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A Practice Pathway for the Identification, Evaluation, andManagement of Insomnia in Children and AdolescentsWith Autism Spectrum Disorders

abstractOBJECTIVE: This report describes the development of a practice path-way for the identification, evaluation, and management of insomnia inchildren and adolescents who have autism spectrum disorders (ASDs).

METHODS: The Sleep Committee of the Autism Treatment Network(ATN) developed a practice pathway, based on expert consensus, tocapture best practices for an overarching approach to insomnia bya general pediatrician, primary care provider, or autism medical spe-cialist, including identification, evaluation, and management. A fieldtest at 4 ATN sites was used to evaluate the pathway. In addition, a sys-tematic literature review and grading of evidence provided dataregarding treatments of insomnia in children who have neurodevelop-mental disabilities.

RESULTS: The literature review revealed that current treatments forinsomnia in children who have ASD show promise for behavioral/educational interventions and melatonin trials. However, there isa paucity of evidence, supporting the need for additional research.Consensus among the ATN sleep medicine committee expertsincluded: (1) all children who have ASD should be screened forinsomnia; (2) screening should be done for potential contributingfactors, including other medical problems; (3) the need fortherapeutic intervention should be determined; (4) therapeuticinterventions should begin with parent education in the use ofbehavioral approaches as a first-line approach; (5) pharmacologictherapy may be indicated in certain situations; and (6) there shouldbe follow-up after any intervention to evaluate effectiveness andtolerance of the therapy. Field testing of the practice pathway byautism medical specialists allowed for refinement of the practicepathway.

CONCLUSIONS: The insomnia practice pathway may help health careproviders to identify and manage insomnia symptoms in children andadolescents who have ASD. It may also provide a framework to evaluatethe impact of contributing factors on insomnia and to test the effec-tiveness of nonpharmacologic and pharmacologic treatment strategiesfor the nighttime symptoms and daytime functioning and quality of lifein ASD. Pediatrics 2012;130:S106–S124

AUTHORS: Beth A. Malow, MD, MS,a,b,c Kelly Byars, PsyD,d

Kyle Johnson, MD,e Shelly Weiss, MD,f Pilar Bernal, MD,a,c

Suzanne E. Goldman, PhD,g Rebecca Panzer, MA, RD, LD,h

Daniel L. Coury, MD,i and Dan G. Glaze, MDj

Departments of aNeurology and bPediatrics and cKennedy Center,Vanderbilt University Medical Center, Nashville, Tennessee;dDepartment of Pediatrics, University of Cincinnati College ofMedicine, Cincinnati Hospital Children’s Medical Center,Cincinnati, Ohio; eDepartment of Psychiatry, Oregon Health andScience University, Portland, Oregon; fHolland Bloorview KidsRehabilitation Hospital, Toronto, Ontario, Canada; gKaiserPermanente Northern, San Jose, California; hMassGeneralHospital for Children, Boston, Massachusetts; iDepartment ofPediatrics, Nationwide Children’s Hospital, Columbus, Ohio; andjDepartments of Neurology and Pediatrics, Baylor College ofMedicine, Houston, Texas

KEY WORDSactigraphy, education, sleep, sleep latency

ABBREVIATIONSASD—autism spectrum disorderATN—Autism Treatment NetworkCSHQ—Children’s Sleep Habits QuestionnaireNICHQ—National Initiative for Children’s Healthcare QualityRCT—randomized controlled trial

This manuscript has been read and approved by all authors.This paper is unique and not under consideration by any otherpublication and has not been published elsewhere.

www.pediatrics.org/cgi/doi/10.1542/peds.2012-0900I

doi:10.1542/peds.2012-0900I

Accepted for publication Aug 8, 2012

Address correspondence to Beth Malow, MD, MS, Burry Chair inCognitive Childhood Development, Director, Vanderbilt SleepDisorders Division, 1161 21st Avenue South, Room A-0116,Nashville, TN 37232. E-mail: [email protected]

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2012 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they haveno financial relationships relevant to this article to disclose.

S106 MALOW et al by guest on November 30, 2020www.aappublications.org/newsDownloaded from

mailto:[email protected]

Approximately 1 in 110 children fulfillsthe Diagnostic and Statistical Manualof Mental Disorders, Fourth Edition,Text Revision, diagnostic criteria forautism spectrum disorders (ASDs)as defined by delayed or abnormalsocial interaction, language as used insocial communication, and/or restrictedrepetitive and stereotyped patternsof behavior, interests, and activities.1

Children who have ASD are at greaterrisk for developing sleep problems thantypically developing children. Researchhas documented that the prevalence ofsleep disturbances ranges from 53% to78% for children who have ASD com-pared with 26% to 32% for typically de-veloping children.2,3

The key components of pediatric in-somnia are repeated episodes of dif-ficulty initiating and/or maintainingsleep, including premature awaken-ings, leading to insufficient or poor-quality sleep. These episodes result infunctional impairment for the child orother family members.4 In typicallydeveloping children, the primary causeof insomnia is behaviorally based.5 Inthe ASD population, however, insomniais multifactorial. It includes not onlybehavioral issues but also medical,neurologic, and psychiatric comorbid-ities; it is also an adverse effect of themedications used to treat symptoms ofautism and these comorbidities.6

Typically developing children who haveinsomnia are at increased risk forneurobehavioral problems such asimpairments in cognition, mood, atten-tion, and behavior.5,7–9 Similar to thebehavioral morbidity associated withpediatric insomnia that is observed inthe general population, children whohave ASD and sleep problems are proneto more severe comorbid behavioraldisturbances compared with childrenwithout sleep disturbances.10 In addition,treating insomnia in children who haveneurodevelopmental disorders may im-prove problematic daytime behaviors.11

Despite theprevalenceof andmorbidityassociated with pediatric insomnia,there is evidence that sleepdisorders inchildren often go undetected and un-treated.12–14 Medical practitioners of-ten do not ask about sleep concerns orparents do not seek assistance.15 Manyparents have poor knowledge aboutsleep development and sleep prob-lems.16 This is particularly relevant tochildren who have ASD, in that parentsmay present to the pediatrician withconcerns regarding aggression, im-pulsivity, inattention/hyperactivity, orother behavioral issues that may besecondary to a sleep disorder. Thecontribution of the sleep disorder maybe undetected due to emphasis ontreating the behavioral issue as op-posed to identifying and treating theunderlying factors. This deemphasis ofunderlying factors may be due to theabsence of a standardized approachfor recognition and treatment of in-somnia in children who have ASD.

Guidelines exist for sleep screeningandintervention in typically developingchildren.17,18 Guidelines and empiricalsupport also exist for the effectivenessof behavioral treatment of bedtimeproblems and night wakings in chil-dren.18–21 Specific behavioral treat-ments supported include the following:unmodified extinction: leaving thechild’s bedroom after putting the childto bed and not returning until morningunless the child is ill or at risk for in-jury; extinction with parent presence:parent is present in the room with thechild but does not interact with himor her; graduated extinction: parentreturns to child’s bedroom to attendto child on request or agitation butincreases the time in between requestsby the child for the parent to return;preventive parent education: providingeducation to parent on sleep habitsand bedtime routine; bedtime fading:delaying bedtime to promote sleep andthen “fading” or advancing bedtime

once child is falling asleep easier; andscheduled awakenings: awakening thechild before a spontaneous awakening.Extinction and parent education havestrong empirical support whereas theother interventions are less confidentlysupported.18 To our knowledge, how-ever, there are no published guidelinesrelated to management of insomniain children who have ASD, includingscreening and treatment. The evidencethat children who have ASD are atgreater risk for insomnia and itsmorbidity suggests that sleep screen-ing in this population of children isextremely important. The ideal evalua-tion of insomnia in children who haveASD involves a comprehensive sleepassessment, as outlined in a recentreview.22

To facilitate the evaluation of childrenwith ASD for insomnia, the Autism Treat-ment Network (ATN) in association withthe National Initiative for Children’sHealthcare Quality (NICHQ) worked col-laboratively to develop the clinicalpractice pathway presented in this arti-cle. The intention of this clinical practicepathway is to emphasize the need forscreening of sleep problems in ASD andto provide a framework for decision-making related to best practices in thecare of children and adolescents withASD in primary care settings, when seenby a general pediatrician, primary careprovider, or autism medical specialist.The pathway is not intended to serve asthe sole source of guidance in the eval-uation of insomnia in children who haveASD or to replace clinical judgment, andit may not provide the only appropriateapproach to this challenge.

METHODS

Guideline Development

The ATN Sleep Committee consists ofpediatric sleep medicine specialists aswell as developmental pediatricians,neurologists, and psychiatrists. The

SUPPLEMENT ARTICLE

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clinical practice pathway was designedto assist primary care providers andothers working directly with familiesaffected by ASD in addressing the chal-lenge of insomnia with regard to iden-tification,assessment,andmanagement.

Insomnia was defined as “repeateddifficulty with sleep initiation, duration,consolidation, or quality that occursdespite age-appropriate time and op-portunity for sleep that results in day-time functional impairment for thechild and/or family.”18 The responses ofthe parents to selected questions onthe Children’s Sleep Habits Question-naire (CSHQ)23 identified those patientswho have insomnia.

After performing a systemic review ofthe literature, expert opinion and con-sensuswasused to formthebasisof thepractice pathway (Fig 1). The ATN SleepCommittee’s knowledge of the litera-ture and applicability to clinical prac-tice informed best practices, which inturn created an overarching approachto insomnia within ATN sites by theautism medical specialist.

Systematic Review of the Literature

We conducted a systematic literaturereview to find evidence regardingthe treatment of insomnia in children

diagnosed with ASD (questions andsearch terms available on request fromthe authors). We searched OVID, CINAHL,Embase, Database of Abstracts and Re-view Database of Abstracts of Reviewsand Effects, and the Cochrane Databaseof Systematic reviews databases, withsearches limited to primary and sec-ondary research conducted withhumans, published in the English lan-guage, involving children aged 0 to 18years, and published between January1995 and July 2010. Individual studieswere graded by using an adaptationof the GRADE system24 by 2 primaryreviewers and then reviewed by contentexperts for consensus. Discrepancieswere resolved by a third party.

Pilot Testing of the Pathway

The ATN selected 4 pilot sites (BaylorUniversity, Houston, Texas; OregonHealthandScienceUniversity, Portland,Oregon; Kaiser Permanente Northern,San Jose, California; University of Mis-souri, Columbia, Missouri) to test thefeasibility of the practice pathway andprovide information regarding neededmodifications. The pilot sites collecteddata to document adherence to thepractice pathway and participated inmonthly conference calls to provide

updates, understand variance, and re-commend changes. Working with theNICHQ, members of the ATN SleepCommittee refined and finalized thepractice pathway on the basis of feed-back from the pilot sites. In response torecommendations from the pilot sitesto increase feasibility, the NICHQ alsodeveloped a 1-page checklist designedto guide providers through the practicepathway (Fig 2).

RESULTS

Results of the Literature Review

The search identified 1528 articles. Af-ter removing review articles, com-mentaries, casestudieswith fewer than10 subjects, studies that included chil-dren who did not have ASD, non-intervention trials, and articles thatdid not address our target questions,20 articles remained (Table 1). Wereviewed the literature for studies re-lated to other aspects of the practicepathway (eg, screening for insomnia,identifying comorbidities, importanceof follow-up) in the ASD populationand were unable to identify evidence-based reports for aspects other thantreatment. A comprehensive review25

and consensus statement26 relatedto the pharmacologic management of

FIGURE 1Checklist for carrying out the practice pathway in children who have ASD and insomnia. CSHQ, Children’s Sleep Habits Questionnaire.


FIGURE 2Practice pathway for insomnia in children who have ASD.

SUPPLEMENT ARTICLE


TABLE1

Results

ofSystem

aticLiterature

Review

StudyandGrade

Sample

InterventionandDuration

MeasuresUsed

toArrive

atConclusion

Results

Conclusions

Pharmacologic

interventions

Aman

etal,20054

1Included:101

childrenaged

5to17

yfrom

Research

Units

onPediatricPsychopharmacology

Networkwith

ASD

16wk(nonresponders)to

6mo(responders)

given

placeboor

risperidone

Parent

reportsleeplog

Sleepproblemsandanxietyless

common

inrisperidonegroup

(P=.02;P=.05).Average

sleep

durationincreasedshort-term

(17min;40min)butnotb

eyond

6mo(29min).Adverseevents

scored

asmoderate(placebo

versus

risperidone,respectively):

somnolence(12%

vs37%),enuresis

(29%

vs33%),excessiveappetite

(10%

vs33%),rhinitis(8%vs

16%),

difficulty

waking(8%vs

12%),

andconstipation(12%

vs10%)

Risperidoneimproves

sleep

latencyinchildrenwith

ASD

butn

otsleepduration;high

ratesofadverseoutcom

es

RCT,levelII

Excluded:M

entalage

,18

mo,

positiveb-hum

anchorionic

gonadotropintestresultforgirls,

significant

medicalcondition,

previous

trialw

ithrisperidone,

historyofneuroleptic

malignant

syndrome,and/or

weight,

15kg

20to44.9kg

=0.5mgup

tomaximum

of2.5mg/day

Abnorm

alInvoluntary

Movem

entS

cale

,20

kg=similar,except

slow

erdosing

$45

kgstartedat0.5mgnightly

then

titratedto

amaximum

of3.5mg/day

individeddoses

Adverseeventsscored

asmild

ormoderate/severe

(parentreport)

Honomichletal,20024

2Included:17childrenaged

3to8y

with

autismrecruitedas

subset

oflarger

study(California)

4wkplaceboand4wk

intervention2CU/kg

porcinesecretin

intravenously;no

washout

CSHQ

Secretindidnotsignificantlyaffect

CSHQ

scores:Bedtim

eresistance

(Pre,m

ean:9[range:

6–17];Post,m

ean:8[range:6–13])

Secretindoes

notsignificantly

improvesleep-onsetd

elay,

duration,bedtimeresistance,

andnightw

akings

inchildren

with

ASD

RCT,levelIII

Excluded:notspecified

Sleepdiary(bedtim

e,sleep

onset,tim

e/durationnight

waking,morning

rise)

Sleep-onsetd

elay

(Pre,m

ean:2.1

[range:1–3];Post,mean:1.6

[range:1–3])

Nightw

akings

(Pre,m

ean:4.1[range:

3–7];Post,mean:3.6[range:3–5])

Sleepduration(Pre,m

ean:4.7[range:

3–7];post,mean:4.3[range:3–8])


TABLE1

Continued

StudyandGrade

Sample


MeasuresUsed

toArrive

atConclusion

Results

Conclusions

Ellaway

etal,20014

3Included:experimentalgroup

consistedof21

females

aged

7to

41y;recruitedfrom

previous

8-wktrial;controlgroup

included

62females

aged

4to30

yrecruitedfrom

AustralianRett

SyndromeRegister

100mg/kg

liquid

L-carnitine

twiceadayfor6mo

RettsyndromeSymptom

sSeverityIndex

Comparedwith

Rettsyndrome

controls,L-carnitine

significantlyimproved

sleep

efficiency

(P,

.03)

butn

otduration(P

=.57),latency

(P=.15),daytim

esleep(P

=.55),

ornightw

akings

(P=.25)

L-carnitinesupplementation

improves

sleepefficiency

but

notduration,latency,daytime

sleep,or

numberofnight

wakings

inchildrenwith

Rett

syndrome

Pre/post-control,

levelIII

Excluded:Notspecified

SF-36Health

Survey

Hand

apraxiascale

7-dsleepdiary

TriTrac-R3DErgometer

(Hem

okinetics,Inc,Madison

Wisconsin)

Poseyetal,20014

4Included:26childrenandyoung

adults,aged3to23

ywith

ASD

(Indiana);20hadcomorbid

intellectualdisability.M

irtazapine

was

prescribed

totarget

symptom

sofaggression,self-

injury,irritability,anxiety,

depression,insom

nia,and

interferingrepetitivebehavior

Mirtazapine

startingdose

of7.5mgdaily

with

dosage

increasesmadein7.5-mg

increm

entsup

toa

maximum

of45

mgdaily

individeddoses,based

onresponse

oftarget

symptom

sandside

effects(range:7.5–45

mg).Treatmentd

uration

ranged

from

11to368d

(meanduration:

1506

103d)

Clinicians

used

theCGIscaleto

rateseverityand

improvem

ent.Amodified

CGI

improvem

entitem

assessingsleepquality

was

also

included

Nine

participantsresponded(defined

accordingtoaCGIscore

ofmuch

improved

orvery

much

improved).Five

of9responders

show

edimproved

sleep.Of

17nonresponders,3show

edimproved

sleep.Statistically

significant

improvem

entw

asseen

ontheCGIseverity

ratings

ofsleep(P

=.002)

Mirtazapine

iseffectivein

improvingsleepquality

inchildrenwith

ASD

Pre/post-no

control,levelIII

Excluded:Notspecified

Rossietal,1999


2to20

ywith

ASD(University

ofBologna)

with

continuous

presence

($1y)

ofsevere

mooddisorders,

aggressiveness,and

hyperkinesia

Niaprazine

1mg/kg

perday

TIDfor60

dBehavioralSummarized

Evaluation(includedsleep

disorders;difficulty

falling

asleep,night

wakings,and

earlywaking.Scored

0to4

(absenttovery

severe)

Comparedwith

startofthe

treatm

ent,

BehavioralSummarized

Evaluationshow

edimprovem

entinsleepdisorders

bytheendofthetrial(P,

.001)

Niaprazine

iseffectivein

improvingsleeplatencyand

nightw

akings

inchildrenwith

ASD

Pre/post-no

control,levelIII

Excluded:childrennosographically

definedcongenitaloracquired

encephalopathy

Mingetal,20084


4to16

ywith

ASD(New

Jersey)andsleep

andbehavioraldisorders

Clonidine1tim

eperday,

initialdose

0.05

mgand

gradually

advanced

to0.1

mg;oraltablet.Duration

for6moto2y

Caregiverreport(average

bedtime,latency,numberof

wakings)before

andduring

treatm

ent

Sixteenof17

childrenexperienced

improved

sleepinitiation(2–5h

before

treatm

ent,0.5–2h

during

treatm

ent);16of17

with

sleepmaintenance

disorders

experiencedimprovem

ents;5

stillexperiencednightw

akings

Clonidineimprovessleeplatency

andwakings

inchildrenwith

developm

entaldisorders

SUPPLEMENT ARTICLE


TABLE1

Continued

StudyandGrade

Sample


MeasuresUsed

toArrive

atConclusion

Results

Conclusions

Retrospective

case

control,

levelIII

Excluded:not

specified

Otherbiologicagents

Adam

sandHolloway,20044


3to

8y

with

ASDwith

nochangesin

treatm

enttherapies

inprevious

2mo,andno

previous

useof

multivitaminsupplementsother

than

standard

children’s

multivitamin(Arizona)

Days0to24:1/8dose

ofSS-II

(standardmultivitamin),

increasedlinearlyto

maximum

CGI

Sleepandgastrointestinalsymptom

sas

evidencedby

CGIscore

improved

comparedwith

placebo(P

=.03)

Moderate-dose

multivitamin

(including

vitaminB 6

and

vitaminC)

may

have

apositiveimpacton

CGIsleep

scoreinchildrenwith

ASD

RCTlevelII

Excluded:not

specified

Days25

to34:heldmaximum

dose

ofSS-II

Bloodandurinesample(plasm

aB 6,pyridoxine,pyridoxal,

pyridoxamine,a2lipoicacid,

vitaminC)

Days

35to50:gradual

transitiontoSS-III

Days

50to90:continued

SS-III;fulldose

1ml/5lb

TIDwith

food

foratotal

daily

intake

of3ml/5lb

body

weight

Dosm

anetal,20074


2to

5y

diagnosedwith

autismwith

ferritinmeasuredpreviously

(Toronto)

6mgelem

entaliron/kg

perdayfor8wk

SleepDisturbanceScalefor

Children

Perthesleepdisturbancescale

scores,restless

sleepimproved

significantly(29%

;P=.04)

and

35%hadimproved

sleep

latency;no

relationwas

found

with

ferritin(P

=.61),irritability

(P=.83),orPeriodicLeg

Movem

entsDuring

Sleep

Scale(P

=.82)

Oraliron

supplementation

improves

restless

sleepin

childrenwith

ASDbutdoesn

otaffectirritability,sleep

latency,or

periodicleg

movem

ents

Pre/post-control,levelII

Excluded:currentlytaking

iron

supplementation

Ifnottolerated,received

60mg/dayof

microencapsulated

powderedelem

entaliron

PeriodicLegMovem

ents

During

SleepScale

MeanferritinandMCV

increased

significantly(16to29

mg/L)

Bloodsample(M

CV,m

ercury,

albumin,vitaminB 1

2,serum

ferritin,transferrin)


TABLE1

Continued

StudyandGrade

Sample


MeasuresUsed

toArrive

atConclusion

Results

Conclusions

Wrightetal,20114

9Included:20children,aged

4to16

ywith

ASDandprolongedsleep

latency,excessivenightw

aking,

and/or

reducedtotalsleep

time.

Childrenhadundergonebehavior

managem

entthatwas

not

successfulandwerefree

ofpsychotropicmedications

Melatonin2mg,30

to40

min

before

plannedsleep,or

placeboandthen

crossed

over

totheotheragent.

Thedose

was

increased

bytheparent

every3

nightsby

2mgto

amaximum

doseof10

mg

until“good”

sleepwas

achieved,definedas

animprovem

entof$

50%.

Treatm

entphase

lasted

3moforeach

agentw

itha1mowashout

Daily

sleepdiaries(time

melatonintaken,bedtime,

sleeptim

e,nightw

akings,

timeaw

ake)

werecollected

everymonth

for9mo

Meansleeplatencywas

lower

(P=.004)andtotalsleep

timewas

longer

(P=.002)during

melatonintreatm

entcom

pared

with

placebo.Nightw

akings

did

notimprove(P

=.2)

Melatoninimproves

sleep

latencyandtotalsleep

timein

childrenwith

ASDbutn

otnightw

akings

RCT,levelIII

Excluded:childrenpreviouslyor

currently

onmelatonin,those

currently

onpsychotropic

medications,and

thosewith

other

neurodevelopmentaldisorders

such

asFragile

XorRettsyndrome

Sleepdifficulties

questionnaire

Dyssom

niasubscaleimproved

with

treatm

ent(P=.04)

butnot

parasomnia,sleepapnea,or

othersleepdisorders

Garstang

andWallis,20062

7Included:7

childrenaged

4to16

ywith

autismandsleeping

difficulty

(atleast1hsleeplatencyand/or

nightw

aking4tim

esperweekfor

thelast6mo)

(UnitedKingdom)

Placeboor

5mgmelatonin

for4wk,washout

1wk,

then

reversed

for4wk

Parentalsleepcharts(total

sleeptim

e,sleeplatency,

nightw

akings,m

orning

awakening)

Baseline,placebo,andmelatonin

values

respectively:Sleep

latencyimproved

1.54

hversus

baseline(2.6h[CI:2.28–2.93];

1.91

h[CI:1.78–2.03];1.06

h[CI:0.98–1.13])

Melatoninisan

effective

treatm

enttoimprovesleep

latencynumberofnight

wakings

andsleepduration

RCT,levelII

Excluded:childrenpreviously/

currently

usingmelatoninand/or

taking

sedativemedications

for

,4wk

Wakings

pernightd

ecreased

by0.27

pernightversusbaseline

(0.35[CI:0.18–0.53];0.26

[CI:0.20–0.34];0.08

[CI:0.04–0.12])

Durationincreasedby

1.79

hversus

baseline(8.05h[CI:7.65–8.44];

8.75

h[CI:8.56–8.98];9.84

h[CI:9.68–9.99])

SUPPLEMENT ARTICLE


TABLE1

Continued

StudyandGrade

Sample


MeasuresUsed

toArrive

atConclusion

Results

Conclusions

Wirojanan

etal,20092


2to15

ywith

autismand/or

Fragile

Xsyndromewho

reported

sleep

problems(California)

Placeboor

3mgmelatonin

given30

minbefore

bedtimefor2wk,then

reversed

for2wk(no

washout)

Sleepdiary(sleep

latency,

duration,sleeponset,number

ofnightw

akings)

Comparedwith

placebo,sleep

durationimproved

in9of12

participantsby

21min(P

=.057;

effectsize:2.12),sleep

latency

improved

in11

of12

participantsby

28min(P

=.10;

effectsize:1.79),sleep

onset

improved

by42

min(P

=.017;

effectsize:2.80),and

awakenings

wereimproved

by0.07

butwereinsignificant

(P=.73;effectsize:0.3540)

Melatoninisan

effective

treatm

enttoimprovesleep

duration,sleeplatency,and

sleeponsettimebutnotnight

wakings

RCTlevelII

Excluded:not

specified

Actiw

atch

(PhilipsRespironics,

Bend,Oregon)

Paavonen

etal,20035

0Included:15children5to17

ydiagnosedwith

Asperger’s

syndromeandsevere

sleep

problemsinlast3mo(Helsinki)

Received

3mgofmelatonin

30minbeforebedfor14d

Children’sSelf-ReportforSleep

Problems

Melatoninimproved

nocturnal

activity

(31.39

67.86

to18.746

4.99;P

=.041)andsleeplatency

(from40.026

24.09to21.826

9.64;P

=.002)butincreased

numberofwakings

(from15.146

6.12

to17.856

6.25;P

=.048).

Nosignificant

changeswere

foundinsleepefficiency

(85.13

65.57

to86.036

4.62;P

=.331)

orduration(477.406

55.56

to480.48

650.71;P=.572).

Melatoninisan

effective

treatm

enttoimprove

nocturnalactivity

andsleep

latencybutnotnightw

akings,

sleepefficiency,ordurationin

childrenwith

Asperger’s

syndrome

Pre/post-control,LevelII

Excluded:childrentaking

psychotropicmedications

orwith

major

psychiatric

comorbidity

SleepDisturbanceScalefor

Children

CBCL

KarolinskaSleepiness

Scale

Teacher’s

DaytimeSleepiness

Questionnaire

Actigraphy


TABLE1

Continued

StudyandGrade

Sample


MeasuresUsed

toArrive

atConclusion

Results

Conclusions

Giannottietal,20065


2.6to9.6y

with

autismandCARS

score

,29.5with

sleepdisorder

(.45

minsleeplatency,.3tim

esper

weeknightwakings,and

waking

before

5AM

.3tim

esperweek)

(Italy)

6-to

24-mo(n

=25

and

n=16,respectively)

study

CSHQ

CSHQ

values

from

baselineto6mo

weresignificantlyimproved

(65

vs43;P

,.001).CSHQ

values

regardinglatency,duration,

resistance,anxiety,night

wakings,and

daytime

sleepiness

weresignificantly

improved

(P,

.001).Sleep-

disordered

breathingalso

improved

(P,

.01).Sleep

diariesshow

edimprovem

ents

indurationby

2.6h(P

,.001),

awaketim

eaftersleeponsetb

yfrom

70to10

min(P

,.001),

cosleeping

in55%(P

,.001),

parentalpresence

atbedtimein

63%(P

,.001),andbedtime

irregularityin61%(P

,.001).

Thosewho

continued24

mo

show

edsignificant

improvem

entinCSHQ

scores

inyears1and2(63vs

44vs

44;

P,

.001)

Melatoninisan

effective

treatm

enttoimprovesleep

duration,latency,numberof

nightwakings,and

bedtime

resistance

inchildrenwith

ASD

Pre/post-control,levelII

Excluded:childrenwith

autism

diagnosisbutw

ithCARS

score

belowcutoff,coexisting

conditions,and/or

taking

medications

for6mopreviously

3mgcontrolled-release

melatonin30

to40

min

before

bedtime(1

mgFR

and2mgCR)

Sleepdiary(bed

time,rise

time,

duration,nightw

akings

and

duration,daynaps)

Childrenadvisedtogive2mg

FRischildrenaw

okefor

.15

minduring

thenight

Physiciancouldincrease

dose

tomaximum

of4mg

inchildrenaged

,4yand

upto6mginchildren

aged

.4y

Malow

etal,20115


3to9y

with

ASDandsleep-onsetdelay

of$30

minon

$3nightsperweek

Two-weekacclimation

phase:inertliquid30

min

before

bedtime

Actigraphy;CSHQ

With

melatonintreatm

ent(compared

with

acclimationphase),

statisticallysignificant

improvem

entswereseen

insleeplatency(42.9to21.6min;

P,

.0001)

butnottotalsleep

timeor

waketim

eaftersleeponset

Melatoninisan

effective

treatm

entofsleeplatency,

andimproves

aspectsof

daytimebehavior

and

parentingstress

inchildren

with

ASD.Itissafeandwell

tolerated

SUPPLEMENT ARTICLE


TABLE1

Continued

StudyandGrade

Sample


MeasuresUsed

toArrive

atConclusion

Results

Conclusions

Pre/post-control,LevelII


epilepsyor

taking

psychotropicmedications.

Before

melatonintreatm

ent,

medicalcomorbiditieswere

addressed,andparentsreceived

sleepeducationtraining

Optionalescalatingdose

protocolbasedon

3-wk

periods.Dose

was

escalatedfrom

1mgto3

mgto6mgbasedon

response

(ifasatisfactory

response

occurred,

definedas

falling

asleep

within30

minon

$5

nightsperweekby

actigraphy,thedose

was

notescalated)

CBCL,RBS,PSI.Laboratory

findings

(CBC,m

etabolic

profileincludingliver

and

renalfunction,corticotropin,

cortisol,estrogen,

testosterone,FSH,LH,and

prolactin).HagueSide

Effects

Scale

Significantlysignificant

improvem

entswerealso

notedinCSHQ

subscalesof

sleep-onsetd

elay

andsleep

duration,CBCL

subscalesof

withdraw

n,attention-deficit/

hyperactivity,and

affective,

RBSstereotypedand

compulsive,andtheDifficult

Child

subscaleon

thePSI.No

change

inlaboratory

findings.

Loosestoolsin1child;no

otheradverseeffects

Andersen

etal,20083

0Included:107

childrenaged

2to18

ydiagnosedwith

autismpreviously

recommendedtotake

melatonin

sleepdisorder

(Tennessee)

Aged

,6y,.75-1mg

melatonin30

to60

min

before

bed.After2wk,if

noresponse,increased

by1mgevery2wkup

to3mg

Chartreviewofclinicnotes

(including

sleephygiene,

otherpsychiatricconditions,

severityofASD,useof

medications)

Afterinitiation,25%with

sleep

problemsno

longer

aconcern;

60%hadimproved

sleepbut

stillhadconcerns;for

13%sleepproblemsremained

amajor

concern,and1%

reported

worse

sleepafter

treatm

ent.Threechildren

hadadverseeffects(m

orning

sleepiness

and/or

increased

enuresis)

Melatoninisasafe,effective

treatm

enttoreduce

sleepproblemsin

childrenwith

ASD

Pre/post-Nocontrol,

levelIII


adiagnosis

ofbipolardisorder

Aged

$6y,1.5mgmelatonin

30to60

minbefore

bed

timeIfno

response,

increaseddose

to3mg

after2wk

Sleepdiary

Allchildren:ifno

response

after4wk,increase

dose

to6mg

Behavioral/educational

interventions

Reed

etal,20093

1Included:20familiesofchildrenaged

3to10

ywith

clinicaldiagnosisof

ASDwith

sleepconcerns

(Tennessee)

•Three2-hsessions

for3

consecutiveweeks;

follow-up1moafterend

CSHQ

Educationalinterventionshow

edimproved

CSHQ

scores

for

bedtimeresistance

(P=.001),

latency(P

=.004),duration

(P=.003),andsleepanxiety

(P=.022)butn

otnightw

akings

(P=.508),parasomnia(P

=.607),

sleep-disordered

breathing

(P=.625),anddaytime

sleepiness

(P=.096)

Educationalinterventionwith

parentsimproves

bedtime

resistance,latency,duration,

andsleepanxietybutnotnight

wakings,earlymorning

waking,parasomnias,sleep

disordered

breathing,or

daytimesleepiness

inchildrenwith

autism


TABLE1

Continued

StudyandGrade

Sample


MeasuresUsed

toArrive

atConclusion

Results

Conclusions

Pre/post-nocontrol,

levelII


primary

sleepdisorderssuch

assleep

apnea,narcolepsy,and

neurologic/m

edicalconditions

thatmaycontributetodisordered

sleep

Session1:established

daytimeandnighttime

habitsandabedtime

routinebasedon

FISH

and

CSHQ

Actigraphy

Actigraphyshow

edimproved

sleep

latency(62.26

33.33minvs

45.66

27.6;P

=.039)butn

otwakingaftersleeponset

(24.56

9.8vs

32.26

24.7min;

P=1.0)

Session2:Strategies

tominimizenightwaking

andearlymorning

waking

Latency,duration,night

wakings

71%ofparentsreported

fewer

nights

cosleeping;33%

reported

improvem

entinearlymorning

waking

Session3:address

individualsleep

concerns

Weiskop

etal,20053

2Included:13children(across

13families)aged

5ywith

either

Fragile

Xsyndrome

(n=7)

orASD(n

=6)

with

perceivedsleepdifficulty

(Australia)

Five

sessions

over

7wkwith

weeklytelephonecalls;

follow-upat3and12

mo

SleepDiary(behavior,lightsout,

sleeponset,waking,

cosleeping,m

orning

wake

time)

Baselinecomparedwith

intervention:

4.6%

moderatedeteriorationof

sleepbehaviors,25%no

change,

29.7%moderateimprovem

ent,

and40.6%substantial

improvem

ents

Educationalinterventionwith

parentsimproved

sleep

latencyandnightw

akings

but

notd

urationinchildrenwith

developm

entaldisabilities

Case

series,levelIII

Excluded:excludedifdiagnosed

with

epilepsyand/or

ifdiagnosedwith

ASD,were

nottobe

taking

medication

Session1:goalsetting


3mo:

1.6%

substantialdeterioration,

4.8%

moderatedeterioration,

27%no

change,23.8%

moderateimprovem

ent,

and41.3%substantial

improvem

ent

Session2:learning

theory;

antecedentsand

consequences.Created

interventionwith

reinforcem

entand

visual

representation


12mo:

7.7%

moderatedeterioration,

19.2%no

change,26.9%

moderateimprovem

ent,

and46.2%substantial

improvem

ent

Session3:effective

instructions

andpartner

supportstrategies

Sleeplatencyimproved

in6of10

(60%

)

Session4:extinction

techniques

Nightw

akingimproved

for7of10

(70%

)

Session5:review

session

Durationwas

variableandunchanged

Cosleeping

was

also

addressed

100%

ofparentsreported

improved

sleepbut50%

stillconsidered

sleep

anissue

SUPPLEMENT ARTICLE


TABLE1

Continued

StudyandGrade

Sample


MeasuresUsed

toArrive

atConclusion

Results

Conclusions

Complem

entary

and

alternativemedicine

Piravejetal,2009


3to10

ydiagnosedwith

autism;30were

putintocontrolgroup

(SI)and30

wereexperimental(SI+TTM)

(Thailand)

Two60-minstandard

SIor

Two60-minTTMandSIfor

8wk

Sleepdiary

Massage

improved

sleepscores

(11.5vs

5.3;P,

.001).Standard

SIimproved

sleepbehavior

(13.9

vs8.2;P,

.001).Thedifference

betweenpre-andpost-sleep

behavior

scores

ofthecontrol

andmassage

groups

werenot


(5.7vs

6.3respectively;P=.85)

TT,beforebedtimeimproves

sleepinchildrenwith

ASDbut

notm

orethan

comparedwith

standard

SI

RCT,levelII

Excluded:those

with

contraindications

forTTMand

thoseunabletocomplete80%of

treatm

ent(13

massages)

Two60-minTTMandSI

for8wk

Williams,2006


12to15

ydiagnosedwith

ASDfrom

aresidentialschoolfor

children

with

autism(UnitedKingdom)

Threeadministrations

ofarom

atherapy(2%

lavenderoilingrapeseed

oil)over24

dviamassage

offootandleg∼2hours

before

bed

Sleepdiaryrecorded

bystaffon

30-minintervalrounds

(sleep

onset,duration,wakings)

Participantsdidnotdemonstrate


sleep-

onsettime(F=1.27;df=

4.15,41.5;

P=.30).Night

wakings

didnot

differwith

andwithout

arom

atherapy

(x2=20.19;

df=16;P

=.21).Sleep

duration

was

notaffected

byarom

atherapy

(F=0.59;

df=16,160;P

,.89)

Arom

atherapyisnotaneffective

treatm

enttoaffectsleep

onset,duration,andnight

wakings

Case

series

levelII

Excluded:nonespecified

Escalona

etal,20013


3to6y

recruitedfrom

schoolforchildren

with

autism(Florida)

For1mo,received

15-min

massage

therapyby

parents(trained

bytherapist)or

15minof

readingbefore

bedtime

Sleepdiaries(fussing,

restlessness,crying,self-

stimulatingbehavior,and

numberoftim

eschild

leftthe

bed)

Greaterdeclines

forthemassage

therapygroupwith

regard

tofussing/restlessness,crying,

self-stimulatingbehavior,and

gettingoutofbed(actual

numbers

notp

rovided;only

provided

statisticsfor

day-tim

ebehavior)

Massage

before

beddecreases

fussing/restlessness,crying,

self-stimulatingbehavior,and

gettingoutofbed

inchildren

with

ASDmorethan

reading

RCT,levelIV

Excluded:notspecified

CARS,Childhood

Autism

RatingScale;CBC,completebloodcellcount;CBCL,ChildBehavior

Checklist;CGI,ClinicalGlobalImpression;CI,confidenceinterval;CR,controlledrelease;FISH,Fam

ilyInventoryofSleepHabits;FR,fastrelease;FSH,follicle-

stimulatinghorm

one;LH,luteinizing

horm

one;MCV,m

eancorpuscularvolume;PSI,ParentalStress

Index;RBS,RepetitiveBehavior

Scale;SI,Sensory

Integration;SS,SpectrumSupport;TTM,ThaiTraditionalM

assage.


insomnia in children (not specific toASD) were identified.

The results of the systematic literaturereview demonstrate that treatmenttrials are limited in the ASD population.There are 3 categories of treatment:pharmacologic/biologic treatments,behavioral/educational interventions,and complementary and alternativemedicine.

Theevidencebase todateshows limitedevidence for the use of medications totreat insomnia in children who haveASD. The most evidence exists for theuse of supplemental melatonin, anindoleamine with sleep-promoting andchronobiotic (sleep phase shifting)properties considered a nutritionalsupplement by the US Food and DrugAdministration. Several small, ran-domized controlled trials (RCTs) dem-onstrated the efficacy of supplementalmelatonin in treating insomnia inchildren who have ASD,27–29 althoughlarger studies are needed. Melatoninseems to be relatively safe based onthese trials and on other series.30

Other pharmacologic interventionssuch as risperidone, secretin, L-carni-tine, niaprazine, mirtazapine, and clo-nidine, as well as multivitamins andiron, have limited evidence supportingtheir use in treating insomnia in ASD.The research evidence to date does notsupport the efficacy of other supple-ments or vitamins.

Behavioral interventions are clearlybeneficial for typically developing chil-dren experiencing significant insom-nia.21 However, few treatment trialsfound that behavioral treatments pro-vide consistent success rates in chil-dren who have ASD, particularly thoseexperiencing sleep-onset insomnia. Thesystematic review of the literature iden-tified 2 studies examining the efficacyof behavioral treatment of insomniain children who have ASD.31,32 Each ofthese studies demonstrated statisti-cally significant improvements in sleepTA

BLE2

SleepQuestionnaire

Options

Questionnaire

Description

Form

atRespondent

CSHQ

(Owensetal,2000)

36Assesses

sleepbehaviorsacross

arangeofbehavioraland

medicaldimensionsinchildrenaged

4to10

yForty-five

itemsthatrollinto8subscales:bedtimeresistance,

sleeponsetdelay,sleep

duration,sleepanxiety,nightw

akings,

parasomnias,sleep-disorderedbreathing,anddaytime

sleepiness

Parent

Children’sSleepHabitsQuestionnaire

inToddlers

andPreschool

Children(Goodlin-Jones

etal,2008)

23

Assesses

theCSHQ

(see

above)

inchildrenaged

2to5.5ywith

autism,developmentaldelay

withoutautism,and

typically

developing

children

Sameas

theCSHQ

(above)

Parent

SleepDisturbanceScaleforChildren3

7Characterizessleepdisordersoverthepast6moinchildrenaged

5to

15y

Twenty-sixitemsthatroleinto6subscales:sleepinitiationand

maintenance,daytim

esleepiness,sleep

arousal,andsleep-

disordered

breathing

Parent

Family

InventoryofSleepHabits38

Autismspecificquestionnaireassessingsleephygieneinchildren

aged

3to10

yTwelve

items,includingdaytimeandprebedtim

ehabits,bedtim

eroutine,andsleepenvironm

ent

Parent

BehavioralEvaluationofDisordersofSleepScale3

9Assesses

sleepbehaviorsinchildrenaged

5to12

yFive

typesofsleepproblems:expressive

sleepdisturbances;

sensitivitytotheenvironm

ent;disorientedaw

akening;sleep

facilitators;andapnea/bruxism

Parent

BEARS1

7Assesses

5sleepdomains

inchildrenaged

5to18

yFivesleepdomains:bedtim

eproblems(difficulty

goingtobedand

falling

asleep);excessivedaytimesleepiness

(includes

behaviorstypically

associated

with

daytimesomnolencein

children);awakenings

during

thenight;regularityofsleep/

wakecycles

(bedtim

e,waketim

e)andaveragesleepduration;

andsnoring

Parent

Adolescent

SleepWakeScale4

0Assesses

sleepquality

inadolescentsaged

11to21

yTwenty-eight

itemsroleinto5subscales:goingtobed,falling

asleep,awakening,reinitiatingsleep,andwakefulness

Adolescent

BEARS,B=Bedtimeproblems,E=ExcessiveDaytimeSleepiness,A

=Aw

akenings

During

theNight,R=RegularityandDurationofSleep,S=Snoring.

SUPPLEMENT ARTICLE


posttreatment. Both studies used mul-ticomponent treatments, although theyvaried with respect to the specificcomponents of treatment. However,they were representative of treatmentscommonly used in clinical practice aswell as supported as effective in thegeneral pediatric population. Bothstudies used extinction and positivereinforcement as treatments. Bothstudies provided parent training, asfollows: (1) identifying a treatmentgoal/treatment target for therapy; (2)discussion of how the sleep problem ismaintained by conditioning/learning;and (3) emphasis on establishing a de-velopmentally appropriate bedtimeand a consistent bedtime routine. Othertreatment components addressed in a

single study included sleep hygiene in-structions, use of effective instructions/directions to shape appropriate sleepbehavior, and use of the bedtime passprotocol.23 The studies did not addressrelative efficacy of these individual treat-ment components.

Complementary and alternative medi-cine therapies addressed in the litera-ture review include massage therapyand aromatherapy.33–35 The systematicreview found no evidence to supportthese therapies for insomnia in chil-dren who have ASD. Neither of thegraded studies examining the efficacyof massage therapy or aromatherapyfor insomnia in children who have ASDled to statistically significant improve-ments in sleep posttreatment.33–35

Results of the GuidelineDevelopment

Basedon the feasibility testing, a numberof observations resulted in the devel-opment of resources to assist cliniciansin theapplicationof thepracticepathway.After reviewing the literature and con-ducting pilot testing, the ATN SleepCommittee developed and refined theinsomniapracticepathwayandmade thefollowing consensus recommendations:

A. General pediatricians, family careproviders, and autism medical spe-cialists should screen all childrenwho have ASD for insomnia.

This screening is best done by askinga short series of questions targetinginsomnia, such as those from theCSHQ, and asking if the parent consid-ers these a problem. These questionsare: (1) child falls asleep within 20minutes after going to bed; (2) childfalls asleep in parent’s or sibling’s bed;(3) child sleeps too little; and (4) childawakens once during the night. Thesequestions were selected on the basisof review of the CSHQ and expert con-sensus. The ATN database was alsoreviewed (n = 4887), and we foundthat 81% of parents who reportedthat their child awakening more thanonce during the night was a problemalso answered affirmatively to thequestion “Does your child awaken onceduring the night?” Therefore, to limitthe questions asked, we did not in-clude “Does your child awaken morethan once during the night?” Askingspecific questions is essential becauseparents may not volunteer concernsabout insomnia given their concernswith behavioral issues (although theseissues may be secondary to the in-somnia). Identifying significant insom-nia is paramount given its impact ondaytime functioning, not only for thechild with ASD but also the family. Table2 lists available questionnaires.

B. The evaluation of insomnia shouldinclude attention to medical

TABLE 3 Questionnaire to Help Identify Underlying Medical Conditions


contributors that can affect sleep(including neurologic conditions andother sleep disorders that contrib-ute to insomnia).

These contributors should be ad-dressed because their treatment mayimprove insomnia. Within the ATN, wehave developed a list of questions formedical contributors, including gas-trointestinal disorders, epilepsy, pain,nutritional issues, and other under-lying sleep disorders responsible forinsomnia, including sleep-disoderedbreathing and restless legs symptoms(Table 3) that pediatricians can in-corporate within their review of sys-tems. Psychiatric conditions, such asanxiety, depression, and bipolar disor-der, should be considered becausethese may contribute to insomnia. Fi-nally, because many medications con-tribute to insomnia, a careful review ofmedications should be performed.

C. Educational/behavioral interventionsare the first line of treatment, afterexcluding medical contributors. How-ever, if an educational (behavioral)approach does not seem feasible,or the intensity of symptoms hasreached a crisis point, the use of phar-macologic treatment is considered.

Educational/behavioral approaches tothe treatment of insomnia are advo-cated as a first-line treatment in typi-cally developing children.21 In childrenwho have ASD, educational/behavioralapproaches are also recommended,especially because these children maynot be capable of expressing adverseeffects caused by the medications. Thecore behavioral deficits associatedwith ASD may impede the establish-ment of sound bedtime behaviors androutines. These include: (1) difficultywith emotional regulation (eg, ability tocalm self); (2) difficulty transitioningfrom preferred or stimulating activi-ties to sleep; and (3) deficits in com-munication skills affecting a child’sunderstanding of the expectations of

parents related to going to bed and fall-ing asleep. Conversely, given preferencesfor sameness and routine, children whohave ASD may adapt well to establish-ment of bedtime routines, especially ifvisual schedules are implemented.

The ATN has developed an educationaltoolkit for parents that consists ofpamphlets to promote good sleephabits; a survey to assess for habitsthat may interfere with sleep; samplebedtime routines, including a visualsupports library, tip sheets for imple-menting the bedtime routine, andmanaging night wakings; and a sleepdiary. The toolkit is being tested forfeasibility in an ongoing research pro-ject funded by the Health Resourcesand Services Administration of parentsleep education at 4 ATN sites and isalso being used in clinical practicethroughout the network. As with othereducational/behavioral approaches,the success of this toolkit depends onappropriate implementation by par-ents, with the guidance provided bypractitioners an essential element formany families. Families can often beencouraged to implement educational/behavioral strategies when presentedwith these tools, especially if they re-ceive hands-on instruction in the toolsand are providedwith an explanation ofwhy a behavioral approach is recom-mended. However, some families maybe in a state of crisis or may not bewilling or able to use the behavioraltools. These familiesmay be challengedby difficult daytime behaviors in theirchild or by financial concerns. Thesechildren might require pharmacologictreatment. In addition, practitionersmaynot be able to provide sufficient in-struction in the tools for a family to besuccessful with their implementation.Therefore, there is the option in thepractice pathway (Fig 2, Box 5b) ofmedication or consultation to a sleepspecialist if the family is unwilling orunable to use an educational approach,

depending on the comfort level of thepediatrician.

Behavioral Treatments for Insomnia

The behavioral treatments most com-monly used to treat insomnia in chil-dren who have ASD include behavioralmodification strategies such as extinc-tion (eg, withdrawal of reinforcementfor inappropriate bedtime behaviors)and positive reinforcement of adaptivesleep behavior. Sleep hygiene instruc-tions (eg, appropriate sleep schedulesand routines) often accompany behav-ioral modification protocols. Behavioralinterventions are effective in the treat-ment of insomnia in typically developingchildren.21 However, the evidence basefor effectiveness of such interventions inchildren who have ASD is limited. Thedata from the literature review providepreliminary support for the use of be-havioral modification to treat insomniain children who have ASD. These datawere the basis for the development of aneducational toolkit used to guide behav-ioral management of insomnia in theinsomnia practice pathway.

Alternative Treatments for Insomnia

The most common alternative therapywith a presence in the literature is mas-sage therapy.33,35 However, the results donot demonstrate consistent, statisticallysignificant improvements in sleep.

Pharmacologic Treatments forInsomnia

Although medications and supplementsare often used to treat insomnia experi-enced by children and adolescents whohave ASD, the evidence base for phar-macologic treatment is limited. At thistime, there are nomedications approvedby the US Food and Drug Administrationfor pediatric insomnia. The most evi-dence exists for the use of melatonin.

D. Clinicians should assure timelyfollow-up to monitor progress andresolution of insomnia.

SUPPLEMENT ARTICLE


Assuring adequate follow-up is crucialwhen treating children who have ASDand significant insomnia. Follow-upshould occur within 2 weeks to 1month after beginning treatment. Theprovider and family should expect tosee some benefits and improvementswithin 4 weeks. Follow-up may be con-ducted by telephone or in person.Timely follow-up allows for fine-tuningof treatment interventions, support ofparents, and provision of referrals ifneeded. In addition to short-termfollow-up (eg, 1–2 months), at long-term follow-up (eg, 1-year visit) thesteps from the beginning of the prac-tice pathway should be repeated.

As outlined in the practice pathway,treatment of insomnia can be initiatedby the general pediatrician, primarycare provider, or autism medical spe-cialist. Many children will improve withthese initial interventions. Consultationwith a sleep specialist is indicated ifinsomnia is not improving with theseinitial interventions or when the in-somnia is particularly severe, causingsignificant daytime impairment orplacing the child at risk for harm whileawake during the night. For thosechildren who have ASD and are takingmultiple medications for sleep wheninitially assessed by the health careprovider, consultation with a sleepspecialist may be indicated, dependingon the comfort level of the provider.Other indications for consultation witha pediatric sleep specialist may includewhen underlying sleep disorders areresponsible for the sleeplessnesssymptoms (including sleep apnea,restless legs syndrome, periodic limbmovements of sleep, and unusual night-time behaviors [parasomnias] such assleepwalking or sleep terrors).

Results of the Field Testing

Results of the pilot phase indicatedchallenges in implementing the practicepathway due to a number of conflicts,

including: (1)competingdemandsonthepediatric provider in a busy clinicalpractice; (2) knowledge level of the pe-diatric provider; and (3) when consul-tation to the sleep specialist occurs,ensuring communication back to thepediatric provider.

In response to these barriers, we de-veloped the following resources: (1)a short set of screening questions forinsomnia as well as a checklist formedical conditions contributing to in-somnia (Table 3); and (2) a sleep edu-cation toolkit, available in hard copy aswell as on the internal ATN Web site(www.autismspeaks.org/atn) that willfacilitate parent teaching.

Additional issues were identified re-lated to provider comfort level in thefollowing areas: (1) assessing formedical or sleep contributors them-selves rather than referring to a spe-cialist, which led us to modify thepractice pathway to allow for bothoptions; (2) providing education tofamilies in use of the toolkit, which af-fected the length at which follow-upoccurred (eg, a second visit witha nurse educator might be needed fortoolkit implementation if the providerwas too busy to educate families at thetime of the initial clinic visit); and (3)treating insomnia with medications ontheir own versus referring to a sleepspecialist. When a child was referred tothe sleep specialist, ensuring that thesleep specialist communicated backto the provider regarding recommen-dations was also an issue related toapplying the practice pathway in ourfield testing, particularly as related tofollow-up care.

We modified the flow of the practicepathway in response to feedback dur-ing the field testing. Initially, the prac-tice pathway prioritized evaluationand treatment of medical contributorsbefore implementing educationalmeasures, such as the toolkit. However,based on the feedback of clinicians, the

evaluation/treatment of medical con-tributors and the implementation ofeducational measures became a paral-lel process as opposed to a sequential“first–then” approach.

DISCUSSION

We report here on the development ofa practice pathway for the evaluationand management of insomnia in chil-dren who have ASD. There are severalkey points of this practice pathway.First, general pediatricians, primarycare providers, and autism medicalspecialists should screen all childrenwho have ASD for insomnia becauseparents may not volunteer sleep con-cerns despite these concerns beingcontributors to medical comorbiditiesand behavioral issues. Second, theevaluation of insomnia should in-clude attention to medical contributorsthat can affect sleep, including othermedical problems that encompassgastrointestinal disorders, epilepsy,psychiatric comorbidities, medications,and sleep disorders including sleep-disordered breathing, restless legssyndrome (unpleasant sensations in thelegs associated with an urge to move),periodic limb movements of sleep(rhythmic leg kicks during sleep), andparasomnias (undesirable move-ments or behaviors during sleep,such as sleepwalking, sleep terrors, orconfusional arousals). In parallel withthis screening, the need for therapeu-tic intervention should be determined.We also determined that educational/behavioral interventions are the firstline of treatment, after excludingmedical contributors. If an educa-tional (behavioral) approach does notseem feasible, or the intensity ofsymptoms has reached a crisis point,the use of pharmacologic treat-ment is considered. Finally, cliniciansshould assure timely follow-up tomonitor progress and resolution ofinsomnia.


http://www.autismspeaks.org/atn

This practice pathway expands the lit-erature that currently exists for typi-cally developing children related toscreening and management.5,7–9 Therationale for developing a practicepathway that uniquely addresses thispopulation is because children whohave ASD, and their families, haveunique needs. For example, medical,neurologic, and psychiatric comorbid-ities are common in children who haveASD, as is the use of medications thatinfluence sleep. In addition, parents ofchildren who have ASD, struggling withthe stressors related to their child’sdisability and the often accompanyingbehavioral challenges, may not volun-teer sleep to be of concern. In turn,pediatric providers may not ask aboutsleep due to competing medical andbehavioral issues. Furthermore, sleepproblems are more common in chil-dren who have ASD than in childrenof typical development,2,3 and theirtreatment may impact favorably ondaytime behavior and family function-ing. Given these factors, we do recog-nize that children who have otherdisorders of neurodevelopment couldalso benefit from this practice pathway,as they share common features withchildren who have ASD, including

comorbid conditions, parental stres-sors, and prevalent sleep problems.

The systematic review of the availabletreatment literature allowed for therecognition that evidence-based stan-dards for the behavioral, pharmaco-logic, and other treatments of insomniain ASD are not yet available. Thus, muchof these guidelines reflect expertopinion given the absence of data. Ad-ditional studies are needed to establishthe efficacy and safety of supplementalmelatonin, as well as other pharma-cologic agents, in large RCTs. Similarstudies are needed to address the ef-ficacy of parent-based sleep educa-tional programs to address insomnia,as well as the combination of theseeducational programs with pharma-cologic strategies. Finally, the roleof nonpharmacologic methods (apartfrom educational therapies) warrantsstudy as well. As additional researchstudies are performed, the clinicalpathwaywill likely requiremodification.However, it is expected that the over-arching approach to insomnia in thechild who has ASD will not change. Al-though the practice pathway waspiloted at 4 ATN sites, the next stepsinvolve the wide dissemination ofthe practice pathway into pediatric

practices. We would also like to developa practice pathway for nonmedicalhealth professionals who are likely toprovide behavioral interventions, in-cluding psychologists.

Strengths of the study include the gath-ering of the following groups: experts insleep medicine from a variety of dis-ciplines, including neurology, psychiatry,pulmonary medicine, and psychology;engaged pediatricians specializingin ASD; and parents of children whohave ASD. Weaknesses include limitedevidence-basedstudiesonwhich tobasethe practice pathway, making it neces-sary to rely on expert opinion.

CONCLUSIONS

The practice pathway regarding theidentification of insomnia in childrenwho have ASD requires future fieldtesting in clinical settings but repre-sents a starting point to managing in-somnia in a growing population ofchildren with the most commonneurodevelopmental disability.

ACKNOWLEDGMENTThevaluableassistanceof themembersof the ATN Sleep Committee in re-viewing this document is gratefullyacknowledged.

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DOI: 10.1542/peds.2012-0900I2012;130;S106Pediatrics

Goldman, Rebecca Panzer, Daniel L. Coury and Dan G. GlazeBeth A. Malow, Kelly Byars, Kyle Johnson, Shelly Weiss, Pilar Bernal, Suzanne E.

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