Diagnosis and management of attention-deficit/hyperactivity disorder in children, young people, and...

mpbwpi“dMcsesydhnaAhaAdippaw

FUC1©d

6

The Diagnosis and Management ofAttention-Deficit/Hyperactivity Disorder in PreschoolChildren: The State of Our Knowledge and Practice

Benard P. Dreyer, MD

dtspwcsda

EG

tbptoAtAcSstsA

Alaoheb

J amie is a 3-year-old who is described by hisparents as “always in motion.” He does not sitstill for more than a few minutes and seems to

ove from one activity to another all day long. Hisarents complain that he does not want to look atooks when they try to read aloud to him and justants to turn the pages without paying attention to theictures or the story. Jamie constantly talks andnterrupts others, and according to his parents, hedrives everyone crazy.” Maria is 2½. Her motherreads going to the supermarket with her becausearia grabs at all the items in the store, frequently

ausing a “scene,” and not infrequently hurting her-elf. In fact, Maria has already been to the hospitalmergency room on three occasions for injuring her-elf due to her uncontrollable behavior. Tyrell is 4ears old and has been expelled from his preschool forisruptive behavior, not listening to the teacher, anditting other children. None of the other children in theeighborhood want to play with him. Jamie’s, Maria’s,nd Tyrell’s parents worry that their children havettention-Deficit/Hyperactivity Disorder (ADHD) andave sought advice from their pediatrician. The pedi-trician is concerned about making the diagnosis ofDHD in children of such a young age. How can sheistinguish between the inattention, exuberance, andmpulsivity that is part of the normal development ofreschool-aged children and behaviors that representathologic symptomatology? Perhaps these behaviorsre due to poor parenting or to poor parental copingith a temperamentally active child. Even if ADHD is

rom the Professor of Pediatrics, Department of Pediatrics, New Yorkniversity School of Medicine, New York, NY.urr Probl Pediatr Adolesc Health Care 2006;36:6-30538-5442/$ - see front matter2006 Mosby, Inc. All rights reserved.

roi:10.1016/j.cppeds.2005.10.001

iagnosed, what interventions are available or effec-ive? When, if ever, would it be appropriate to pre-cribe stimulant medication? These are questions thatediatricians are frequently faced with. This articleill review what is known about ADHD in preschool

hildren, including issues related to etiology, diagno-is, prevalence, comorbidities, psychosocial and aca-emic impairment, continuity with school-aged ADHD,nd therapy.

tiologyenetics and Neurobiology

There is strong evidence that ADHD and relatedraits (hyperactivity and inattention) are highly herita-le. Studies of families and siblings have shown thatarents and siblings of children with ADHD have awo- to eightfold increase in risk for ADHD.1 Numer-us twin studies have estimated the heritability ofDHD. These studies indicate that about 75 to 80% of

he etiology of ADHD can be explained by genetics.2

doption studies have also supported the large geneticomponent in the etiology of ADHD. In a study byprich and colleagues, while adoptive parents andiblings of ADHD children had low rates of ADHD (6o 8%) that were not different from a comparisonample, biological parents and siblings had rates ofDHD of 18 and 31%, respectively.3

In contrast to the large number of genetic studies ofDHD in school-aged children, only a few studies

ook at preschool children. In one twin study, hyper-ctivity was defined as greater than the 95th percentilen the Child Behavior Checklist/2-34 for symptoms ofyperactivity or inattention. The results of this studystimated the heritability of hyperactive/inattentiveehavior to be 70% in 3-year-olds and found a
emarkably similar heritability at ages 7, 10, and 12
Curr Probl Pediatr Adolesc Health Care, January 2006

ybrhsh

dtspcraaTcsisodpb

E

AftAtwdtuc“Ebas

apPaTms

iwsw

awTnoeanicswaThawatodgm

tccfshpeewyms

awsfvv

C

ears.5 Another twin study looking at hyperactiveehavior in 2- ,3-, and 4-year-olds showed heritabilityates of 70 to 80%.6 Thus there is good evidence thatyperactive/inattention behavior in young children,imilar to ADHD symptomatology in older children, isighly heritable.Molecular genetic studies have implicated the D4opamine receptor (DRD4) gene and the dopamineransporter (DAT) gene in the etiology of ADHD inchool-age children.7 The D4 dopamine receptor isrimarily found in areas of the brain involved withognition and emotion, and there is evidence that theseeceptors play important roles in attention, motivation,nd exploratory behavior. The DAT is the site ofction for psychostimulant drugs used to treat ADHD.herefore both of these genes have a physiologiconnection to the neurobiology of ADHD. Severaltudies have implicated these genes in hyperactive-mpulsive behavior in preschool children,8,9 demon-trating a continuity of genetic factors from younger tolder children. Nevertheless, ADHD is a complexisorder, and research concerning these genes is in areliminary phase. It is likely that other genes will alsoe identified.

nvironmental Factors

Despite the strong evidence for heritability ofDHD, there is a significant role for environmental

actors. Twin studies are likely to overestimate heri-ability. Their results are usually based on report ofDHD symptoms from a parent, who is likely to know

hat the twins are identical or fraternal.10 In addition,hile genetic etiology may be “necessary” for theiagnosis of ADHD, it may not be “sufficient.” Addi-ional environmental factors could be critical. It is alsonclear whether environmental factors may be uniqueauses of ADHD, or whether they always act as asecond hit” to a genetically predisposed individual.11

nvironmental factors implicated in ADHD includeiologic factors (such as prenatal and perinatal factorsnd chemical toxins) and family and psychosocialtressors.Biologic Factors. Mothers of children with ADHD

re more likely than others to have complications ofregnancy, including toxemia and lengthy labor.10

rematurity or small for gestational age are alsossociated with attentional problems in the child.12

hese factors, through hypoxemia and hypoperfusion,ay directly affect the developing brain, as has been

uggested by Lou.13 Low neonatal cerebral blood flow a

urr Probl Pediatr Adolesc Health Care, January 2006

n preterm neonates has been shown to be associatedith increased dopamine receptor availability in these

ame children during their adolescence in associationith the diagnosis of ADHD.14

Thapar and colleagues studied families with twinsnd found that maternal smoking during pregnancyas associated with ADHD symptoms in the child.his effect was in addition to the genetic effects, andonshared environmental influences on the diagnosisf ADHD.15 Animal studies suggest that prenatalxposure to nicotine may affect neural developmentnd neurotransmitters, causing an increase in brainicotinic receptors.16 Since nicotinic receptors arenvolved in dopamine regulation, there is a theoreticalonnection between maternal smoking and ADHDymptoms in the child. We also know that mothersho smoke have more complications of pregnancy

nd a higher frequency of low-birth-weight infants.hey may predispose their fetuses to increased risk forypoxemia. Thus, there are many other pathways, inddition to increased brain nicotinic receptors, throughhich maternal smoking may cause ADHD symptom-

tology.16 These results, however, must be viewed inhe context of the magnitude of the association, sincenly 1% of variance of ADHD symptomatology wasue to maternal smoking (as compared to 73% due toenetic factors and 26% due to nonshared environ-ental factors).15

Toxicity due to environmental lead has been showno be associated with learning and attention deficits inhildren 7 to 11 years of age.17 Mendelsohn andolleagues studied 12- to 36-month-old children andound significant correlations of low-level lead expo-ure (blood lead between 10 and 24.9 �g/dL) withyperactive-distractible behavior. This associationersisted even after controlling for possible confound-rs.18 Thus, there appears to be an association ofxposure to environmental lead, even at low levels,ith hyperactive and distractible behavior in veryoung children. As was the case with the effects ofaternal smoking, the effects of lead exposure are

mall.Konofal and colleagues showed that iron deficiency,

s defined by low serum ferritin levels, was associatedith ADHD diagnosis in a case-control study de-

ign.19 In addition, within the ADHD group, serumerritin levels were inversely correlated with the se-erity of ADHD, accounting for about 10% of theariance in ADHD severity. Since brain iron levels
ffect dopamine neurotransmission, there is a plausi-
7

btsccidacmltc

dcwbowbifshccptb

asmdoiAapoAtsttssto

vsoLshTnaoocs

bnpemmctsfbece

DCD

taFDitcrchonI

8

le biological mechanism for this association.20 Al-hough this study of children aged 4 to 14 years did notpecifically focus on preschool children, iron defi-iency is a problem that primarily affects younghildren. Therefore, we would anticipate effects ofron deficiency in the preschool age group. The causalirection of the association between iron deficiencynd ADHD symptoms demonstrated in this studyannot be assumed. While there was no evidence ofalnutrition in the ADHD group, it is possible that the

ower ferritin levels were a marker for poorer nutri-ional status in this group. In that case, ADHD mightause iron deficiency rather than the reverse.There is strong evidence that snoring, sleep-disor-ered breathing, and obstructive sleep apnea are asso-iated with hyperactive and inattentive behavior andith the diagnosis of ADHD.21 These findings haveeen well-documented in 4- to 5-year-olds as well aslder children.22 While up to one-third of childrenith frequent and loud snoring or sleep-disorderedreathing will display symptoms of hyperactivity andnattention,22 only 5% of children with ADHD areound to have obstructive sleep apnea.21 The relation-hip of ADHD and sleep is further complicated by theigher incidence of general sleep disturbances inhildren with ADHD. It seems prudent for the clini-ian to take a thorough sleep history in childrenresenting with symptoms of ADHD and evaluatehose children with snoring and sleep-disorderedreathing for obstructive sleep apnea.Psychosocial Factors. There is conflicting evidence

bout the relationship of psychosocial and familytressors and ADHD. There is an association ofaternal depression and ADHD in preschool chil-

ren23 and there is a reported association of psychos-cial adversity and ADHD symptom severity.10 Theres also evidence that preschool children who haveDHD associated with disruptive behavior problems

lso have more family dysfunction and parents withoorer parenting skills.23 Nevertheless the directional,r more likely transactional, relationship betweenDHD, disruptive behavior, and parenting compe-

ence is complex. It is likely that psychosocial stres-ors and lower parenting competence are nonspecificriggers of an underlying disorder, or are modifiers ofhe disorder, rather than true causes of ADHD.10,16 Asuch they may be the stressors that lead a geneticallyusceptible individual to a full-blown diagnosis, orhey may lead to worsening of symptoms and a range
f comorbid psychopathologies. a
There has been concern that excessive televisioniewing, especially occurring at an early age, mayhorten a child’s attention span and lead to symptomsf ADHD. Christakis and colleagues used the Nationalongitudinal Survey of Youth to assess the relation-hip of early television viewing at ages 1 and 3 withyperactivity and attentional problems at age 7.24

hey found a significant relationship between theumber of hours of television viewed and risk ofttentional and hyperactive problems. Although thedds ratios were statistically significant, they werenly slightly greater than one. In view of potentialonfounding, such a weak relationship is not stronglyupportive of a causative role for television viewing.Summary. ADHD has a strong genetic causativeasis, accounting for approximately 75% of its diag-osis. Nevertheless, there are a number of biologic andsychosocial factors that may play a deciding role inither triggering an underlying predisposition, or inodifying the severity of symptomatology. Althoughost studies of etiology have looked at school-aged

hildren with ADHD, there are a number of studieshat have focused on the etiology of ADHD in pre-chool children or on the determination of ADHD riskactors occurring early in life. In addition, most of theiologic and psychosocial risk factors are present inither the prenatal period, the perinatal period, or earlyhildhood and are likely to be implicated in thetiology of ADHD diagnosed in preschool children.

iagnosis and Prevalenceoncerns About Use of DSM-IV Criteria iniagnosis of ADHD in Preschool Children

The diagnosis of ADHD is generally made based onhe child meeting the criteria delineated in Diagnosticnd Statistical Manual of Mental Health Disordersourth Edition Text Revision (DSM-IV-TR).25 TheSM-IV criteria describe three subtypes of ADHD:

nattentive, hyperactive-impulsive, and combined. Forhe inattentive and hyperactive-impulsive subtypes,hildren must have at least six of nine symptoms in theespective subtype. For the combined subtype, thehild must meet criteria for both the inattentive and theyperactive impulsive subtypes. See Table 1 for a listf symptoms. These symptoms must occur “often,”ot occasionally, and persist for at least 6 months.mportantly, they must be severe enough to be “mal-
daptive and inconsistent with developmental level”

ayeaa

ftpowstctcefsdobta

DohwpeommAtrsoaccmo

sci2s7ccfoseoaThbcavms

po“wio

T

C

nd some symptomatology must be present prior to 7ears of age. Impairment from the symptoms shouldxist in two or more settings (eg, school and home),nd significant impairment should be evident in social,cademic, or occupational domains.DSM-IV-TR does not specify a lower limit of age

or diagnosis, and, as stated, requires symptoms prioro 7 years of age. Prospective studies indicate thateak age of onset of ADHD is between 3 and 4 yearsf age.26 In a referred sample of school-aged childrenith diagnosed ADHD, mothers reported that onset of

ymptoms occurred at or before the fourth birthday inwo-thirds of the children.27 Therefore, it is likely thathildren in the preschool age group, defined as 2hrough 5 years of age, will come to the attention oflinicians because of ADHD symptomatology. How-ver, less is known about the use of DSM-IV criteriaor diagnosis of ADHD in preschool children than inchool-age children.28 Since the DSM-IV criteria foriagnosis of ADHD are the same regardless of the agef the child, the developmental progression of normalehaviors and the differentiation of abnormal symp-oms from normal age-appropriate behaviors is not

ABLE 1. DSM-IV-TR symptoms of ADHD25

Symptoms of inattention (occurring often)

1. Fails to give close attention to details, makes carelessmistakes

2. Has difficulty sustaining attention3. Does not seem to listen when spoken to4. Does not follow through on instructions or finish schoolwork or

chores5. Has difficulty organizing tasks and activities6. Avoids or dislikes to engage in tasks that require sustained

mental effort (eg, schoolwork or homework)7. Loses things8. Distracted by extraneous stimuli9. Forgetful in daily activities

Symptoms of hyperactivity-impulsivity (occurring often)

Hyperactivity1. Fidgets with hands or feet or squirms in seat2. Leaves seat in classroom or in other situations where

expected to remain seated3. Often runs about or climbs excessively in situation where it is

inappropriate4. Difficulty playing quietly5. “On the go” or acts as if “driven by a motor”6. Talks excessively

Impulsivity7. Blurts out answers before questions completed8. Difficulty awaiting turn9. Interrupts or intrudes on others (eg, in conversations or

games)

ddressed in DSM-IV-TR. The only guidance given in a


SM-IV-TR concerning differentiating normal devel-pmentally appropriate behavior from abnormal be-avior is that the symptoms should be “inconsistentith developmental level” in order to be scoredositively.25 DSM-IV-TR states that it is “difficult tostablish this diagnosis in children younger than age 4r 5 years, because their characteristic behavior isuch more variable than that of older children anday include features that are similar to symptoms ofttention-Deficit/Hyperactivity Disorder.”25 It is left

o the clinician to determine whether the observed oreported behaviors (high activity level, short attentionpan, need for immediate gratification, impulsivity,pposition to parental request) are developmentallyppropriate for the young child or representative oflinical pathology. The potential inability of the clini-ian to appreciate that many of the DSM-IV symptomsay be normal for younger children could lead to

verdiagnosis of ADHD in this age group.Another concern about the use of DSM-IV in pre-

chool children is raised by the skewed distribution ofhildren who met the criteria for the hyperactive-mpulsive subtype in the DSM-IV field trials.29 Only4% of children categorized as hyperactive-impulsiveubtype were older than 6 years, whereas more than0% of children categorized as inattentive subtype orombined subtype were older than 6 years. Lahey andolleagues have suggested two possible explanationsor this skewed distribution,30 as follows: (1) Fewlder children are found with the hyperactive-impul-ive subtype because as children grow older theyxhibit more symptoms of inattention as the demandsn them for attention increase (increased schoolworknd homework, tasks requiring greater concentration).herefore younger children who were categorized asyperactive-impulsive may be categorized as com-ined subtype at older ages. (2) Younger childrenategorized as hyperactive-impulsive are inappropri-tely diagnosed as ADHD because they exhibit aariation of normal activity and exuberance. As theyature, they no longer meet the criteria for any

ubtype of ADHD.A third concern about using DSM-IV criteria inreschool children is the wording of the descriptionsf a number of the symptoms.31,32 Phrases such asfails to finish schoolwork, chores, or duties in theorkplace” and “often leaves seat in classroom” seem

nappropriate to describe the activities and behaviorsf preschool children. The lack of developmentally
ppropriate examples of behavior in the DSM-IV
9

cptia

RP

uddfbAadaq1

bcPSotRetrCctvs

thifhifbpcAA

rtotAStcfta

bcsDlehcm

issdctaara

opacAfp

PP

vw(T

1

riteria make the diagnosis of ADHD in preschoolersroblematic. The existing examples may be confusingo parents and teachers and lead to a lack of reliabilityn their reports. Even worse, they may lead to overdi-gnosis of ADHD in the preschool child.

eliability of ADHD-Specific Rating Scales inreschool Children

ADHD-specific rating scales are recommended forse in school-age children to aid the clinician iniagnosing and managing symptoms and impairmentue to ADHD.33 These rating scales come in separateorms for parent and teacher and have been shown toe reliable and to accurately distinguish children withDHD from children without ADHD in the school-

ge group.34 Most of these rating scales are now basedirectly on the 18 symptoms listed in the DSM-IV-TRnd include a Likert scale scoring system for fre-uency of symptoms from 0 to 3 (0 � never, seldom;� occasionally; 2 � often; 3 � very often).Several of the ADHD-specific rating scales haveeen shown to be reliable when used with preschoolhildren 3 years and older. These include the Connorsarent Rating Scale–Revised, the Connors Teachercale–Revised35,36 (validated on children 3 years andlder), and the AD/HD Rating Scale–IV parent andeacher versions.37 For example, the Conners’ Parentating Scale–Revised has been shown to have mod-rate to high test-retest reliability in diagnosing thehree ADHD subtypes with reliability coefficientsanging from 0.67 to 0.81 for the DSM-IV subscales.ronbach’s alpha coefficients, a measure of internalonsistency, have been measured for both parent andeacher versions of the Conners’ Rating Scales–Re-ised and range from 0.82 to 0.96 for the DSM-IVubscales.The Early Childhood Inventory-4 (ECI-4) parent and

eacher versions38,39 is also based on the DSM-IV andas subscales for ADHD inattention and hyperactive-mpulsive subtypes. The ECI-4 ADHD subscales, usedor children 3 to 5 years of age, have been shown toave moderate to high test-retest reliability in diagnos-ng the three ADHD subtypes with Pearson r’s rangingrom 0.64 to 0.72. Cronbach’s alpha coefficients haveeen measured for the ADHD subscales on both thearent and the teacher versions of the ECI-4 and areonsistently over 0.80. The ECI-4 subscales forDHD are the same as the ADHD subscales on the
DHD Symptom Checklist-440 and therefore this d
0

ating scale, specific to ADHD, can also be consideredo be reliable for children 3 to 5 years old. Severalther commonly used ADHD-specific rating scales,he Vanderbilt,41-43 which comes with the Americancademy of Pediatrics ADHD Toolkit,44 and theNAP-IV,45,46 have no reported psychometric data on

heir use with young children. Nevertheless, theirontent and structure are so similar to the rating scalesor which there is reliability data that it is likely thatheir use with preschool children would also be reli-ble.The Child Behavior Checklist for Ages 1½ to 5, aroad checklist for behavioral symptoms in younghildren, has two subscales that pertain to ADHDymptoms.4 The Attention Problems subscale and theSM-oriented Attention Deficit/Hyperactivity Prob-

ems subscale have reported test-retest reliability co-fficients ranging from 0.74 to 0.78. Since the CBCLas 100 items, only 6 of which pertain to ADHD, itannot be recommended for specific diagnosis oranagement of ADHD.The Preschool Age Psychiatric Assessment (PAPA)

s a structured parent interview assessing psychiatricymptoms and disorders in preschool children.47 Intudies of its test-retest reliability, the kappa for theiagnosis of ADHD was 0.74 and the intraclassorrelation coefficient for the test-retest reliability ofhe ADHD scale score was 0.80.48 The PAPA takespproximately 2.5 hours to perform and score, so it isppropriate for in-depth psychiatric diagnosis andesearch, but not for pediatric office screening orssessment of ADHD.In summary, ADHD-specific rating scales, subscalesn behavioral checklists, and structured psychiatricarent interviews have all been shown to be reliable inssessing preschool children for ADHD. Despite con-ern about applicability and wording of DSM-IVDHD symptom criteria for preschool children, tools

or the reliable measurement of ADHD symptoms inreschool children are available to the clinician.

revalence of ADHD in School-Aged andreschool Children

Prevalence rates of ADHD in school-aged childrenary in study samples from 4 to 12% (median 5.8%),ith prevalence rates higher in community samples

mean 10.3%) than in school samples (mean 6.9%).34

hese studies varied as to whether they required
ocumentation of impairment for the diagnosis of

AwDietpsuiott

As(alwrobawdrwdAaccikitpsdscosoiATid

airprtssbapNiWrDcIcnAqAprcssmrsple

st4sdCc6Dtlut

C

DHD, as indicated in DSM-IV. Most of these studiesere based on previous DSM criteria (DSM-III andSM-III-R), neither of which required documented

mpairment in social or academic functioning, orvidence of impairment in both school and home. Inhese school-aged samples, the male/female ratio ofrevalence is approximately 3:1. In a school-basedtudy of children in kindergarten through fifth gradesing teacher assessment (including a measure ofmpairment), Wolraich and colleagues found that 48%f the children with ADHD had the inattentive sub-ype, 43% had the combined subtype, and only 9% hadhe hyperactive-impulsive subtype.42

A high proportion of school-aged children withDHD have comorbid conditions, specifically oppo-

itional defiant disorder (ODD), conduct disorderCD), depressive and anxiety disorders. ODD involvespattern of negativistic, defiant, and hostile behavior

asting for at least 6 months. Children with ODD argueith adults, refuse to comply with adults’ requests or

ules, and are often angry, touchy, and annoying tothers.25 In contrast, CD is a persistent pattern ofehavior in which the basic rights of others andge-appropriate societal norms are violated. Childrenith CD may be aggressive to people and animals,estroy property, lie, and steal.25 Mean prevalenceates for these comorbidities in school-aged childrenith ADHD are highest for ODD (35%), with CD andepression occurring in about 25% of these children.nxiety disorders are least common, with mean prev-

lence rate of 18%.34 In a recent survey of Britishhildren and adolescents, 53% with ADHD had aomorbidity of another disruptive behavior disorder,ncluding 27% with ODD, and 18% with CD.49 Less isnown about prevalence rates for co-occurring learn-ng disabilities or learning problems, although much ofhe impairment in school-aged children is related tooor academic performance. In a school-basedtudy,50 over 60% of children with ADHD had aca-emic problems, with a differential pattern amongubtypes. Almost 75% of children with inattentive orombined subtypes had academic problems, whilenly 23% of children with the hyperactive-impulsiveubtype had academic problems. However, diagnosisf a separate, but comorbid, learning disability (versusdentification of learning problems directly related toDHD symptoms and behaviors) is often difficult.here is also the problem of definition. Perhaps

nattentive symptoms of ADHD are a specific learning
isability, albeit not defined in the DSM-IV-TR. s

In the last 10 years, a number of studies havettempted to address the issue of prevalence of ADHDn US preschool children. Studies that come fromeferral or psychiatric clinic populations reflect sam-ling biases and cannot provide valid estimates ofates of ADHD in the general population. This review,herefore, only considers studies that have community,chool, or primary care samples.40,48,51-54 Table 2ummarizes the results of these studies. All studies areased on parent report, not parent and teacher report,nd therefore do not necessarily address finding im-airment due to symptoms in at least two settings.one of the studies using symptom checklists assess

mpairment in social, academic, or family functioning.e know that when a measure of impairment is

equired for the diagnosis of ADHD, in addition toSM-IV symptom criteria as measured by a symptom

hecklist, reported prevalence rates drop substantially.n the study of school children by Wolraich andolleagues, when DSM-IV impairment criteria wereot considered, 16% of the sample was diagnosed withDHD. When DSM-IV impairment criteria were re-uired for diagnosis of ADHD, overall prevalence ofDHD dropped to 6.8%.42 Several of the studies ofreschool prevalence also have substantial refusalates or uncontrolled selection of patients, raising theoncern of selection bias. Finally, none of the checklisttudies, nor DSM-III-R-based studies, require thatymptoms are long lasting (ie, at least for the last 6onths). All of these factors (the lack of teacher

eport, the lack of DSM-IV impairment criteria inome studies, the potential for selection bias, and theotential for mistakenly diagnosing a transient prob-em as a chronic disorder) may lead to falsely elevatedstimates of prevalence rates.The overall prevalence rate of the ADHD in these

tudies of preschool children, calculated by weightinghe rates in individual studies by sample size, was.9% (see Table 2). However, considering only thosetudies that required a measure of impairment foriagnosis decreases the prevalence rate to 2.8%.48,51,52

onsidering only those studies that used DSM-IVriteria for diagnosis increases the prevalence rate to.3%.40,48,53,54 It is possible that studies usingSM-IV criteria, with a separate subtype for hyperac-

ive-impulsive symptoms, may lead to higher preva-ence rates in preschool children than those studiessing DSM-III-R criteria. In the DSM-IV field trials,here was a 15% increase in diagnosis of ADHD, all
ubtypes and all ages, when using DSM-IV criteria
11

caatboibnLtilp(

diatvmctc

fic

stsgiotcrad

T

L

G

K

G

G

E

W

a

b

c

d

e

f d ini

Tc

IHC

a

cb

1

ompared to previous DSM criteria.29 There was alson increase in diagnosis of children in the preschoolge group, primarily due to diagnosis of the hyperac-ive-impulsive subtype. However, all of the DSM-IV-ased prevalence studies listed in Table 2 except forne48 used symptom checklists and thus did notnclude a measure of impairment. The one DSM-IV-ased study that did require impairment for the diag-osis of ADHD found a prevalence rate of 3.3%.48

ack of measurement of impairment, therefore, seemso be the major factor causing higher prevalence ratesn the DSM-IV group of studies. The overall preva-ence rate of 4.9% (2.8 to 6.3%) is similar to therevalence rates found for US school-aged children5.8%).As mentioned at the beginning of this section, theistribution of ADHD subtypes in preschool childrens markedly different from the distribution in school-ged children (Table 3). The prevalence of the inat-entive and hyperactive-impulsive subtypes is re-ersed, with few children in the preschool age groupeeting criteria for the inattentive subtype and few

hildren in the school-aged group meeting criteria forhe hyperactive-impulsive subtype. These data are

ABLE 2. Prevalence of preschool ADHD (parent as informant)

Study MeasureImpairmentmeasured?

Child(y

avigne et al(1996)51

Consensus evaluation(two psychologists);DSM-III-R

Yes 2

adow andSprafkin(1997)40

DSM-IV checklist(ADHD subscales)a

No 3

eenan et al(1997)52

Structured DiagnosticDSM-III-R Interview(K-SADS)b

Yes 4.6

impel andKuhn(2000)53

DSM-IV checklist forADHDc

No 2

adow et al(2001)54

DSM-IV checklist(ADHD subscales)a

No 3

gger et al (inpress)48

Structured DiagnosticDSM-IV Interview(PAPA)d

Yes 2

eighted average prevalencee

Early Childhood Inventory-4 (ECI-4).38

Kiddie-Schedule for Affective Disorders and Schizophrenia.55

AD/HD Rating Scale-1.37

Preschool Age Psychiatric Assessment.47

In each subtype and in total ADHD prevalence, all applicable studies were usIf only studies with clinical diagnostic methods/impairment measures includencluded in analysis, total ADHD prevalence � 6.3%.

onsistent with the findings in the original DSM-IV A

2

eld trials29 and with results of studies of preschoolhildren based on teacher, not parent, report.56

Despite the reversal of the prevalence of these twoubtypes from the preschool to the school-age periods,he similar total prevalence of ADHD among pre-chool children as compared to school-aged children isenerally reassuring. If the DSM-IV criteria werenvalid for use with preschool children and led toverdiagnosis of ADHD (primarily due to the inabilityo differentiate normal activity and lack of impulseontrol in this age group from pathology), prevalenceates in preschool children would be falsely elevatednd would be higher than those in school-aged chil-ren. In view of the reported prevalence rates of

eRatio

boys/girlswith ADHD

ADHD-I(%)

ADHD-HI (%)

ADHD-combined

(%)

ADHDtotal(%)

2:1 N/A N/A N/A 2.0

1.5:1 0.0 3.1 2.5 5.7

N/A N/A N/A N/A 5.7

2:1 2.0 3.6 4.0 9.5

2:1 0.9 3.6 1.5 6.0

2.5:1 0.0 1.8 1.5 3.3

0.8 3.1 2.4 4.9f

weighted average calculation.analysis, total ADHD prevalence � 2.8%. If only studies with DSM-IV criteria

ABLE 3. Comparison of ADHD subtypes in preschool and school-agedhildren

ADHD subtypePreschool (% total

prevalence)aSchool-aged (% of total

prevalence)b

nattentive 13 48yperactive-impulsive 49 9ombined 38 43

Based on weighted average prevalence in studies of ADHD in preschoolhildren (see Table 1).Wolraich et al 1998.42

’s agrs)

–5

–5

–5.8

–6

–5

–5

ed in

DHD in preschool children, it is, therefore, less


lndatahtsAaAeytcmtdn

proseagctght

C

sbfAOipApAChnc

eoes

AswlscTwOsAcsstNOAhc

lssoptoO

VA

cotAiAHctp

C

ikely that the reversal of subtypes is due to overdiag-osis, and more likely that other factors explain theseifferences. One explanation is that offered by Laheynd colleagues.30 As noted previously, they suggestedhat, as children get older, the increased demands forttention would change their categorization from theyperactive-impulsive subtype to the combined sub-ype. Egger and colleague’s finding that the combinedubtype is nonexistent in 2-year-olds diagnosed withDHD, and its prevalence increases dramatically from

ge 3 to 5, is consistent with this hypothesis.48

nother possible explanation for the observed differ-nces in subtype prevalence is that while some of theounger children who were categorized as hyperac-ive-impulsive as young children no longer meetriteria for hyperactive-impulsive behavior as theyature, they now exhibit symptoms of inattention as

he demands for attention increase. Their attentionalifficulties become apparent and more easily diag-osed.Gender differences in preschool children seem lessronounced than in older children. In contrast to a 3:1atio of boys to girls in school-aged children, the ratiof boys to girls diagnosed with ADHD in the pre-chool age group is 2:1 (see Table 2). Gender differ-nces among ADHD subtypes in preschool childrenre less clear. One study reported an almost 10-foldreater prevalence of the combined subtype in boys asompared to girls.48 Other studies found no differen-ial prevalence rates among the three subtypes due toender, with boys consistently exhibiting somewhatigher prevalence of ADHD symptoms among allhree ADHD subtypes.53,54

ommon Comorbidities in Preschool ADHD

Similar to school-aged children with ADHD, pre-chool children with ADHD are likely to have comor-id behavioral disorders. Lavigne and colleaguesound that the majority (87%) of preschoolers withDHD had comorbid disorders, almost alwaysDD.51 Gadow and colleagues reported that approx-

mately half of preschool children in a community andrimary care sample who met DSM-IV cutoffs forDHD symptoms had comorbid ODD.54 Eggers re-orts that over half (55%) of preschool children withDHD have one or more comorbidities: 39% haveD, 36% have ODD, 13% have depression, and 15%ave anxiety disorders.57 Multiple comorbidities wereot uncommon, with 19% of children having two
omorbidities and 12% having three morbidities. Egg- A

rs found a significant association of ADHD with allf these comorbidities except anxiety disorders; anxi-ty disorders were diagnosed in approximately theame number of children with or without ADHD.Preschool children with the combined subtype ofDHD are more likely to have comorbid ODD. In a

tudy of Swedish children 3 to 7 years of age, childrenith combined subtype ADHD were four times as

ikely to have ODD as children with the inattentiveubtype and twice as likely to have comorbid ODD ashildren with the hyperactive-impulsive subtype.58

hus comorbidity with ODD is not only associatedith more symptomatology due to the addition ofDD symptoms but is likely to be a marker for more

evere ADHD symptomatology as well. In additionDHD children with comorbid ODD were signifi-

antly more likely to be anxious or depressed. Thistudy also documented the high prevalence of ODDymptoms in young children with ADHD, even whenhey did not meet all criteria for comorbid ODD.inety-two percent of the ADHD children withoutDD had at least one ODD symptom. Furthermore,DHD children without ODD scored significantlyigher on an ODD rating scale than comparisonhildren without ADHD.In summary, preschool children with ADHD are

ikely to have comorbidities, especially ODD. In alltudies looking at preschool children, at least halfuffered from a comorbid condition. In approximatelyne-third of cases, two or more comorbidities areresent. The addition of the diagnosis of ODD is likelyo be a marker for more severe ADHD symptomatol-gy. Even those children without the diagnosis ofDD are likely to have some oppositional behaviors.

alidity of DSM-IV Criteria for Diagnosis ofDHD in Preschool Children

The studies of the prevalence of ADHD in preschoolhildren (which show rates similar to prevalence ratesf ADHD in school-aged children) appear to indicatehat using DSM-IV criteria leads to the diagnosis ofDHD in a small group of young children in need of

ntervention and does not lead to the overdiagnosis ofDHD in normally active, rambunctious preschoolers.owever, if preschool children are in fact being

orrectly identified with ADHD by DSM-IV criteria,hen those children should have strong evidence ofsychosocial and academic impairment typical of
DHD. There should also be some evidence of a
13

“iFsimsdndfsAisstr

scsrigAcafsoaAutsAltarciegctrrg

iuttsaichcoawsmCaptr

ssawlssdfita

swtlacctRltrAst

1

dose effect”; that is, as severity of symptomatologyncreases, severity of impairment should also increase.urthermore, since ADHD is a chronic disease, therehould be evidence of stability of both symptoms andmpairment over time. As these children get older andove into the school-age period, they should remain

ymptomatic and impaired, and continue with theiagnosis of ADHD. Finally, the same underlyingeuropsychological deficits found in school-aged chil-ren with ADHD, such as difficulties with executiveunctioning, delay aversion, and inhibitory control,hould be found in preschool children diagnosed withDHD. A number of studies have evaluated these

ssues: psychosocial and academic impairment in pre-chool children with ADHD; dose effect of ADHDymptoms on impairment; stability of ADHD symp-oms, impairment, and diagnosis over time; and neu-opsychological profile of preschool ADHD.Psychosocial and Academic Impairment in Pre-

chool Children with ADHD. Lahey and colleaguesompared 4- to 6-year-old children with DSM-IVymptom criteria for ADHD to a group of childrenecruited from the same or nearby schools.30 Compar-son children were matched to the ADHD cohort onender, ethnicity, age, and socioeconomic status.nalyses controlled for age, gender, intelligence, so-

ioeconomic status, and comorbidities (ODD, CD,nxiety, and depression). Each subtype of ADHD wasound to be associated with functional impairment inocial and academic skills. This was true for the resultsf teacher, parent, and self-assessments of functioning,s well as standardized testing. Children with allDHD subtypes were rated as significantly less pop-lar with classmates than the comparison children, andhose children who met criteria for the combinedubtype were actively disliked. All children withDHD were perceived by teachers to be significantly

ess prosocial, less cooperative, and less assertive thanhose in the comparison group. Children in the hyper-ctive-impulsive and combined subtypes were alsoated as significantly more disruptive and less self-ontrolled than children in the comparison group. Ofnterest, the investigators also found that children inach of the ADHD subtypes reported significantlyreater problems in friendships than children in theomparison group, corroborating the impression ofheir teachers. In addition, parents and interviewersated children in each ADHD subtype lower on globalatings of adaptive functioning than the comparison
roup. h
4

In this study, parents of children in the hyperactive-mpulsive subtype also reported significantly morenintentional injuries caused by the child’s behaviorhan parents of comparison children. There was a trendoward greater unintentional injuries in the combinedubtype. For example 36% of children with the hyper-ctive-impulsive ADHD subtype had experienced un-ntentional injuries as compared to 12% of non-ADHDhildren. Children with ADHD were also found toave greater academic difficulties than children in theomparison group. Depending on subtype, 15 to 25%f the children with ADHD were in special educations compared to 0% of non-ADHD children. Childrenho met criteria for the combined or inattentive

ubtypes had significantly lower mathematics achieve-ent relative to intelligence than comparison children.hildren in the hyperactive-impulsive subtype showedtrend toward lower mathematics scores than com-

arison children. Furthermore, children with the inat-entive subtype trended toward underachievement ineading compared to non-ADHD children.In summary, preschool children with all ADHD

ubtypes were found to be significantly impaired inocial and academic functioning. Similar to school-ged children with ADHD,42,50 preschool childrenith combined and inattentive subtypes were more

ikely to experience academic difficulties, and pre-chool children with combined and hyperactive-impul-ive subtypes were more likely to be consideredisruptive and lacking self-control. Of interest was thending of the additional morbidity of increased unin-

entional injuries in preschool children with the hyper-ctive-impulsive subtype of ADHD.Egger and colleagues also found significant psycho-

ocial and academic impairment in preschool childrenith ADHD.48 Preschool children with ADHD, in

heir study of 2- to 5-year-olds, were eight times moreikely to show significant impairment in relationshipsnd functioning in the home and in school thanhildren without ADHD. For example 71% of thehildren with ADHD had impaired relationships withheir parents versus 12% of non-ADHD preschoolers.atios of impaired relationships with teachers, sib-

ings, and peers for ADHD preschool children versushose without ADHD were 43:4, 41:10, and 50:6%,espectively. Overall, 89% of preschool children withDHD had significant impairment in at least one

ocial relationship.57 Children with the combined sub-ype were more impaired than children with the
yperactive-impulsive subtype (no children with the

iccbtiwsAa6wdshh

Dwpapssg4gtwanpspstaldeedaldo

A(i

Lsnaalriptaalcipirsdmdrgpogttadlamtioehs(radmllcg

C

nattentive subtype were identified), and children withomorbidities such as ODD were more impaired thanhildren with ADHD alone. Impairment was found inoth home and preschool or daycare. More than half ofhe parents expressed serious concerns about manag-ng their child’s behavior and reported that it interferedith family activities (such as taking the child to a

tore or restaurant). Mothers reported that 58% of theDHD diagnosed preschool children were unable to

ct appropriately in public places, as compared with% of non-ADHD children. Over 40% of the childrenith ADHD had been suspended from school oraycare compared to 0.6% of the non-ADHD pre-choolers. Almost 16% of the children with ADHDad been expelled. All of those who had been expelledad the combined subtype with comorbidities.In a study of 94 middle-class 3- to 5-year-olds,uPaul and colleagues found that preschool childrenith ADHD exhibited significantly more behaviorroblems and were significantly less socially skilledccording to behavior ratings by their teachers andarents.59 These differences were large, with effectizes for differences of behavior problems and socialkills between ADHD and non-ADHD childrenreater than 1.0 and frequently in the range of 2.0 to.0. Effect sizes are mean differences between theroups in standard deviation units. During observa-ions of parent–child interactions, ADHD childrenere more frequently noncompliant and inappropriate

nd their parents were more likely to respond withegative behavior toward their children. Parents ofreschoolers with ADHD experienced high levels oftress and were coping less adaptively compared toarents of non-ADHD preschoolers. The ADHD pre-chool children also scored significantly lower on aest of developmental and pre-academic skills. Onverage, the ADHD group scored 1 standard deviationower on reasoning, academic skills, and conceptevelopment than the comparison group or than thexpected mean for their age. Thus, ADHD preschool-rs exhibit impairment in social skills and pre-aca-emic skills, and their relationships with their parentsre negatively affected by their behavior. Their fami-ies are more stressed and experience greater familyysfunction than families of preschool children with-ut ADHD.There is also some evidence that young children withDHD, especially those with inattentive symptoms

eg, combined and inattentive subtypes), have deficits
n language development and emergent literacy skills. l

onigan and colleagues found significant, unique as-ociations between inattention measured by the Con-ers’ Teacher Rating Scale and language developmentnd phonological processing abilities.60 This associ-ted impairment is an important one, since earlyanguage and emergent literacy skills are predictive ofeading abilities in school.61 Understanding causalityn this association is complex. One hypothetical causalathway is that behavior problems, especially inatten-ion, interfere with language development and thettainment of reading skills.62 According to the trans-ctional model of language acquisition, children learnanguage through interaction with their parents. If thehild’s inattentive (or hyperactive-impulsive) behaviornterferes with joint attention activities, parental ex-ansion and extension of the child’s language may beneffective. Similarly, if the child is inattentive toeading aloud activities, acquisition of prereadingkills and beginning phonological processing may beisrupted. The child’s behavior may also lead theother to abandon language or reading activities. This

irection of this causal pathway is supported byesearch that shows that attention problems in kinder-arten predict later reading difficulty, whereas earlyoor reading did not predict later inattention.63 An-ther possibility is that the process of learning lan-uage, in which the parent directs the child’s attentiono conversations, objects, and concepts, is important inhe development of memory, executive processing,nd self-regulation.64 If this process does not occurue to parental dysfunction or the child’s innateanguage problems, then the development of attentionnd executive functioning may be impaired. Further-ore, poor language skills and other learning difficul-

ies may frustrate the preschool child, leading tonattentive, hyperactive, and disruptive behaviors. Inne study of low socioeconomic status preschool boys,mergent reading skills, attention, and disruptive be-aviors were measured.65 Path analysis in this sampleeemed to indicate that poor emergent reading skillseg, receptive and expressive language and letterecognition) may make it difficult for the child to payttention in the classroom and secondarily lead toisruptive behavior. Of course, the causal pathwaysay be bidirectional. Problems with attention may

ead to poor language and pre-academic skills; pooranguage and pre-academic skills may worsen diffi-ulties with attention and behavior. Finally, commonenetic influences may cause both inattention and
anguage/reading difficulties, leading to their associa-
15

tei

Pwerthtspwtssltbthmdsencmt

fbmhie3aicsi

DIAct

it

sC3atDaTeoa

fIisltch

iitwipetameafsar

oAarAsoc

1

ion as comorbidities.66 Further research is needed tolucidate which of these causal pathways is mostmportant.Dose Effect of ADHD Symptoms on Impairment inreschool Children. DSM-IV criteria were developedith strict cutoffs for diagnosis, with a requirement for

ach of the subtypes of six or more symptoms occur-ing “often.”25 The behaviors of inattention, hyperac-ivity, and impulsivity that parents and teachers report,owever, appear to follow a normal distribution ratherhan a bimodal one.67 The cutoff of six or moreymptoms in the DSM-IV was somewhat arbitrary andartly based on being conservative in labeling childrenith ADHD, as well as opting for consistency among

he number of symptoms required for each of theubtypes.29 In addition, some of the ADHD checklistcales use normative data and define ADHD as scoresying greater than 1.5 or 2 standard deviations abovehe mean.36 It is therefore difficult to draw the lineetween normality and disorder. The DSM-IV fieldrials found a linear relationship between number ofyperactive-impulsive symptoms and impairment aseasured by the children’s global assessment scale,

emonstrating a “dose effect” between number ofymptoms and level of impairment.29 One wouldxpect, therefore, that a dose effect for increasingumber of symptoms causing increasing impairmentould be demonstrated in preschool children, if theeasurement of symptoms by DSM-IV criteria in

hose children is valid.In the PAPA test-retest study, a dose effect was, in

act, demonstrated.48 A linear relationship was foundetween number of symptoms and level of impair-ent. For each additional inattentive symptom or

yperactive symptom, the child’s probability of beingmpaired nearly doubled with an odds ratio of 1.7. Forxample, with three hyperactive impulsive symptoms,1% of the children were impaired; with four hyper-ctive-impulsive symptoms, 57% of children werempaired.57 This demonstrated dose effect supports theonstruct validity of ADHD in preschool children,ince it is consistent with our understanding of ADHDn school-aged children.Stability of ADHD Symptoms, Impairment, andiagnosis from the Preschool to School-Age Period.

t is particularly important to evaluate the stability ofDHD symptomatology and impairment in preschool

hildren. The thorny issues of behavioral and drug
reatment for these children make it essential to know S
6

f these symptoms and impairment persist or areransient.Several studies have looked at the persistence of

ymptoms of hyperactivity as reported by mothers.ampbell and colleagues identified a cohort of 2- to-year-olds with problem behaviors including hyper-ctivity and difficult management by mothers andeachers. At follow-up at age 6, about one-third metSM-III criteria with attention deficit disorder (ADD),

nd 50% had ADD, aggressive behavior, or both.68

wo-thirds of the children diagnosed with a DSM-IIIxternalizing disorder (ADD, ODD, or CD) at 6 yearsf age persisted with a DSM-III externalizing disordert age 9.69

Similar results were found in another long-termollow-up study of hyperactive preschool children.70

n this study, the preschoolers with hyperactivity weredentified as having greater impairments in languagekills than comparison children. Over a 12-year fol-ow-up period, they persisted in having poorer cogni-ive skills, lower levels of reading ability, as well asontinued disruptive and inattentive behaviors andigher rates of DSM-III disorders.In a third study, investigators followed an econom-

cally disadvantaged group of 4.5- to 5-year-oldsdentified as “acting out” in preschool through thehird grade. Eighty percent of the acting out childrenere considered to have persistent behavior problems

n at least two of three grades.71 In addition toersistent behavior problems, the acting out preschool-rs had significantly lower academic achievement inhe primary grades and were viewed by their teacherss more impaired in peer relationships and in adjust-ent to school than comparison children. The home

nvironment, especially degree of stimulation, predict-bility, and organization, was a strong protectiveactor, and measures of the home environment wereignificantly higher in the comparison group, as wells in those children in the acting out group whoeverted to normal behavior during the primary grades.There is only one study that looks at the persistencef impairment in preschool children diagnosed withDHD by DSM-IV criteria.72 Children 4 to 6 years of

ge were followed for three consecutive years ande-evaluated yearly. Ninety-six children had DSM-IVDHD (full ADHD group); 29 children had DSM-IV

ymptom criteria for ADHD but met criteria only inne setting (“situational” ADHD group), and 130hildren were without ADHD (comparison group).
eventy-nine percent of the full ADHD group met full

d3sgtmfcmcgmwotpiAwytgelg

pcssmayfnss

Asd“snfsplia

ugaritdt

sasrbibgyefac

iCntaaisp

asTs

TWA

vvpri

C

iagnostic criteria for ADHD at least twice during the-year follow-up period. In contrast, 35% of theituational ADHD group and 3% of the comparisonroup met full diagnostic criteria at least twice duringhe follow-up period. Social and academic impair-ents, documented at diagnosis, also persisted during

ollow-up. The full ADHD group exhibited signifi-antly greater social, academic, and global impair-ents during the 3 years of follow-up than the

omparison children, with the situational ADHDroup experiencing an intermediate level of impair-ent. The stability of impairment was impressive,ith kappas in the range of 0.50 to 0.79 for agreementf significant impairment in the home, in peer rela-ions, in school, and for academic problems and socialreference. Global impairment ratings by parents andnterviewers were equally stable. Over 30% of the fullDHD group and 25% of the situational ADHD groupere placed in special education in at least 1 of the 3ears of follow-up, as compared to less than 10% ofhe comparison group. Over 60% of the full ADHDroup and over 50% of the situational ADHD groupxperienced an unintentional injury during the fol-ow-up period, as compared to 16% of the comparisonroup.In summary, ADHD diagnosed in the preschooleriod persists with remarkable stability and is asso-iated with significant and persistent impairment inocial and academic functioning into the elementarychool grades. Preschool children identified as “nor-al” also remain remarkably stable and continue to be

symptomatic and unimpaired over a period of 3ears. Of interest, preschool children who do not meetull DSM-IV criteria for ADHD, but who show sig-ificant ADHD symptomatology, also continue tohow significant impairment into the elementarychool grades.The Neuropsychological Profile of PreschoolDHD. School-aged children with ADHD have been

hown to demonstrate a variety of neuropsychologicaleficits. Most of these deficits are categorized asexecutive functions” associated with the frontal-triatal circuits implicated in the changes seen ineuroimaging of children with ADHD.73 Executiveunctions are a set of brain functions including re-ponse inhibition, cognitive flexibility or set shifting,lanning, and working memory. These neuropsycho-ogical processes have been shown to be generallympaired in school-aged children with ADHD.74,75 In
ddition, ADHD school-aged children appear to be m

nwilling to delay their need for gratification, andiven a choice between a small immediate reward andlarge delayed reward, they choose the immediate

eward.76,77 While some of these deficits can be seenn children with other diagnoses (such as high func-ioning autism and ODD),78 executive dysfunction andelay aversion are neuropsychological characteristicshat are consistent with the diagnosis of ADHD.Sonuga-Barke and colleagues tested a community

ample of 156 children between 3 and 5.5 years of agend diagnosed a subgroup with ADHD through atructured clinical interview based on DSM-IV crite-ia.79 All children were given an age-appropriateattery of tests measuring executive functions (includ-ng working memory, set shifting or cognitive flexi-ility, and planning) as well as measuring delay ofratification and preference for delayed rewards. Anal-sis of test results revealed two significant factors:xecutive dysfunction and delay aversion. Both theseactors were predictive of the ADHD symptoms, evenfter controlling for IQ, age, and the presence ofonduct problems.Hughes and colleagues studied executive function-

ng in a group of children 3 to 5 years of age.80

hildren with ADHD-like symptoms were not diag-osed with strict DSM-IV criteria, but were rated byheir mothers as above the 90th percentile for hyper-ctivity on a strengths and weaknesses questionnairend were compared to a group of children who scoredn the normal range. The hyperactive preschoolerscored significantly lower on tests of working memory,lanning, inhibitory control, and cognitive flexibility.The results of these studies indicate that preschool

nd school-aged children with the diagnosis of ADHDhare similar neuropsychological characteristics.hese studies provide additional support for the con-truct validity of preschool ADHD.

reatmenthat We Know About the Treatment of

DHD in School-Aged Children

Treatment of ADHD in school-aged children in-olves use of psychostimulants and behavioral inter-entions. Behavioral interventions have focused onarent training, behavioral modifications in the class-oom, or both. Efficacy of both psychostimulant med-cation81 and behavioral therapy82 has been shown in

ultiple studies.

17

edDtsaastctiii0nidrtamwmstcsgdinmcscbamcdm

tsAtAb

cnmevMwwmcwcs

ttiosthsecsetmwspa

CM

gotrliMlscmp

1

While most of the studies have looked at short-termfficacy, the NIMH Collaborative Multisite Multimo-al Treatment Study of Children With Attention-eficit/Hyperactivity Disorder (MTA) looked at these

reatments with endpoints at 14 months.83,84 The MTAtudy compared almost 600 children, ages 7 to 9 years,ssigned to one of four treatments: medication man-gement, behavior modification (home, school, andummer camp), a combined behavioral and medicationreatment group, and a routine community treatmentomparison. For ADHD symptoms, both the medica-ion management and the combined treatment groupsmproved significantly more than the behavioral mod-fication or community groups. Effect size (ES) of themprovement was large, equivalent to approximately.60 standard deviation units. For ADHD symptoms,o significant advantage was found for adding behav-oral modification to medication therapy. For otheromains of functions (oppositional behaviors, peerelationships, social skills, and reading achievement),he combination of behavioral and medication man-gement was slightly superior to medication manage-ent or behavior management alone.83,84 In addition,hen looking at overall or global improvement acrossultiple domains and sites, combined treatment

howed modest significant advantages over medica-ion management (ES � 0.26).46 Another advantage ofombination treatment was the need for lower doses oftimulant medication compared with the medicationroup. For those children with comorbid anxietyisorders, and for low socioeconomic families, behav-oral treatment was significantly better than commu-ity care and had similar efficacy to combined andedication management.83,84 A follow-up of these

hildren at 24 months, 10 months after the end of thetudy, revealed a persistence of superiority of theombined and medication management group over theehavioral modification and community groups, albeitt a reduced ES (50% of ES at the end of 14onths).85,86 Of some concern, those children most

onsistently on medications showed significantly re-uced height gain compared with those children not onedication.In summary, the results of the MTA study indicated

he long-term efficacy and effectiveness of psycho-timulant medication for the core symptoms ofDHD, and added benefit of intensive behavioral

herapy at home and in school for improving non-HDH domains of functioning. Behavior modification
y itself was not shown to be better than community i
8

are. However, the results of the MTA study shouldot be construed as proving that behavioral manage-ent is ineffective. Results related to the lack of

fficacy of unitary behavioral management must beiewed within the context of the limitations of theTA study. Most children in the community sampleere taking medication, so behavioral managementas being compared to another treatment (communityedication management), not to no treatment or pla-

ebo. When children with behavioral managementere compared to the unmedicated children in the

ommunity, they had superior reduction in ADHDymptoms.84

Unfortunately, although the MTA was longer termhan most other studies, it did not address true long-erm effectiveness. The important questions concern-ng effectiveness in improving education and socialutcomes by adulthood, without significant long-termide effects, remain to be answered. In addition, bothypes of treatment, medication management and be-avioral modification, were far more intensive thanervices generally available to most families. Forxample, the behavioral management component in-luded 27 group and 8 individual parent-trainingessions, an 8-week therapeutic summer camp experi-nce for each child, 10 to 16 biweekly sessions ofeacher consultations concerning behavior manage-ent, and 12 weeks of a behaviorally trained aideorking directly with the child.83 How results from

uch an intensive behavior medication regimen com-are to results of behavior therapy likely to be avail-ble to families in most communities is unknown.

oncerns About Use of Psychostimulantedication in Preschool Children

A population-based analysis of state Medicaid pro-ram data by Zito and colleagues revealed that 1.2%f 2- to 4-year-olds were receiving stimulant medica-ions in 1995. More than 2% of 4-year-olds wereeceiving methylphenidate and prescriptions of stimu-ant medications to preschoolers increased 2- to 3-foldn the from 1991 to 1995.87 In another study of state

edicaid data, over half of children 3 years of age oress with the diagnosis of ADHD were receivingtimulant medications, and one-third of these younghildren were receiving two or more psychotropicedications.88 Concerns about this extensive use of

sychostimulants in very young children were raised
n the academic community89-91 and by the public.

cptnMimlocscrdeeubofrtc

ActdndcdgitifoisfwAbwuTca

fpsa

mmtdalya

ET

tt4i3atdnictcslticc

smataostTes

C

Effect on Neurodevelopment. Most of these con-erns were focused on dangers to a changing and verylastic nervous system and the potential for alteringhe course of neurodevelopment. Studies on rats haveot been reassuring. In a study in prepubertal rats byoll and colleagues, density of dopamine transporters

n the striatum was significantly reduced after earlyethylphenidate administration.92 The decline was

ong-lasting and reached 50% by adulthood. Severalther studies in rats given methylphenidate also showhanges in the function of brain dopamine cells. Thesetudies also indicate that exposure to methylphenidateauses changes in behavior including alteration ofesponses to cocaine when the rat reaches adulthood,epressive-like symptoms, and anxiety.93-95 Thusarly exposure to psychostimulants may have delayedffects on anatomy and behavior that are not obviousntil adolescence or adulthood. These effects appear toe more extensive and permanent than when exposureccurs at older ages.96 While one cannot extrapolaterom rats to humans directly, and while animal studiesaise concerns about the use of psychostimulantshroughout childhood, these studies raise most seriousoncerns about use in very young children.Effect on Linear Growth. The relationship ofDHD to linear growth is complex. The disorder itself

ould be associated with altered central nervous sys-em growth factors, or with increased caloric expen-itures. Psychostimulant drugs may have direct centralervous system effects on growth factors or couldecrease linear growth through decreased appetite andaloric intake. It has been long recognized that chil-ren with ADHD on psychostimulants have slowedrowth over 1 to 2 years.97,98 Several studies havendicated that when medication is stopped, eitheremporarily on “drug holidays,” or permanently, theres growth rebound.99 Klein and colleagues ultimatelyound no significant decrease in final height in a cohortf ADHD children followed through adolescence andnto young adulthood.100,101 Spencer and colleaguestudied children and adolescents with ADHD andound an approximately 2-cm height deficit in thoseith ADHD.102 They also found that 10% of theDHD group were more than 2 standard deviationselow the average height for age. The height deficitsere only evident in early adolescence and seemednrelated to psychostimulant treatment or weight loss.he authors postulated that the deficits were due toatecholamine dysregulation in children with ADHD,
nd not due to psychostimulants. The MTA study t

ound growth suppression directly related to use ofsychostimulants, implying that lower growth rateseen in children with ADHD are due to medication usend not to their disorder.86

In summary, children with ADHD seem to haveodest deficits in linear growth. While these deficitsay be related to the disorder itself, there is evidence

hat psychostimulant use causes at least temporaryeficits in linear growth. There are no studies lookingt linear growth in young children on psychostimu-ants. However, the more rapid growth rate of theoung child raises concerns about growth suppressiont such a young age.

fficacy and Safety of Psychostimulants in thereatment of Preschool Children with ADHD

There have been 10 double-blind placebo controlledrials looking at efficacy of methylphenidate in thereatment of preschool children with ADHD (Table).103-112 Very few children below 4 years of age werencluded in the studies, and almost none were less than

years of age. There are no controlled trials ofmphetamines, long-acting stimulants, or pemoline inhe preschool age group, nor are there any publishedata on the efficacy or safety of atomoxetine, aonstimulant selective norepinephrine reuptake inhib-tor approved by the FDA for treatment of ADHD inhildren 6 years of age and older. As compared torials of psychostimulants in older children, adoles-ents, and adults, which numbered 150 in 1996,81 thismall number of studies on preschool children gives usimited information concerning efficacy and safety ofhese drugs. The total number of children with ADHDn all 10 studies of preschool children was 246,ompared to over 5000 school-aged children, adoles-ents, and adults in studies in those age groups.81

Efficacy. Table 4 summarizes the results of thesetudies. All but one106 of the studies found thatethylphenidate was statistically superior to placebo,

lthough outcome measures were varied. Only three ofhe studies used DSM-IV criteria to diagnose ADHD,nd only one used DSM-IV symptomatology as anutcome measure. A number of the studies had verymall numbers of subjects. Trials were of short dura-ion, with most studies lasting only several weeks.herefore these studies do not elucidate the long-termffectiveness or safety of psychostimulants in pre-chool children, even if the MTA definition of “long-
erm,” 14 months, is used. When effect sizes of
19

T

C

S

C

B

B

M

M

2

ABLE 4. Double-blind placebo-controlled trials of methylphenidate in preschool children with ADHD symptoms

StudyNo. preschool

subjectsAge (months)

Diagnosticcriteria

Duration andstudy design

MPHa dose Results: efficacy and side effects

onners,1975107

59 �72;Mean � 58

Hyperactiveandimpulsivesymptoms(maternalcomplaint)

42 days on drugor placebo(randomizedcontrolled trial)

Average dose12 mg/day; 0.75mg/kg bid

Efficacy: improvement in hyperactive-impulsive symptoms based onphysician and mother assessment;improvement on intelligence andvisual-motor tests

Side effects: minimalchleifer et al,1975111

26 40–58;Mean � 49

Hyperactiveandaggressivebypsychiatricinterview ofmother

42 days (21 dayson meds, 21days off inrandomizedcrossoverdesign)

Average dose5 mg bid,range 2.5to 30 mgper day

Efficacy: improvement in hyperactivesymptoms (ESb �1.0); noimprovement in nursery schoolobservations or psychological labtesting

Side effects: Most children experiencesignificant side effects (sadness,irritability, social withdrawal,insomnia, anorexia). Only threemothers chose to continue meds.

ohen et al,1981106

24 Kindergartenage

Parent andteacherConners’scale

3 months ofcognitive-behavioraltherapy, MPHa,both, none byrandomizedassignment

10–30 mg/day

Efficacy: no differences among groupsin behavior ratings or psychologicaltesting, but too few subjects tohave adequate power.

Side effects: not measured

arkley et al,1984104

18c 48–71;Mean � 61

Parent/teachercomplaintandConners’Parent Scale

21–30 days (7–10 days each onplacebo, lowdose, higherdose MPHa inrandomizedcrossoverdesign)

0.15 mg/kgbid or 0.50mg/kg bid

Efficacy: increase in compliance anddecrease in off-task behaviors instructured play; no difference inresponse between preschool andschool-aged children.

Side effects: higher dose producedmore side effects that lower doseor placebo; no difference in sideeffects between preschool andschool-aged

arkley,1988103

27 31–59;Mean � 47

Physiciandiagnosis,parentcomplaint,andConners’Parent Scale

21–30 days (7–10 days each onplacebo, lowdose, higherdose MPHa inrandomizedcrossoverdesign)


Efficacy: increase in compliance (ESb

�0.6) and decrease in off-taskbehaviors (ESb �0.5) duringstructured play at higher dose only

Side effects: no statistical differencesin treatment groups compared toplacebo in number or severity ofside effects

ayes et al,1994109

14c (10/14had

developmentaldisabilities)

22–60 DSM-III-Rcriteriabased onphysicianassessment

On average 26days (9 offmeds, 8 onmeds, 9 offmeds)

Starting dose0.3 mg/kgtid,increasedbased onresponse

Efficacy: improved parent rating scalesof ADHD symptoms (71%)

Side effects: 50% had some sideeffects (most common—irritability,anorexia, lethargy); no difference inrates between preschool andschool-aged children

ustin et al,1997110

31 48–70 DSM-III-Rcriteriabased onparent ratingscale

21–30 days (7–10on each dose,includingplacebo inrandomizedcrossover


Efficacy: improved parent rating scalesof ADHD symptoms (ESb low dose�0.5–0.7; ESb high dose �0.8–1.0); improved cognitive measuresof attention

Side effects: Mild side effects, only
design) seen at higher dose
0 Curr Probl Pediatr Adolesc Health Care, January 2006

itcttetaaWnt

aeasmddadc

sche

teepLswodcwd2dmqg

T

B

H

S

a

b

c

d ADHDe ine sa

C

mprovement were measured or could be determined,hey ranged from 0.50 to 1.00 in typically developinghildren. Most studies indicated that higher doses (0.5o 0.6 mg/kg/dose) were more likely to show efficacyhan lower doses (0.15 to 0.30 mg/kg/dose). In gen-ral, children received doses of methylphenidate of 5o 10 mg twice daily. None of the studies, however,ddressed determining appropriate starting doses for thisge group or evaluated titration to most effective dose.hen school-aged children were included in the studies,

o difference in response to medication was seen be-ween school-aged and preschool-aged children.Safety. Eight of the studies reported on side effects

s well as efficacy (Table 4). Most reported that sideffects were mild.103,104,107,110,112 In contrast, Shleifernd colleagues found that most children experiencedignificant side effects, which led to discontinuance ofedication.111 Two studies included school-aged chil-

ren as well as preschool children and reported noifferences in frequency of side effects based on thege of the child.104,109 Two of the studies focused onevelopmentally disabled children and found an in-

ABLE 4. Double-blind placebo-controlled trials of methylphenidate in pre

StudyNo. preschool

subjectsAge (months)

Diagnosticcriteria

yrne et al,1998105

16; 8 ADHD 8controls

48–72;Mean � 63

DSM-IV by 2psychologists;Conners’ParentRating Scale

5 m

anden et al,1999108

11 (all withdevelopmental

disabilities)

48–61;Mean � 59

Teacher ratingon behaviorquestionnaireandConners’ParentRating Scale

21

hort et al,2004112

28e 48–71;Mean � 63

DSM-IV criteriabased onparent ratingscale

21

Methylphenidate.Effect size: differences between groups expressed in units of standard deviatStudy included both preschool and school-aged children; number of subjectsTwo of eight children with ADHD on d-amphetamine; six of eight children withTwenty-two children on methylphenidate bid, six children on mixed amphetam

rease in side effects in this group of children, with O


ide effects seen in approximately 45 to 50% ofhildren given methylphenidate.108,109 In general,igher doses of medication produced more sideffects.104,110

Firestone and colleagues re-examined the data fromheir efficacy study and reported in detail on sideffects seen in preschool children.113 Significant sideffects were only reported in higher doses of methyl-henidate (0.5 mg/kg/dose) as compared to placebo.ower doses (0.3 mg/kg/dose) showed no increase inide effects. Sadness, anorexia, drowsiness, socialithdrawal, and nightmares were the side effects thatccurred more frequently at higher dose methylpheni-ate. For example, anorexia was seen in 81% ofhildren on higher dose methylphenidate, and socialithdrawal was seen in 75% of children on the higherose. These side effects were severe in 19% (sadness),2% (anorexia), 16% (drowsiness), 12% (social with-rawal), and 6% (nightmares) of these children. Whileost children experienced mild side effects, the fre-

uency and severity of these side effects appear to bereater than that reported in school-aged children.114

ol children with ADHD symptoms (continued)

tion andy design

MPHa dose Results: efficacy and side effects

s; case-l, before-

treatmentn

5–10 mg bidor tid asprescribedbycommunityphysiciand

Efficacy: improved parent rating scalesof AHDH symptoms, attention, andsocial skills; improvement inlaboratory measures of continuousperformance and attention

Side effects: not measured(7 days

ch dose,ingbo inmizedovern)

0.3 mg/kg or0.6 mg/kgq am, orbid or tid

Efficacy: improved teacher ratingscales of ADHD symptoms (ESb

�1.3–2.0) at higher dose; 73%judged to be “responders” (40%decrease in Conner’s score)

Side effects: 45% had side effects,especially dullness, socialwithdrawal, anorexia; side effectsmore severe at higher dose

ays (7on eachincluding

bo inmizedovern)

5 mg, 10mg, andplacebobid; someof olderchildrenalso given15 mg bid

Efficacy: improved parent rating scalesof DSM-IV ADHD symptoms on bestdose (5 or 10 mg for most); 68% ontreatment “normalized” (T score�60) versus 22% on placebo;similar improvement on teacherratings

Side effects: 15% experienced mildside effects, none causingtermination of treatment

e of subjects represents number and age of preschool children.on methylphenidate.

lts q am.

scho

Durastud

onthcontroafterdesig

dayson eaincludplacerandocrossdesig

–28 ddaysdose,placerandocrossdesig

ions.and ag

f additional concern, decreased caloric intake and

21

seaolc

ftasptt

asNsrcf

1

2

3

4

5

bAPPMp

st7sdAsscsdsw

pAdat5deueeeomsfPup

sslAtcppfdtoakk

2

ocial withdrawal could have more long-term negativeffects on young children going through rapid physicalnd mental growth. Unfortunately, while lower dosesf methylphenidate seemed to cause few side effects,ower doses were also much less likely to be effica-ious in improving ADHD symptomatology.Certain symptoms, often considered to be side ef-

ects of methylphenidate, actually decreased withreatment in some studies.112,113 Irritability, insomnia,nd anxiety significantly decreased in frequency andeverity in children taking higher doses of methyl-henidate. Thus, these symptoms are most likely dueo ADHD itself and are therefore ameliorated byreatment with methylphenidate.Preschool ADHD Treatment Study (PATS). To

ddress the gaps in our knowledge in the efficacy andafety of stimulant medication in young children, theational Institute of Mental Health funded the Pre-

chool ADHD Treatment Study (PATS), a multisite,andomized controlled trial of methylphenidate inhildren 3 to 5.5 years of age.115 The PATS has theollowing phases:

. Parent Training: Families participate in 10-weekparent training. Those children not demonstrating adecrease in ADHD symptoms of 30% or greater areasked to enter the methylphenidate trials.

. Titration Trial: As in the MTA study, subjects areentered into a 5-week double-blind, randomizedwithin-subject crossover design trial to determineoptimal dose of methylphenidate. Starting dose inthe PATS is 1.25 mg tid and the maximum dose is10 mg tid.

. Parallel Trial: Subjects are then entered into a4-week double-blind, randomized, placebo-con-trolled study at their optimal dose. Clinical re-sponse was defined as at least a 25% decrease ofADHD symptoms based on parent–teacher ratings.

. Open-Label Trial: 42 weeks of open-label treat-ment to assess safety.

. Discontinuation Trial: At the end of the open-labeltrial, subjects are randomized to either methyl-phenidate or placebo for a 6-week period.

Results of the PATS have not yet been published,ut have been presented at several scientific meetings.t the American Academy of Child and Adolescentsychiatry Annual Meeting in October 2004, theATS investigators shared preliminary results.116

ost children did not sufficiently respond to the
arent-training program. Eighty-five percent of pre- u
2

chool children responded to methylphenidate in theitration trial. This response rate is comparable to the7% response rate of school-age children in the MTAtudy.117 Most children were titrated to an optimalose of methylphenidate between 1.25 and 7.5 mg tid.small number of children required 10 mg tid. Effect

izes of response in preschool children, however, wereomewhat smaller than those found for school-agehildren in the MTA study.117 In the parallel trial,lightly less than half of the children on methylpheni-ate had clinically significant decreases in ADHDymptomatology. Side-effect data and longer term (42eek) efficacy data have not yet been reported.Summary of Efficacy and Safety Data. Methyl-henidate appears to be efficacious in the treatment ofDHD symptoms and impairment in preschool chil-ren. Effect sizes of the decrease in ADHD symptom-tology are somewhat smaller in preschool childrenhan in school-aged children. Doses of approximately

mg tid are generally effective. A broad range ofoses may be optimal for the individual child, how-ver, ranging from 1.25 to 10 mg/dose. Side effects aresually mild, but the frequency and severity of sideffects are greater than in school-aged children. Sideffects such as social withdrawal and anorexia areven more a matter for concern in the rapidly devel-ping preschooler than in the school-aged child. Al-ost no children under the age of 3 years have been

tudied, and therefore, medication has unknown ef-ects and safety in those children. Results from theATS, as they become available, will further ournderstanding of the efficacy and safety of methyl-henidate in young children.Other Concerns Regarding the Use of Psycho-

timulants in Preschool Children. Several other is-ues face the practitioner who considers using stimu-ants in the treatment of preschool children withDHD. Oddly, while all the randomized controlled

rials studying the efficacy of stimulants in preschoolhildren, including the PATS, have studied methyl-henidate, the Food and Drug Administration ap-roves product labeling for amphetamine preparationsor ADHD down to age 3 years and for methylpheni-ate down to age 6 years.27 Thus the clinician is forcedo use methylphenidate in preschool children as anff-label drug, while at the same time is able to usemphetamines in preschool children with much lessnowledge of efficacy and safety. There is also nonown starting dose for preschool children. The PATS
sed 1.25 mg tid as the starting dose, and some of the

cdsliFsttapld

Ei

naotiibtgrAtcssstoamcacigtmablgsm

tstTemesas

TstcrcatsaetooRbc

astysflidPmop

wcinat

C

hildren were found to have this dose as their “bestose.”32,116 Therefore, at this time, 1.25 mg wouldeem a reasonable starting dose. However, since theowest strength tablets available are 5 mg, the clinicians forced to ask parents to cut tablets in quarters.urthermore, swallowing pills is problematic for pre-choolers. Either these young children have to beaught to swallow pills using behavioral training, orheir parents need to find a pharmacy that will prepareliquid suspension, or their parents have to crush the

ill in applesauce themselves. All of these issues mayead to inaccurate dosing or nonstandard absorptionynamics.

fficacy of Behavioral Treatments for ADHDn Preschool Children

Behavioral Treatments for School-Age Children. Aumber of psychosocial treatments have been shown,t least in the short term, to be useful in the treatmentf ADHD in school-aged children. Clinical behaviorherapy involving either parent training, teacher train-ng, direct contingency management by trained behav-oral staff in a school setting, or intensive packagedehavioral treatments (combinations of parent andeacher training, often combined with direct contin-ency management) are empirically supported by theesearch literature for school-aged children withDHD.82 In contrast, cognitive-behavioral interven-

ions have not been shown to produce importanthanges in the behavior or academic achievement ofchool-aged children with ADHD.82 While the inten-ive packaged behavioral treatment of the MTAtudy118,119 was not found to be better than the routinereatment community comparison,83 as was pointedut previously in this article, there are several cautionsbout the over-interpretation of this data. First, theajority of the children (two-thirds) in the routine

ommunity comparison were receiving stimulant ther-py.84 Therefore, the behavioral treatment was beingompared to a suboptimal stimulant treatment compar-son group rather than a placebo or wait-list controlroup. Furthermore, secondary analyses indicated thathe behavioral treatment was superior to routine com-unity treatment in certain subgroups (children with

nxiety and low socioeconomic groups),84 and com-ining behavior therapy with medication allowed for aower medication dose.83,85 The clinical practiceuideline of the American Academy of Pediatricstates that clinicians should recommend stimulant
edication and/or behavior therapy as appropriate P

reatment for children with ADHD.120 However, thetrength of the evidence is only fair for behaviorherapy, whereas it is strong for stimulant medication.he practice parameters issued by the American Acad-my of Child and Adolescent Psychiatry recommendsedication, along with support and education of par-

nts and appropriate school placement, as “the corner-tones of treatment” and lists behavior modificationmong “other treatments” to address “remainingymptoms.”121

Reasons for Serious Consideration of Behaviorherapy in Preschool ADHD Children. There areeveral reasons to consider behavior therapy as areatment option even more seriously in preschoolhildren than in school-aged children. There is aeluctance on the part of most parents to start younghildren on psychostimulant medication.122 There islso concern among developmental-behavioral pedia-ricians and child psychiatrists about the long-termide effects of psychostimulants on the young brainnd body.27,32,89-91,123 Therefore, the American Acad-my of Child and Adolescent Psychiatry recommendshat clinicians consider starting stimulant medicationnly in the most severely symptomatic children andnly after a failed trial of behavioral therapy.121

eflecting these recommendations, the PATS had auilt-in trial of behavior therapy preceding its medi-ation trials.115,123,124

In addition to these concerns about the safety andcceptability of psychostimulant medication in pre-chool children, there are theoretical reasons to believehat behavior therapy may be more effective inounger children. In school-age children, ADHDymptoms have often become complicated by schoolailure and rejection by peers. These problems mayead to low self-esteem and a sense of demoralizationn the child with ADHD, which makes the child moreifficult to treat with behavioral modalities.125,126

sychosocial interventions in the preschool perioday be more effective because the intervention is

ccurring prior to the establishment of these additionalsychological problems.Parent-Training Programs for Preschool Childrenith ADHD. Preschool children with ADHD may beonsidered to have two different categories of behav-or that may be amenable to behavior therapy: (1)oncompliant behavior due either to their ADHDnd/or to associated ODD, and (2) ADHD core symp-oms of hyperactivity, distractibility, and impulsivity.
arent-training programs have generally focused on
23

tsgowurnrguedacsss

pmhtcttrdsipacapnwpptAaospcmpnt

gpmatskeacagc

SbpithilTtpcmsttmmppmbt

Tpdapcttiaw

2

he noncompliant behavior rather than core ADHDymptoms. The elements of most parent-training pro-rams have included instructing parents in the (1) usef positive reinforcement of pro-social behavior; (2)ithdrawal of attention for misbehavior through these of ignoring or time-out rather than negativeeinforcement of misbehavior through aversive tech-iques; (3) the appropriate issuing of commands andeprimands.122,127 Parent training is done in eitherroup or individual sessions. Parent-training programssing these types of techniques have been shown to beffective in reducing noncompliant behavior in chil-ren with ODD, ADHD, and ODD � ADHD, as wells improving parenting skills in the parents of thesehildren.128-131 However, in those studies that mea-ured core ADHD symptoms as an outcome, noignificant effect was seen on the core ADHDymptoms.129,131

Sonuga-Barke and colleagues have studied the ex-ansion of parent training beyond standard behavioralanagement techniques. In addition to standard be-

avioral management, the parent-training programhey designed promoted (1) effective limit setting; (2)larity in communications and establishment of rou-ines as a basis for authoritative parenting; and (3) aailored promotion of improved attention and self-egulation of the child. The treatment was givenuring eight 1-hour weekly visits with one of twopecially trained health visitor therapists in each fam-ly’s home. A randomized controlled trial of thisrogram was performed with comparison subjectsssigned to supportive parent counseling or wait-listontrols.122,132 Children were identified at 3 years ofge. Results of this study were encouraging, witharent training producing substantial statistically sig-ificant improvement in core ADHD symptoms asell as ODD symptoms when compared to eitherarent counseling or wait-list conditions. The effectsersisted 15 weeks after the end of the 8-weekreatment program. Effect sizes for improvement ofDHD symptoms were 0.69 and 0.87 for observed

nd parent-reported symptoms, respectively. Howevernly 53% of patients met criteria for a clinical re-ponse to parent training, implying that almost half ofreschool children with ADHD will still need to beonsidered for other therapies (including stimulantedication). Furthermore, when the investigators re-

eated their intervention with a group of nonspecialisturses in a primary care setting, there was no reduc-
ion of ADHD symptoms.133 This would imply that m
4

eneralizing the results of the original study to multi-le and diverse sites will be difficult. The difficulty ofaintaining the integrity of intervention techniques,

nd therefore the efficacy of the intervention, whenransferring a highly specialized intervention to a lesstructured environment was also encountered by Bar-ley and colleagues. They attempted to institute anvidence-based behavior therapy parenting program in

school system at kindergarten entry. Parents ofhildren identified with ADHD and ODD symptom-tology were offered 10-week parent-training pro-ram, but very poor attendance led to no significanthange in ADHD symptoms or disruptive behavior.134

A secondary analysis of the results of both of theonuga–Barke studies described above was performedy the investigators. This analysis revealed that theresence or absence of maternal ADHD was anmportant factor in the child’s response to the parent-raining program. Those children whose mothers hadigh ADHD symptomatology had no response to thentervention, while those children whose mothers hadow ADHD symptomatology responded quite well.he association of maternal ADHD symptoms with

heir child’s response to the parent-training programersisted after controlling for the intensity of thehild’s ADHD symptoms, the family’s SES, maternalental health, and other factors in regression analy-

es.135 The authors discuss possible mechanisms forhe importance of maternal ADHD, including cogni-ive and organizational impairment of the mother,aternal difficulties in interpersonal relationships, andaternal motivational style. They also suggest the

ossibility that ADHD diagnosed in children witharents exhibiting a high level of ADHD symptomsay be more biogenetically based and may therefore

e more likely to require psychopharmacologicherapy.Behavioral Interventions in the Preschool Setting.here is little known about ADHD interventions in thereschool setting, through either teacher training orirect contingency management of the child. Barkleynd colleagues studied 5-year-olds in kindergarten androvided an intensive behavioral program that in-luded teacher and teacher aide training; an intensiveoken system; response cost, over-correction, andime-out from reinforcement; group social skills train-ng, cognitive-behavioral self-control training, andnger training; a daily school report card of behaviorith home-based reinforcement; targeted behavior
odification at recess and bus rides; and academic

saainttmticapMtahors

secdteBvmtesm

pombpgpttciwwot

tficstftb

SD

●

●

●

●

●

C

kills training. Results indicated a reduction of hyper-ctive, impulsive, inattentive, and aggressive behaviors well as improvement of social skills and self-controln disruptive children.134 However, evaluators wereot blinded to the treatment status of the children andhat may have biased their assessments to more posi-ive outcomes. In addition, the behavioral improve-ents in the school kindergarten did not generalize to

he home environment, and there was no evidence ofmprovement of academic achievement. Finally, thesehildren were “older” preschool children, and gener-lization of these findings to 3- and 4-year-olds inreschool settings is not possible. One other study, bycGoey and colleagues, examined the effects of a

eacher training program using positive reinforcementnd cost-response intervention on the disruptive be-avior of preschool children with ADHD. Directbservations of behavior indicated decreases in dis-uptive behavior, but no measurement of core ADHDymptoms was included.136

Summary of Behavioral Interventions for Pre-chool Children with ADHD. There is reasonablevidence that parent-training programs improve non-ompliant and disruptive behavior in preschool chil-ren with ADHD. There is only one study, however,hat has looked for, and found, a clinically significantffect of parent training on core ADHD symptoms.ehavioral interventions in the preschool setting, in-olving teacher training or direct contingency manage-ent of children, are more poorly studied than parent-

raining interventions. No firm conclusions about theirffectiveness can be reached. Multimodal treatmenttudies of preschool ADHD, looking at combinededication and behavioral therapies, do not exist.The effectiveness of parent-training programs ap-ears to be dependent on maintenance of the integrityf the intervention with highly specialized and com-itted professional staff. Availability of large num-

ers of such professionals in most communities isroblematic. Yet, without such professionals, pro-rams do not appear to be effective. Parent-trainingrograms also seem to be ineffective when parentshemselves, as commonly occurs, have ADHD. Fur-hermore, approximately 50% of children will show alinical improvement when their parents are enrolledn such programs, leaving the other half of childrenith ADHD in need of alternative treatments. Finally,hile many parents reject pharmacological treatmentf their preschool children with ADHD, parents find
he large commitment they need to make to behavioral

reatments difficult to sustain. As a result, parents arerequently nonadherent to required attendance at train-ng sessions, especially if the sessions are offered atlinical facilities and not in local community or homeettings.137 Thus the clinician is frequently left withhe conundrum of wanting to avoid stimulant therapyor preschool children with ADHD, but being unableo provide alternative evidenced-based, acceptableehavioral therapy programs to families.

ummary and Conclusionsiagnosis and Prevalence

Despite concerns about the applicability and word-ing of DSM-IV criteria for the diagnosis of ADHDin preschool children, DSM-IV-based ADHD par-ent and teacher rating scales, developed for use withschool-age children, have been shown to be reliablewhen used with preschool children.The overall prevalence rate of ADHD in preschoolchildren is 4.9% This prevalence rate is similar tothe prevalence rate of ADHD for school-aged chil-dren (5.8%).The prevalence rates of ADHD subtypes in pre-school children are markedly different from that inschool-aged children. Most school-aged childrenhave either the inattentive (48%) or the combined(43%) subtypes and very few have the hyperactive-impulsive (9%) subtype. In comparison, for pre-school children prevalence rates of the inattentiveand hyperactive-impulsive subtypes are reversed.Forty-eight percent of preschool children are diag-nosed with the hyperactive-impulsive subtype andonly 13% are diagnosed as having the inattentivesubtype.Gender differences are less pronounced in pre-school children than in older children. The ratio ofboys to girls diagnosed with ADHD in the pre-school age group is 2:1, compared to 3:1 in school-aged children.Preschool children are likely to have comorbidities,especially ODD. At least half of preschool childrenwith ADHD have a comorbidity (ODD, CD, depres-sion, anxiety) and in approximately one-third of thecases there are two or more comorbidities. Theaddition of the diagnosis of ODD is likely to be amarker for more severe ADHD symptomatology.Even those children without the diagnosis of ODD
are likely to have some oppositional behaviors.
25

●

T

●

●

●

●

●

●

●

●

●

2

Despite concerns about the overdiagnosis of ADHDin preschool children, the DSM-IV criteria appearto be valid for diagnosis of ADHD in this agegroup. There is ample evidence that young childrenidentified by DSM-IV criteria as having ADHDhave significant impairments in psychosocial andacademic functioning, including impaired relation-ships with parents, siblings, teachers, and peers;school suspension; deficient social skills and pre-academic skills; and increased incidence of acciden-tal injury. There is also stability of ADHD symp-toms and diagnosis, as well as psychosocial andacademic impairment, from the preschool periodinto school age. The construct validity of DSM-IVcriteria in preschool children is supported by findinga “dose effect” of number of symptoms on impair-ment, and a neuropsychological profile similar tothat in school-aged children.

reatment

The treatment modalities that are available forpreschool children are the same as for school-agedchildren: psychostimulant medication and behaviortherapy.Families, clinicians, researchers, and the publichave strongly felt concerns about the use of psy-chostimulants in young children. These concernsare based on potential dangers to a changing andplastic nervous system, including altering thecourse of neurodevelopment. There is scientificevidence from animal experiments to support theseconcerns.There is controversy over whether psychostimulantmedication causes permanent deficits in lineargrowth in school-aged children and adolescentswith ADHD. However, school-aged children withADHD on psychostimulants appear to have modestdeficits in linear growth, at least in the short term.There are no studies looking at linear growth inyoung children on psychostimulant medications.However, the more rapid growth rate of the youngchild raises concerns about growth suppression atsuch a young age.Based on a small number of double-blind placebocontrolled studies, and preliminary informationfrom a new multicenter randomized controlled trial(PATS), methylphenidate appears to be efficaciousin the treatment of ADHD symptoms and impair-ment in preschool children. Effect sizes of the
decrease in ADHD symptoms are somewhat smaller
6

in preschool children than in school-aged children.Methylphenidate doses of 5 mg tid are generallyeffective, although a broad range of doses (rangingfrom 1.25 to 10 mg/dose) may be optimal for theindividual child. It seems prudent to start with adose of 1.25 mg, especially in the 3- to 4-year-old.Side effects are usually mild, but the frequency andseverity of side effects are greater than in school-aged children. Side effects such as social with-drawal and anorexia are even more a matter forconcern in the rapidly developing preschool childthan in the school-aged child.Because of concerns about safety, the AmericanAcademy of Child and Adolescent Psychiatry rec-ommends that clinicians consider starting psycho-stimulant medication only in the most severelysymptomatic preschool children and only after afailed trial of behavioral therapy.There is no information on the efficacy and sideeffects of psychostimulants under the age of 3. Theclinician should be wary of prescribing psycho-stimulants to children under the age of 3 for thediagnosis of ADHD.Results of the PATS, as they become available, willfurther our understanding of the efficacy and safetyof methylphenidate in young children.There is evidence that behavioral-based parent-training programs improve noncompliant and dis-ruptive behavior in preschool children with ADHD.However, there is only preliminary research on thedesign and effect of parent-training programs oncore ADHD symptoms. While this research showspromising results, efficacy depends on the availabil-ity of appropriately trained and supervised profes-sionals in the local community. Parent training alsoseems to be ineffective when the parent has ADHD.Many parents find the large commitment of timeand effort required by parent-training programsdifficult to sustain. Therefore, while behavioraltherapy programs are recommended as the first lineof treatment for preschool ADHD, effective andaccessible programs may not be available to fami-lies in many communities.

References1. Faraone SV. The scientific foundation for understanding

attention-deficit/hyperactivity disorder as a valid psychiatricdisorder. Eur Child Adolesc Psychiatry 2005;14(1):1-10.

2. Faraone SV, Biederman J. Neurobiology of attention-deficit
hyperactivity disorder. Biol Psychiatry 1998;44(10):951-8.

C

3. Sprich S, Biederman J, Crawford MH, et al. Adoptive andbiological families of children and adolescents with ADHD.J Am Acad Child Adolesc Psychiatry 2000;39(11):1432-7.

4. Achenbach TM, Rescorla L. Manual for the ASEBA pre-school forms and profiles: an integrated system of multi-informant assessment. Burlington, VT: University of Ver-mont, Research Center for Children, Youth, and Families;2000.

5. Rietveld MJ, Hudziak JJ, Bartels M, et al. Heritability ofattention problems in children: I. Cross-sectional results froma study of twins, age 3-12 years. Am J Med Genet BNeuropsychiatr Genet 2003;117(1):102-13.

6. Price TS, Simonoff E, Waldman I, et al. Hyperactivity inpreschool children is highly heritable. J Am Acad ChildAdolesc Psychiatry 2001;40(12):1362-4.

7. Cook EH. Genetics of attention-deficit hyperactivity disor-der. Ment Retard Dev Disabil Res Rev 1999;5(3):191-8.

8. Kahn RS, Khoury J, Nichols WC, et al. Role of dopaminetransporter genotype and maternal prenatal smoking in child-hood hyperactive-impulsive, inattentive, and oppositionalbehaviors. J Pediatr 2003;143(1):104-10.

9. Schmidt LA, Fox NA, Perez-Edgar K, et al. Association ofDRD4 with attention problems in normal childhood devel-opment. Psychiatr Genet 2001;11(1):25-9.

10. Jensen PS. ADHD: current concepts on etiology, pathophys-iology, and neurobiology. Child Adolesc Psychiatr Clin NAm 2000;9(3):557-72, vii-viii.

11. Mercugliano M. What is attention-deficit/hyperactivity dis-order? Pediatr Clin North Am 1999;46(5):831-43.

12. Schothorst PF, van Engeland H. Long-term behavioral se-quelae of prematurity. J Am Acad Child Adolesc Psychiatry1996;35(2):175-83.

13. Lou HC. Etiology and pathogenesis of attention-deficit hy-peractivity disorder (ADHD): significance of prematurity andperinatal hypoxic-haemodynamic encephalopathy. Acta Pae-diatr 1996;85(11):1266-71.

14. Lou HC, Rosa P, Pryds O, et al. ADHD: increased dopaminereceptor availability linked to attention deficit and lowneonatal cerebral blood flow. Dev Med Child Neurol2004;46(3):179-83.

15. Thapar A, Fowler T, Rice F, et al. Maternal smoking duringpregnancy and attention deficit hyperactivity disorder symp-toms in offspring. Am J Psychiatry 2003;160(11):1985-9.

16. Faraone SV, Doyle AE. The nature and heritability ofattention-deficit/hyperactivity disorder. Child Adolesc Psy-chiatr Clin N Am 2001;10(2):299-316, viii-ix.

17. Needleman HL, Riess JA, Tobin MJ, et al. Bone lead levelsand delinquent behavior. JAMA 1996;275(5):363-9.

18. Mendelsohn AL, Dreyer BP, Fierman AH, et al. Low-levellead exposure and behavior in early childhood. Pediatrics101(3):E10, 1998.

19. Konofal E, Lecendreux M, Arnulf I, et al. Iron deficiency inchildren with attention-deficit/hyperactivity disorder. ArchPediatr Adolesc Med 2004;158(12):1113-5.

20. Beard J. Iron deficiency alters brain development and func-tioning. J Nutr 2003;133(5 Suppl 1):1468S-72S.

21. O’Brien LM, Holbrook CR, Mervis CB, et al. Sleep and
neurobehavioral characteristics of 5- to 7-year-old children

with parentally reported symptoms of attention-deficit/hyperactivity disorder. Pediatrics 2003;111(3):554-63.

22. Ali NJ, Pitson DJ, Stradling JR. Snoring, sleep disturbance,and behaviour in 4-5 year olds. Arch Dis Child1993;68(3):360-6.

23. Cunningham CE, Boyle MH. Preschoolers at risk for atten-tion-deficit hyperactivity disorder and oppositional defiantdisorder: family, parenting, and behavioral correlates. JAbnorm Child Psychol 2002;30(6):555-69.

24. Christakis DA, Zimmerman FJ, DiGiuseppe DL, et al. Earlytelevision exposure and subsequent attentional problems inchildren. Pediatrics 2004;113(4):708-13.

25. American Psychiatric Association. Diagnostic and statisticalmanual of mental disorders: DSM-IV-TR. 4th, text revision.ed. Washington, DC: American Psychiatric Association;2000.

26. Palfrey JS, Levine MD, Walker DK, et al. The emergence ofattention deficits in early childhood: a prospective study. JDev Behav Pediatr 1985;6(6):339-48.

27. Connor DF. Preschool attention deficit hyperactivitydisorder: a review of prevalence, diagnosis, neurobiology,and stimulant treatment. J Dev Behav Pediatr 23(1 Suppl):S1-9, 2002.

28. Blackman JA. Attention-deficit/hyperactivity disorder in pre-schoolers. Does it exist and should we treat it? Pediatr ClinNorth Am 1999;46(5):1011-25.

29. Lahey BB, Applegate B, McBurnett K, et al. DSM-IV fieldtrials for attention deficit hyperactivity disorder in childrenand adolescents. Am J Psychiatry 1994;151(11):1673-85.

30. Lahey BB, Pelham WE, Stein MA, et al. Validity of DSM-IVattention-deficit/hyperactivity disorder for younger children.J Am Acad Child Adolesc Psychiatry 1998;37(7):695-702.

31. Perrin EC. Maternal report of attention deficit hyperactivitydisorder symptoms in preschool children (commentary).Child Care Health Dev 2000;26:176-178.

32. Greenhill LL, Pliszka S, Dulcan MK, et al. Practice param-eter for the use of stimulant medications in the treatment ofchildren, adolescents, and adults. J Am Acad Child AdolescPsychiatry 2002;41(2 Suppl):26S-49S.

33. American Academy of Pediatrics. Clinical practice guideline:diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. Pediatrics 2000;105(5):1158-70.

34. Brown RT, Freeman WS, Perrin JM, et al. Prevalence andassessment of attention-deficit/hyperactivity disorder in pri-mary care settings. Pediatrics 107(3):E43, 2001.

35. Conners CK, Sitarenios G, Parker JD, et al. The revisedConners’ Parent Rating Scale (CPRS-R): factor structure,reliability, and criterion validity. J Abnorm Child Psychol1998;26(4):257-68.

36. Conners CK. Conners’ Rating Scales-Revised technical man-ual. Toronto, Ontario: Multi-health Systems, Inc.; 2000.

37. DuPaul GJ, Power TJ, Anastopoulos AD, et al. Manual forthe AD/HD Rating Scale-IV. New York: Guilford Press;1998.

38. Gadow KD, Sprafkin JN. Early Childhood Symptom Inven-tory-4 norms manual. Stony Brook, NY: Checkmate Plus,Ltd.; 1997.

39. Sprafkin J, Volpe RJ, Gadow KD, et al. A DSM-IV-
referenced screening instrument for preschool children: the
27

2

Early Childhood Inventory-4. J Am Acad Child AdolescPsychiatry 2002;41(5):604-12.

40. Gadow KD, Sprafkin JN. ADHD symptom checklist-4 man-ual. Stony Brook, NY: Checkmate Plus, Ltd.; 1997.

41. Wolraich ML, Feurer ID, Hannah JN, et al. Obtaining system-atic teacher reports of disruptive behavior disorders utilizingDSM-IV. J Abnorm Child Psychol 1998;26(2):141-52.

42. Wolraich ML, Hannah JN, Baumgaertel A, et al. Examina-tion of DSM-IV criteria for attention deficit/hyperactivitydisorder in a county-wide sample. J Dev Behav Pediatr1998;19(3):162-8.

43. Wolraich ML, Lambert W, Doffing MA, et al. Psychometricproperties of the Vanderbilt ADHD diagnostic parent ratingscale in a referred population. J Pediatr Psychol2003;28(8):559-67.

44. Johnson D. Getting your arms around ADHD: new tools tohelp pediatricians implement Academy’s recent diagnosticguidelines. AAP News 64;21(2):64.

45. Swanson JM. School-based assessments and interventionsfor ADD students. Irvine, CA: KC Publications; 1992.

46. Swanson JM, Kraemer HC, Hinshaw SP, et al. Clinicalrelevance of the primary findings of the MTA: success ratesbased on severity of ADHD and ODD symptoms at the endof treatment. J Am Acad Child Adolesc Psychiatry2001;40(2):168-79.

47. Egger HL, Angold A. The Preschool Age Psychiatric As-sessment (PAPA): a structured parent interview for diagnos-ing psychiatric disorders in preschool children. In: DelCar-men-Wiggins R, Carter A, editors. Handbook of Infant,Toddler, and Preschool Mental Health Assessment. NewYork: Oxford University Press; 2004. p. 223-43.

48. Egger HL, Kondo D, Angold A. The epidemiology ofpreschool ADHD: a review. Infants Young Child 2005 (inpress).

49. Ford T, Goodman R, Meltzer H. The British Child andAdolescent Mental Health Survey 1999: the prevalence ofDSM-IV disorders. J Am Acad Child Adolesc Psychiatry2003;42(10):1203-11.

50. Wolraich ML, Hannah JN, Pinnock TY, et al. Comparison ofdiagnostic criteria for attention-deficit hyperactivity disorderin a county-wide sample. J Am Acad Child Adolesc Psychi-atry 1996;35(3):319-24.

51. Lavigne JV, Gibbons RD, Christoffel KK, et al. Preva-lence rates and correlates of psychiatric disorders amongpreschool children. J Am Acad Child Adolesc Psychiatry1996;35(2):204-14.

52. Keenan K, Shaw DS, Walsh B, et al. DSM-III-R disorders inpreschool children from low-income families. J Am AcadChild Adolesc Psychiatry 1997;36(5):620-7.

53. Gimpel GA, Kuhn BR. Maternal report of attention deficithyperactivity disorder symptoms in preschool children. ChildCare Health Dev 2000;26(3):163-76; discussion 176-9.

54. Gadow KD, Sprafkin J, Nolan EE. DSM-IV symptoms incommunity and clinic preschool children. J Am Acad ChildAdolesc Psychiatry 2001;40(12):1383-92.

55. Orvaschel H, Puig-Antich J. Schedule for affective disordersand schizophrenia for school-age children—epidemiologic4th version. Ft. Lauderdale, FL: Bova University Center for
Psychological Study; 1987.
8

56. Nolan EE, Gadow KD, Sprafkin J. Teacher reports of DSM-IVADHD, ODD, and CD symptoms in schoolchildren. J Am AcadChild Adolesc Psychiatry 2001;40(2):241-9.

57. Egger HL. Epidemiology and nosology of ADHD in pre-school children. Presented at the annual meeting of thePediatric Academic Societies, Washington, DC, May, 2005.

58. Kadesjo C, Hagglof B, Kadesjo B, et al. Attention-deficit-hyperactivity disorder with and without oppositional defiantdisorder in 3- to 7-year-old children. Dev Med Child Neurol2003;45(10):693-9.

59. DuPaul GJ, McGoey KE, Eckert TL, et al. Preschool childrenwith attention-deficit/hyperactivity disorder: impairments inbehavioral, social, and school functioning. J Am Acad ChildAdolesc Psychiatry 2001;40(5):508-15.

60. Lonigan CJ, Bloomfield BG, Anthony JL, et al. Relationsamong emergent literacy skills, behavior problems, andsocial competence in preschool children from low- andmiddle-income backgrounds. Top Early Child Spec Educ1999;19(1):40-54.

61. Mendelsohn AL. Promoting language and literacy throughreading aloud: the role of the pediatrician. Curr Probl PediatrAdolesc Health Care 2002;32(6):188-202.

62. Camarata SM, Gibson T. Pragmatic language deficits inattention-deficit hyperactivity disorder (ADHD). Ment Re-tard Dev Disabil Res Rev 1999;5(3):207-14.

63. Rabiner D, Coie JD. Early attention problems and children’sreading achievement: a longitudinal investigation. The Con-duct Problems Prevention Research Group. J Am Acad ChildAdolesc Psychiatry 2000;39(7):859-67.

64. Armstrong MB, Nettleton SK. Attention deficit hyperactivitydisorder and preschool children. Semin Speech Lang2004;25(3):225-32.

65. Arnold DH. Co-occurrence of externalizing behavior prob-lems and emergent academic difficulties in young high-riskboys: a preliminary evaluation of patterns and mechanisms.J Appl Dev Psychol 1997;18(3):317-30.

66. Spira EG, Fischel JE. The impact of preschool inattention,hyperactivity, and impulsivity on social and academicdevelopment: a review. J Child Psychol Psychiatry2005;46(7):755-73.

67. Wolraich ML. Attention deficit hyperactivity disorder: themost studied and yet most controversial diagnosis. MentRetard Dev Disabil Res Rev 1999;5(3):163-8.

68. Campbell SB, Ewing LJ, Breaux AM, et al. Parent-referredproblem three-year-olds: follow-up at school entry. J ChildPsychol Psychiatry 1986;27(4):473-88.

69. Campbell SB, Ewing LJ. Follow-up of hard-to-managepreschoolers: adjustment at age 9 and predictors of continuingsymptoms. J Child Psychol Psychiatry 1990;31(6):871-89.

70. McGee R, Partridge F, Williams S, et al. A twelve-yearfollow-up of preschool hyperactive children. J Am AcadChild Adolesc Psychiatry 1991;30(2):224-32.

71. Egeland B, Kalkoske M, Gottesman N, et al. Preschoolbehavior problems: stability and factors accounting forchange. J Child Psychol Psychiatry 1990;31(6):891-909.

72. Lahey BB, Pelham WE, Loney J, et al. Three-year predictivevalidity of DSM-IV attention deficit hyperactivity disorder inchildren diagnosed at 4-6 years of age. Am J Psychiatry
2004;161(11):2014-20.

1

1

1

1

1

1

1

1

C

73. Durston S. A review of the biological bases of ADHD: whathave we learned from imaging studies? Ment Retard DevDisabil Res Rev 2003;9(3):184-95.

74. Nigg JT, Blaskey LG, Huang-Pollock CL, et al. Neuropsycho-logical executive functions and DSM-IV ADHD subtypes.J Am Acad Child Adolesc Psychiatry 2002;41(1):59-66.

75. Sergeant JA, Geurts H, Oosterlaan J. How specific is a deficitof executive functioning for attention-deficit/hyperactivitydisorder?. Behav Brain Res 2002;130(1-2):3-28.

76. Sergeant JA, Geurts H, Huijbregts S, et al. The top and thebottom of ADHD: a neuropsychological perspective. Neuro-sci Biobehav Rev 2003;27(7):583-92.

77. Sonuga-Barke EJ. Psychological heterogeneity in AD/HD—a dual pathway model of behaviour and cognition.Behav Brain Res 2002;130(1-2):29-36.

78. Geurts HM, Verte S, Oosterlaan J, et al. How specific areexecutive functioning deficits in attention deficit hyperactiv-ity disorder and autism?. J Child Psychol Psychiatry2004;45(4):836-54.

79. Sonuga-Barke EJ, Dalen L, Remington B. Do executive deficitsand delay aversion make independent contributions to preschoolattention-deficit/hyperactivity disorder symptoms? J Am AcadChild Adolesc Psychiatry 2003;42(11):1335-42.

80. Hughes C, Dunn J, White A. Trick or treat?: unevenunderstanding of mind and emotion and executive dysfunc-tion in “hard-to-manage” preschoolers. J Child PsycholPsychiatry 1998;39(7):981-94.

81. Spencer T, Biederman J, Wilens T, et al. Pharmacotherapy ofattention-deficit hyperactivity disorder across the life cycle.J Am Acad Child Adolesc Psychiatry 1996;35(4):409-32.

82. Pelham Jr, WE Wheeler T, Chronis A. Empirically supportedpsychosocial treatments for attention deficit hyperactivitydisorder. J Clin Child Psychol 1998;27(2):190-205.

83. MTA Cooperative Group. A 14-month randomized clinicaltrial of treatment strategies for attention-deficit/hyperactivitydisorder. Multimodal Treatment Study of Children withADHD. Arch Gen Psychiatry 1999;56(12):1073-86.

84. MTA Cooperative Group. Moderators and mediators oftreatment response for children with attention-deficit/hyper-activity disorder: the Multimodal Treatment Study of chil-dren with Attention-deficit/hyperactivity disorder. Arch GenPsychiatry 1999;56(12):1088-96.

85. MTA Cooperative Group. National Institute of Mental HealthMultimodal Treatment Study of ADHD follow-up: 24-monthoutcomes of treatment strategies for attention-deficit/hyperac-tivity disorder. Pediatrics 2004;113(4):754-61.

86. MTA Cooperative Group. National Institute of MentalHealth Multimodal Treatment Study of ADHD follow-up:changes in effectiveness and growth after the end of treat-ment. Pediatrics 2004;113(4):762-9.

87. Zito JM, Safer DJ, dosReis S, et al. Trends in the prescribingof psychotropic medications to preschoolers. JAMA2000;283(8):1025-30.

88. Rappley MD, Eneli IU, Mullan PB, et al. Patterns ofpsychotropic medication use in very young children withattention-deficit hyperactivity disorder. J Dev Behav Pediatr2002;23(1):23-30.

89. Coyle JT. Psychotropic drug use in very young children.
JAMA 2000;283(8):1059-60.

90. Diller LH. Lessons from three year olds. J Dev Behav Pediatr23(1 Suppl):S10-2, 2002.

91. Minde K. The use of psychotropic medication inpreschoolers: some recent developments. Can J Psychiatry1998;43(6):571-5.

92. Moll GH, Hause S, Ruther E, et al. Early methylphenidateadministration to young rats causes a persistent reduction inthe density of striatal dopamine transporters. J Child AdolescPsychopharmacol 2001;11(1):15-24.

93. Bolanos CA, Barrot M, Berton O, et al. Methylphenidatetreatment during pre- and periadolescence alters behavioralresponses to emotional stimuli at adulthood. Biol Psychiatry2003;54(12):1317-29.

94. Brandon CL, Marinelli M, White FJ. Adolescent exposure tomethylphenidate alters the activity of rat midbrain dopamineneurons. Biol Psychiatry 2003;54(12):1338-44.

95. Carlezon Jr, WA Mague SD, Andersen SL. Enduring behav-ioral effects of early exposure to methylphenidate in rats.Biol Psychiatry 2003;54(12):1330-7.

96. Andersen SL, Navalta CP. Altering the course ofneurodevelopment: a framework for understanding the en-during effects of psychotropic drugs. Int J Dev Neurosci2004;22(5-6):423-40.

97. Joshi SV. ADHD, growth deficits, and relationships topsychostimulant use. Pediatr Rev 2002;23(2):67-8; discus-sion 67-8.

98. Spencer T, Biederman J, Wilens T. Growth deficits inchildren with attention deficit hyperactivity disorder. Pediat-rics 1998;102(2 Pt 3):501-6.

99. Klein RG, Landa B, Mattes JA, et al. Methylphenidate andgrowth in hyperactive children. A controlled withdrawalstudy. Arch Gen Psychiatry 1988;45(12):1127-30.

00. Klein RG, Mannuzza S. Hyperactive boys almost grown up.III. Methylphenidate effects on ultimate height Arch GenPsychiatry 1988;45(12):1131-4.

01. Safer D, Allen R, Barr E. Depression of growth in hyperac-tive children on stimulant drugs. N Engl J Med1972;287(5):217-20.

02. Spencer TJ, Biederman J, Harding M, et al. Growth deficitsin ADHD children revisited: evidence for disorder-associatedgrowth delays? J Am Acad Child Adolesc Psychiatry1996;35(11):1460-9.

03. Barkley RA. The effects of methylphenidate on the interac-tions of preschool ADHD children with their mothers. J AmAcad Child Adolesc Psychiatry 1988;27(3):336-41.

04. Barkley RA, Karlsson J, Strzelecki E, et al. Effects of age andRitalin dosage on the mother-child interactions of hyperactivechildren. J Consult Clin Psychol 1984;52(5):750-8.

05. Byrne JM, Bawden HN, DeWolfe NA, et al. Clinical assess-ment of psychopharmacological treatment of preschoolers withADHD. J Clin Exp Neuropsychol 1998;20(5):613-27.

06. Cohen NJ, Sullivan J, Minde K, et al. Evaluation of therelative effectiveness of methylphenidate and cognitive be-havior modification in the treatment of kindergarten-agedhyperactive children. J Abnorm Child Psychol1981;9(1):43-54.

07. Conners CK. Controlled trial of methylphenidate in pre-school children with minimal brain dysfunction. Int J Ment
Health 1975;4:61-74.
29

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

3

08. Handen BL, Feldman HM, Lurier A, et al. Efficacy ofmethylphenidate among preschool children with develop-mental disabilities and ADHD. J Am Acad Child AdolescPsychiatry 1999;38(7):805-12.

09. Mayes SD, Crites DL, Bixler EO, et al. Methylphenidate andADHD: influence of age, IQ and neurodevelopmental status.Dev Med Child Neurol 1994;36(12):1099-107.

10. Musten LM, Firestone P, Pisterman S, et al. Effects ofmethylphenidate on preschool children with ADHD: cogni-tive and behavioral functions. J Am Acad Child AdolescPsychiatry 1997;36(10):1407-15.

11. Schleifer M, Weiss G, Cohen N, et al. Hyperactivity inpreschoolers and the effect of methylphenidate. Am J Ortho-psychiatry 1975;45(1):38-50.

12. Short EJ, Manos MJ, Findling RL, et al. A prospective studyof stimulant response in preschool children: insights fromROC analyses. J Am Acad Child Adolesc Psychiatry2004;43(3):251-9.

13. Firestone P, Musten LM, Pisterman S, et al. Short-term sideeffects of stimulant medication are increased in preschoolchildren with attention-deficit/hyperactivity disorder: a dou-ble-blind placebo-controlled study. J Child Adolesc Psycho-pharmacol 1998;8(1):13-25.

14. Barkley RA, McMurray MB, Edelbrock CS, et al. Sideeffects of methylphenidate in children with attention deficithyperactivity disorder: a systemic, placebo-controlled eval-uation. Pediatrics 1990;86(2):184792.

15. Kratochvil CJ, Greenhill LL, March JS, et al. The role ofstimulants in the treatment of preschool children with attention-deficit hyperactivity disorder. CNS Drugs 2004;18(14):957-66.

16. Abikoff HB. For the PATS Study Group. A placebo-controlled efficacy study of methylphenidate in ADHDPreschoolers. Presented at the annual meeting of the Amer-ican Academy of Child and Adolescent Psychiatry, Wash-ington, DC, October, 2004.

17. Greenhill LL, Swanson JM, Vitiello B, et al. Impairment anddeportment responses to different methylphenidate doses inchildren with ADHD: the MTA titration trial. J Am AcadChild Adolesc Psychiatry 2001;40(2):180-7.

18. Arnold LE, Abikoff HB, Cantwell DP, et al. National Instituteof Mental Health Collaborative Multimodal Treatment Study ofChildren with ADHD (the MTA). Design challenges andchoices. Arch Gen Psychiatry 1997;54(9):865-70.

19. Richters JE, Arnold LE, Jensen PS, et al. NIMH collabora-tive multisite multimodal treatment study of children withADHD: I. Background and rationale. J Am Acad ChildAdolesc Psychiatry 1995;34(8):987-1000.

20. American Academy of Pediatrics. Clinical practice guideline:treatment of the school-aged child with attention-deficit/hyper-activity disorder. Pediatrics 2001;108(4):1033-44.

21. Dulcan M. Practice parameters for the assessment andtreatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder. American Academy of Childand Adolescent Psychiatry. J Am Acad Child AdolescPsychiatry 1997;36(10 Suppl):85S-121S.

22. Sonuga-Barke EJ Thompson M, Abikoff HB, et al. Non-pharmacological interventions for preschool ADHD: Thecase for specialized parent training. Infants Young Child
2005 (in press).
0

23. Greenhill LL, Jensen PS, Abikoff H, et al. Developing strategiesfor psychopharmacological studies in preschool children. J AmAcad Child Adolesc Psychiatry 2003;42(4):406-14.

24. Vitiello B. Psychopharmacology for young children: clinicalneeds and research opportunities. Pediatrics 2001;108(4):983-9.

25. Hechtman L, Abikoff H, Klein RG, et al. Academic achieve-ment and emotional status of children with ADHD treatedwith long-term methylphenidate and multimodal psychoso-cial treatment. J Am Acad Child Adolesc Psychiatry2004;43(7):812-9.

26. Slomkowski C, Klein RG, Mannuzza S. Is self-esteem animportant outcome in hyperactive children? J Abnorm ChildPsychol 1995;23(3):3037–15.

27. Strayhorn JM, Weidman CS. Reduction of attention deficitand internalizing symptoms in preschoolers through parent-child interaction training. J Am Acad Child Adolesc Psychi-atry 1989;28(6):888-96.

28. Hartman RR, Stage SA, Webster-Stratton C. A growth curveanalysis of parent training outcomes: examining the influenceof child risk factors (inattention, impulsivity, and hyperac-tivity problems), parental and family risk factors. J ChildPsychol Psychiatry 2003;44(3):388-98.

29. Pisterman S, McGrath P, Firestone P, et al. Outcome ofparent-mediated treatment of preschoolers with attentiondeficit disorder with hyperactivity. J Consult Clin Psychol1989;57(5):628-35.

30. Webster-Stratton C, Reid MJ, Hammond M. Treating chil-dren with early-onset conduct problems: intervention out-comes for parent, child, and teacher training. J Clin ChildAdolesc Psychol 2004;33(1):105-24.

31. Bor W, Sanders MR, Markie-Dadds C. The effects of the TripleP-Positive Parenting Program on preschool children with co-occurring disruptive behavior and attentional/hyperactive diffi-culties. J Abnorm Child Psychol 2002;30(6):571-87.

32. Sonuga-Barke EJ, Daley D, Thompson M, et al. Parent-basedtherapies for preschool attention-deficit/hyperactivity disorder: arandomized, controlled trial with a community sample. J AmAcad Child Adolesc Psychiatry 2001;40(4):402-8.

33. Sonuga-Barke EJ, Thompson M, Daley D, et al. Parenttraining for Attention Deficit/Hyperactivity Disorder: is it aseffective when delivered as routine rather than as specialistcare? Br J Clin Psychol 2004;43(4):449-57.

34. Barkley RA, Shelton TL, Crosswait C, et al. Multi-methodpsycho-educational intervention for preschool children withdisruptive behavior: preliminary results at post-treatment.J Child Psychol Psychiatry 2000;41(3):319-32.

35. Sonuga-Barke EJ, Daley D, Thompson M. Does maternalADHD reduce the effectiveness of parent training for pre-school children’s ADHD? J Am Acad Child Adolesc Psy-chiatry 2002;41(6):696-702.

36. McGoey KE, Eckert TL, DuPaul GJ. Early intervention forpreschool-age children with ADHD: a literature review. JEmotion Behav Disord 2002;10(1):14-28.

37. Cunningham CE, Bremner R, Boyle M. Large group com-munity-based parenting programs for families of preschool-ers at risk for disruptive behaviour disorders: utilization, costeffectiveness, and outcome. J Child Psychol Psychiatry
1995;36(7):1141-59.

Diagnosis and management of attention-deficit/hyperactivity disorder in children, young people, and...

Documents

Transcript of Diagnosis and management of attention-deficit/hyperactivity disorder in children, young people, and...