know

nclinical

significa

nce

Don

epez

ilChe

zet

al.,20

03144

“autistic

beha

vior,”

expressiv

e-receptive

commun

ication

1.25

-2.5

mg/

d43

child

ren2-10

yold

diarrhea

,stomac

hcram

ping

,irritability

“autistic

beha

vior”

statistically,improv

edon

CARS

diag

nosticscreen

ing

tool

with

unknow

nclinical

significa

nce

Naltre

xone

Willem

sen-Sw

inkels

etal.,19

95145

“soc

ialb

ehav

ior,”

irrita

bility

single40

-mgdo

se20

child

ren3-7yold

seda

tion,

increa

sed

stereotyp

yno

effect

onsocial

beha

vior;

significa

ntde

crea

seon

ABC

Irrita

bilitysubsca

levs.

plac

ebo

b Kolmen

etal.,

1995

146

hype

ractivity,

commun

icationinitiation

1mg/

kg/d

13child

ren3-8yold

transient

seda

tion

nosig

nifica

ntdiffe

rencein

commun

icationinitiation

b Feldm

anet

al.,

1999

147

commun

ication

1mg/

kg/d

24child

ren,

3-8yold

transient

seda

tion

nosig

nifica

ntdiffe

rencein

multip

leco

mmun

ication

mea

suremen

tsCam

pbelle

tal.,

1993

148

CGI,CPR

S,discrim

inan

tlearning

,hyp

erac

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is preliminary evidence for the efficacy ofhospital psychiatry units that specialize in thepopulation.111

Recommendation 5. Pharmacotherapy may beoffered to children with ASD when there is aspecific target symptom or comorbid condi-tion [CG].

Pharmacologic interventions may increase theability of persons with ASD to profit fromeducational and other interventions and toremain in less restrictive environments throughthe management of severe and challengingbehaviors. Frequent targets for pharmacologicintervention include associated comorbid condi-tions (e.g., anxiety, depression) and other fea-tures, such as aggression, self-injurious behavior,hyperactivity, inattention, compulsive-like be-haviors, repetitive or stereotypic behaviors, andsleep disturbances. As with other children andadolescents, various considerations should informpharmacologic treatment.112 Risperidone113[rct]

and aripiprazole114[rct] have been approved by

the Food and Drug Administration for thetreatment of irritability, consisting primarilyof physical aggression and severe tantrumbehavior, associated with autism. There is agrowing body of controlled evidence for phar-macologic intervention,115 and a summary ofrandomized controlled trials of medication inchildren with ASD is included (Table 3).116-150

Combining medication with parent training ismoderately more efficacious than medicationalone for decreasing serious behavioral distur-bance and modestly more efficacious for adap-tive functioning.151[rct],152[rct] Individuals withASD may be nonverbal, so treatment response isoften judged by caregiver report and observa-tion of specific behaviors. Although this mayhelp document the effectiveness of the selectedmedication, one must remember that an overallgoal of treatment is to facilitate the child’sadjustment and engagement with educationalintervention. Several objective rating scalesalso are available to help monitor treatmentresponse.153

TABLE 4 Resources for Parents

ASPEN TM, Inc. (Asperger Syndrome EducationNetwork) (http://www.aspennj.org)

A regional nonprofit organization providing families and thoseindividuals affected with Asperger syndrome and relateddisorders with information, support, and advocacy.

Autism Society of America (http://www.autism-society.org)

The mission of the Autism Society of America is to promotelifelong access and opportunities for persons within the autismspectrum and their families to be fully included, participatingmembers of their communities through advocacy, publicawareness, education, and research related to autism.

Autism Speaks (http://www.autismspeaks.org) Autism Speaks is an autism science and advocacy organizationdedicated to funding research into the causes, prevention,treatments, and a cure for autism; increasing awareness ofautism spectrum disorders; and advocating for the needs ofindividuals with autism and their families.

Division TEACCH (Treatment and Education ofAutism and related Communication handicappedChildren, University of North Carolina at ChapelHill) (www.teacch.com)

The TEACCH Web site includes information about theirprogram, educational and communication approaches toteaching individuals with autism, their research and trainingopportunities, and information and resources on autism.

LDAA (Learning Disabilities Association of America)(http://www.ldanatl.org)

The LDAA site includes information and resources on manylearning disabilities, including learning disabilities involving asignificant social component, such as autism and Aspergersyndrome.

OASIS (Online Asperger Syndrome Information andSupport) (http://www.asperger.org)

General information on Asperger syndrome and relateddisorders, including resources and materials, announcementsof major pertinent events and publications, and being themajor “intersection” for communication among parents,clinicians, educators, and individuals with social disabilities.

Yale Child Study Center (www.autism.fm) Information on autism, Asperger syndrome, and relateddisorders, lists of resources organized by state, and parentsupport organizations and advocacy agencies.




Recommendation 6. The clinician shouldmaintain an active role in long-term treatmentplanning and family support and support of theindividual [CG].

Children’s and families’ need for help and sup-port will change over time. The clinician shoulddevelop a long-term collaboration with the familyand realize that service utilizationmaybe sporadic.For very young children, issues of diagnosis andidentification of treatment programs often will bemost important. For school-age children, psycho-pharmacologic and behavioral issues typicallybecome more prominent. For adolescents, voca-tional and prevocational training and thoughtfulplanning for independence/self-sufficiency isimportant. As part of this long-term engage-ment, parents and siblings of children with ASDwill need support (Table 4). Although raising achild with autism presents major challenges,rates of parental separation and divorce are nothigher among parents of children with ASD thanthose with non-ASD children.154

Recommendation 7. Clinicians should specif-ically inquire about the use of alternative/com-plementary treatments and be prepared todiscuss their risk and potential benefits [CS].

Although most alternative or complementarytreatment approaches have very limited empiricalsupport for their use in children with ASD, theyare commonly pursued by families.155 It isimportant that the clinician be able to discussthese treatments with parents, recognizing themotivation for parents to seek all possible treat-ments. In most instances, these treatments havelittle or no proved benefit but also have littlerisk.7 In a few instances, the treatment has beenrepeatedly shown not to work (e.g., intravenousinfusion of secretin156 and oral vitamin B6 andmagnesium157[rct]), or randomized controlledevidence does not support its use (e.g., the gluten-free, casein-free diet,158 u-3 fatty acids,159 andoral human immunoglobulin).160[rct] Some treat-ments have greater potential risk to the childdirectly (e.g., mortality and morbidity associatedwith chelation161[cs]) or from side effects owing tocontaminants in “natural” compounds or indi-rectly (e.g., by diverting financial or psychosocialresources). For a detailed review of alternativetreatments, see Jacobson et al.162 and Levy andHyman.163 Although more controlled studies ofthese treatments are needed, it is important thatthe family be able to voice their questions tohealth care providers. Families may be guided to

the growing body of work on evidence-basedtreatments in autism.164

PARAMETER LIMITATIONSAACAP Practice Parameters are developed toassist clinicians in psychiatric decision making.These Parameters are not intended to define thesole standard of care. As such, the Parametersshould not be deemed inclusive of all propermethods of care or exclusive of other methodsof care directed at obtaining thedesired results. Theultimate judgment regarding the care of a partic-ularpatientmust bemadeby the clinician in light ofall of the circumstances presented by the patientand his or her family, the diagnostic and treatmentoptions available, and available resources. &

This Parameter was developed by Fred Volkmar, MD, Matthew Siegel,MD, Marc Woodbury-Smith, MD, Bryan King, MD, JamesMcCracken, MD, Matthew State, MD, PhD, and the AmericanAcademy of Child and Adolescent Psychiatry (AACAP) Committee onQuality Issues (CQI): William Bernet, MD, Oscar G. Bukstein, MD,MPH, and Heather J. Walter, MD, MPH, co-chairs; and ChristopherBellonci, MD, R. Scott Benson, MD, Regina Bussing, MD, AllanChrisman, MD, Tiffany R. Farchione, MD, John Hamilton, MD, MunyaHayek, MD, Helene Keable, MD, Joan Kinlan, MD, Nicole Quiterio,MD, Carol Rockhill, MD, Ulrich Schoettle, MD, Matthew Siegel, MD,and Saundra Stock, MD.

The AACAP Practice Parameters are developed by the AACAP CQI inaccordance with American Medical Association policy. Parameterdevelopment is an iterative process between the primary author(s), theCQI, topic experts, and representatives from multiple constituentgroups, including the AACAP membership, relevant AACAP commit-tees, the AACAP Assembly of Regional Organizations, and the AACAPCouncil. Details of the Parameter development process can beaccessed on the AACAPWeb site. Responsibility for Parameter contentand review rests with the author(s), the CQI, the CQI ConsensusGroup, and the AACAP Council.

The AACAP develops patient-oriented and clinician-oriented PracticeParameters. Patient-oriented Parameters provide recommendations toguide clinicians toward best assessment and treatment practices.Recommendations are based on the critical appraisal of empiricalevidence (when available) and clinical consensus (when not) and aregraded according to the strength of the empirical and clinical support.Clinician-oriented Parameters provide clinicians with the information(stated as principles) needed to develop practice-based skills. Althoughempirical evidence may be available to support certain principles,principles are based primarily on clinical consensus. This Parameter isa patient-oriented Parameter.

The primary intended audience for the AACAP Practice Parametersis child and adolescent psychiatrists; however, the informationcontained therein also may be useful for other mental health clini-cians.

The authors acknowledge the following experts for their contributionsto this Parameter: Andr!es Martin, MD, Schuyler Henderson, MD,Rhea Paul, PhD, Joaquin Fuentes, MD, Christopher McDougle, MD,Ami Klin, PhD, and Connie Zajicek, MD.

Kristin Kroeger Ptakowski and Jennifer Medicus served as the AACAPstaff liaisons for the CQI.

This Practice Parameter was reviewed at the Member Forum at theAACAP annual meeting in October 2006.

From March to June 2012, this Parameter was reviewed by aconsensus group convened by the CQI. Consensus group members




and their constituent groups were Oscar G. Bukstein, MD, co-chair;R. Scott Benson, MD, and John Hamilton, MD (CQI); Doug Novins,MD, and Christopher Thomas, MD (topic experts); Bryan King, MD(AACAP Autism and Intellectual Disability Committee); Melissa Del-Bello, MD (AACAP Research Committee); John Rose, MD, and SyedNaqvi, MD (AACAP Assembly of Regional Organizations); andLouis Kraus, MD, and Tami Benton, MD (AACAP Council).

This Practice Parameter was approved by the AACAP Council on July8, 2013.

This Practice Parameter is available on the Internet (http://www.aacap.org).

Disclosures: Fred Volkmar, MD, receives or has received researchfunding from the National Institute of Child Health and HumanDevelopment and the National Institute of Mental Health and has in-tellectual property with JohnWiley & Sons, Inc., Guilford Publications,Inc, and Springer. Matthew Siegel, MD, has no financial conflicts ofinterest to disclose. Marc Woodbury-Smith, MD, has no financialconflicts of interest to disclose. Bryan King, MD, has or has receivedresearch funding from the National Institutes of Health (NIH), SeasideTherapeutics, and Health Resources and Services Administration and

serves or has served as an advisor/consultant with the U.S. Depart-ment of Justice. James McCracken, MD, has or has received researchfunding from Seaside Therapeutics and Bristol-Myers Squibb, serves orhas served as an advisor/consultant to BioMarin Pharmaceuticals,Inc., and receives or has received honoraria as a speaker for Veritas,Discovery Channel Health CME, and CME Outfitters, LLC. MatthewState, MD, has or has received research funding from the NIH andHoward Hughes Medical Institute and has an exclusive licenseagreement with Athena Diagnostics. Oscar Bukstein, MD, MPH, co-chair, has served as a consultant for Ezra Innovations and for PRIMECME. He receives royalties from Routledge Press. Heather Walter,MD, MPH, and William Bernet, MD, co-chairs, have no financial re-lationships to disclose. Disclosures of potential conflicts of interest forall other individuals named above are provided on the AACAP Website on the Practice Parameters page.

Correspondence to the AACAP Communications Department, 3615Wisconsin Avenue, NW, Washington, D.C. 20016.

0890-8567/$36.00/ª2014 American Academy of Child andAdolescent Psychiatry

http://dx.doi.org/10.1016/j.jaac.2013.10.013

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