International Review of Psychiatry, April 2008; 20(2): 143–149

Beyond the ‘typical’ patient: Treating attention-deficit/hyperactivity
disorder in preschoolers and adults
BRIGETTE S. VAUGHAN, MARTIN W. WETZEL, & CHRISTOPHER J. KRATOCHVIL
Department of Psychiatry, University of Nebraska Medical Center, Omaha, NE, USA
Abstract
Attention-deficit/hyperactivity disorder (ADHD), typically affects school-aged children, but can present during the
preschool years and persist into adulthood. Accurate diagnosis for preschoolers and adults requires adaptation of the current
diagnostic criteria to account for differences in symptomatology across the age span. The differential diagnosis of
ADHD and the pattern of psychiatric comorbidity vary with each age group and complicate diagnosis and management.
To maximize outcomes clinicians must be able to accurately identify ADHD across the lifespan, and develop comprehensive,
collaborative treatment plans. The Preschool ADHD Treatment Study (PATS) demonstrated the potential utility of
methylphenidate for treating ADHD in preschoolers, and trials of psychostimulants and atomoxetine have shown some
benefits for adults. Behavioural interventions likely have an adjunctive role in ADHD treatment for both groups.
More research, however, is needed to determine the safest and most effective pharmacotherapies and psychosocial
interventions for these non-typical patients.
Introduction/epidemiology
Attention-deficit/hyperactivity disorder (ADHD) is a
highly heritable neurobehavioural disorder, with
onset before age 7 (American Psychiatric
Association, 2000). Although most commonly
identified between ages 7 and 10 years, ADHD
symptoms and impairment often emerge as early as
age 3 (Lavigne et al., 1996) and frequently
persist into adulthood. Epidemiological surveys of
community samples indicate that 2–6% of preschoo-
lers meet diagnostic criteria for ADHD (Angold,
Erkanli, Egger, & Costello, 2000; Lavigne et al.,
1996), with prevalence rates in school-aged children
conservatively estimated at 3 to 7% (American
Psychiatric Association, 2000). The prevalence
of ADHD decreases with age, affecting approxi-
mately 6% of adolescents and 3–4% of adults
(Fayyad et al., 2007).
Impairment
Appreciating the potential impairment from ADHD
in a preschooler may be difficult, however, three- to
five-year-old children with ADHD are at high risk for
academic, behavioural, social, and family dysfunc-
tion (DuPaul, McGoey, Eckert, & Van Brakle,
2001). These young children are more likely to be
placed in special education programs and have more
overall academic impairment (Lahey et al., 2004;
Lahey et al., 1998). Preschool ADHD has also been
correlated with increased risk for accidents and
injuries (Lahey et al., 1998), parent-reported aggres-
sive behaviours (Connor et al., 2003), teacher-
reported social and classroom behaviour problems,
and internalizing symptoms (Cunningham & Boyle,
2002).
Despite the historically limited awareness of the
persistence of ADHD into adulthood, the impair-
ment can be significant in this group as well (Kessler
et al., 2006). Adults with ADHD have been shown in
multiple studies to have diminished rates of college
graduation, and more occupational/vocational diffi-
culties, motor vehicle accidents, legal problems,
unplanned pregnancies, relationship problems,
smoking and substance abuse (Barkley, 2006).
Phenomenology
The same criteria for diagnosing ADHD are used
with a 5-year-old, 10-year-old, and a 50-year-old,
leaving the clinician to apply them in a developmen-
tally appropriate way. Without age-specific criteria,
evaluating children younger than 6, older adoles-
cents, and adults, can be challenging. Young
children frequently present with predominantly
hyperactive symptoms (Hardy, Kollins, Murray, &
al, 2007), while elementary-age children commonly
Correspondence: Christopher Kratochvil, MD, Department of Psychiatry, 985581 Nebraska Medical Center, Omaha, NE 68198-5581, USA.
Tel: 402 552 6005. Fax: 402 552 6247. E-mail: ckratoch@unmc.edu
ISSN 0954–0261 print/ISSN 1369–1627 online ß 2008 Informa UK Ltd.
DOI: 10.1080/09540260801887751
have a combination of inattention, hyperactivity and
impulsivity. Hyperactivity and impulsivity become
less prominent after puberty (Krause, Krause,
Dresel, la Fougere, & Ackenheil, 2006), and adults
with ADHD may present in partial remission
(Kessler et al., 2006). Clinicians must recognize
that even without a sufficient number of symptoms to
meet full DSM-IV criteria for ADHD, the presenting
symptoms and resulting impairment may still be
significant, particularly for adults.
Co-occurring conditions
Preschool ADHD is frequently comorbid with other
psychiatric conditions. At least one additional
disorder was identified in 74% of a clinically referred
preschool sample (Wilens et al., 2002). Language
problems (Posner et al., 2007), developmental
coordination disorder (Kadesjo & Gillberg, 1998),
and underachievement in reading and math (Lahey
et al., 1998) are common in young children with
ADHD. Psychiatric comorbidities were identified in
64% of preschoolers with ADHD in a community
sample, with conduct disorder and generalized
anxiety disorder being most common (35%), fol-
lowed by oppositional defiant disorder (6.8%),
depression (5.2%), social phobia (1%)
and separation anxiety disorder (0.9%) (Egger &
Angold, 2004).
In the National Comorbidity Survey Replication,
rates of co-occurring psychiatric disorders were
nearly 3 times higher in adults with ADHD than in
those without: 38.3% had a co-occurring mood
disorder, 47.1% an anxiety disorder, and 15.2%
a substance abuse disorder (Kessler et al., 2006).
Clinical challenges
ADHD is a clinical diagnosis based primarily on
patient interviews and collateral information. While
there are no standardized, validated technologies
or testing procedures for diagnosing ADHD, multi-
ple tools are available to supplement the clinical
assessment. Screening instruments and rating scales,
many available at no cost (Table I), are efficient
means of identifying symptoms. Symptom checklists
alone, however, are insufficient, as those commonly
used in school age children may over-identify ADHD
in a preschooler (Gimpel & Kuhn, 2000), or under-
diagnose it in an adult (Faraone et al., 2006).
While the evidence-base for the treatment of
ADHD in grade school children is extensive, data
supporting treatments for preschoolers and adults
is limited. This may partially explain why many
preschool children and adults with ADHD don’t
receive care. In a community study only 19% of
children with a preschool-onset behaviour disorder
received services (Pavuluri, Luk, & McGee, 1996)
and less than 20% of adults with ADHD were
reported as diagnosed or treated (Newcorn, Weiss, &
Stein, 2007).
Early onset ADHD also requires clinicians to
balance the potential benefits of early identification
and intervention with the risks of over-identification
and potential use of non-FDA approved pharma-
cotherapies. Managing adult ADHD requires clinical
competency in identifying comorbid disorders and
utilizing a class of medications not traditionally
prescribed in adult psychiatry (Kessler et al., 2006).
Despite the relative limitations of existing research,
data regarding the efficacy and safety of ADHD
treatments in preschoolers and adults is growing.
Preschool ADHD Treatment Study (PATS)
Prior to the NIMH-funded Preschool ADHD
Treatment Study (PATS), less than a dozen
placebo-controlled trials of psychostimulants
(all immediate-release methylphenidate) had been
conducted in this age group, (Kratochvil, Greenhill,
March, Burke, & Vaughan, 2004). Efficacy of
stimulant medication in the preschool age group
has been variable (Connor, 2002) and side effect
reports are increased (e.g. sadness, irritability,
clinginess, insomnia and anorexia) (Firestone,
Musten, Pieterman, Merecer and Bennett, 1998).
As a result, medication has historically been used
in only the most severe preschool cases or when
parent training and structured educational settings
are not adequate or available (Dulcan, 1997).
The PATS study assessed the safety and efficacy of
methylphenidate in preschoolers ages 3 to 5.5 years
(Greenhill et al., 2006). This 8-phase, 70-week
study recruited 303 children. ADHD severity and
impairment were significant, and comorbidity was
frequent with 70% of subjects having at least one
co-occurring diagnosis (Riddle, 2007). Eligible
families completed a 10-week group parent training
programme. Children with less than a 30%
Table I. Public Domain ADHD Rating Scales.
Pediatric ADHD Rating Scales
. Vanderbilt ADHD Diagnostic Parent Rating Scale:
http://www.vanderbiltchildrens.com/uploads/documents/ccdr_
adhd_scale.pdf
. SNAP-IV Rating Scale Revised: http://www.adhd.net/
Adult ADHD Rating Scales
. Adult Self Report Scale v1.1: http://www.hcp.med.harvard.edu/
ncs/asrs.php
. Canadian ADHD Resource Alliance Adult ADHD Assessment:
http://www.caddra.ca
. Wender Utah Rating Scale: http://www.medalreg.com/www/
xdocs/docs_ch18/doc_ch18.12.html
144 B. S. Vaughan et al.
improvement in ADHD symptom severity following
parent training were eligible for the methylphenidate
treatment phase. One-hundred and sixty-five
preschoolers were randomized in the double
blind placebo-controlled titration phase of PATS.
Methylphenidate demonstrated short term efficacy
for reducing ADHD symptoms, with a graduated
dose-response (Greenhill et al., 2006). The mean
best total daily dose of methylphenidate for the
group was 14.2 Æ8.1 mg/day (0.7Æ0.4 mg/kg/day),
significantly lower than the 30 mg/day reported for
school-aged children in the Multimodal Treatment
Study of Children with ADHD (MTA) (MTA
Cooperative Group, 1999). Although ADHD symp-
toms were significantly reduced on 2.5 mg, 5 mg,
and 7.5 mg given TID compared to placebo, effect
sizes observed in preschoolers (0.16–0.72) were
smaller than those found in school-aged children
on methylphenidate (Greenhill et al., 2006).
Statistically but not clinically significant elevations
of blood pressure and pulse were observed with
methylphenidate treatment. During the year of
methylphenidate treatment in PATS, children
gained less weight (À1.32 kg/year) and grew more
slowly (À1.38 cm/year) than predicted from their
baseline measurements (Swanson et al., 2006).
This was consistent with growth rate reductions
seen in school-age children in the MTA study
(National Institute of Mental Health, 2004). The
most frequently reported adverse events in PATS
were emotional outbursts, difficulty falling asleep,
repetitive behaviours/thoughts, appetite reduction
and irritability. Twenty-one children (11%) discon-
tinued due to adverse events, although no
drug related serious adverse events were reported
(Wigal et al., 2006).
Preliminary pharmacokinetic data from PATS
demonstrated that clearance of a single dose of
MPH in preschoolers takes longer than the same
dose by weight given to school-aged children
(p¼0.0002), suggesting that younger children may
respond at lower doses with less frequent adminis-
tration. Starting at lower doses may also improve
tolerability of methylphenidate for younger, smaller
patients (Wigal et al., 2007).
Atomoxetine in young children
No controlled studies of non-stimulant medications
for young children with ADHD have been completed
to-date. Twenty-two 5- and 6-year-old children with
ADHD were treated with flexibly-dosed atomoxetine
(maximum 1.8 mg/kg/day) in an 8-week open-label
study (Kratochvil et al., 2007). Significant decreases
were observed on the ADHD-IV-RS-Parent
total and inattentive and hyperactive/impulsive sub-
scale scores (p50.001). The mean final daily dose of
atomoxetine was approximately 1.25 mg/kg/day,
in line with the typical target dose of 1.2 mg/kg/day.
There were no discontinuations due to adverse
events; however, 12 subjects (54.5%) reported
mood lability. Half of the subjects reported decreased
appetite, and a mean 1.04 kg weight loss was
observed for the group (p50.001).
Preschool psychosocial interventions
Parenting variables significantly impact behavioural
outcomes of preschool children with ADHD
(DuPaul, McGeoy, Eckert, & Van Brakle, 2001).
Negative, inconsistent parental behaviour and
high levels of family adversity are associated
with early onset and persistent behavioural
problems (Cunningham & Boyle, 2002), so directing
interventions at improving parenting skills may
positively affect child behaviour. Home-based
parent training was demonstrated to be effective
for reducing ADHD symptoms in preschool
children (Sonuga-Barke, Daley, Thompson,
Laver-Braudbury, & Weeks, 2001). Parent-child
interaction training was also shown to reduce
ADHD and internalizing symptoms (Strayhorn &
Weidman, 1989). Of the 261 subjects who com-
pleted parent training in PATS, only 7.2% had
significant improvement (Greenhill et al., 2006),
however, the severity of ADHD in these preschoolers
may have contributed to their being less responsive to
a psychosocial intervention alone. The long-term
benefit of parent training has not been demonstrated.
Practice parameters for managing
preschool ADHD
The American Academy of Child and Adolescent
Psychiatry (Dulcan, 1997) and the American
Academy of Pediatrics (American Academy of
Pediatrics, 2001) have developed practice guidelines
for the evaluation and treatment of pediatric ADHD.
A thorough and systematic assessment of the child
using reports from parents, caregivers and teachers
is recommended (Dulcan, 1997). Standardized
rating scales (e.g. Conners’ Rating Scales, DuPaul’s
ADHD-IV Rating Scale) can be used to identify
target symptoms and document baseline severity.
Reports of psychoeducational testing, academic
performance, and current individualized educational
plans (IEPs) or behavioural plans should be
reviewed. The child’s mental status, cognitive and
speech/language abilities, and fine/gross motor skills
should be assessed and a physical exam with screen-
ing for possible visual and/or auditory deficits
conducted. Comorbid learning disabilities, mental
retardation, developmental delays, or other psychia-
tric disorders should be identified or ruled out prior
Treating attention-deficit/hyperactivity disorder in preschoolers and adults 145
to initiation of treatment. In the case of a young
child, the clinician needs to also rule out possible
abuse. Performance across settings (classroom, peer
group, family) should be assessed and monitored
(Dulcan, 1997).
Treatments should be selected based on target
symptom severity, comorbidities, family preferences
and ability to implement, as well as access to
services (American Academy of Pediatrics, 2001)
and educational placement (Dulcan, 1997). Prior to
initiating medication, it is generally recommended
to increase structure at home and school, and
implement behavioural modification and parent
training interventions. While maintaining
structure and consistently implementing an effective
behaviour management programme is challenging,
parent and teacher satisfaction with ADHD treat-
ment has been shown to increase when behaviour
therapy is used alone or along with medication
(American Academy of Pediatrics, 2001). Parent
training, education, and support (Table II) can
improve parent-child interactions and increase com-
pliance (Dulcan, 1997).
If indicated, medication should be initiated at low
doses, titrated slowly, and monitored frequently.
Methylphenidate is a first-line treatment for ADHD,
and the pharmacotherapy with the most data in
young children with ADHD. Given the pervasive
effects of ADHD, administering medication 7 days
per week is recommended (Dulcan, 1997). During
treatment, children should be seen in the clinic at
least every 3 to 6 months to monitor treatment
effectiveness and tolerability, compliance, vital signs,
growth parameters, as well as any significant changes
at home or school (American Academy of Pediatrics,
2001). A combination of long and short-acting
preparations may be used to optimally manage the
child’s individual symptoms; however, this strategy
has not been specifically examined in young children.
Management of adult ADHD
While a consensus treatment guide for managing
adult ADHD is not currently available, many of the
principles used for children can be applied, and
issues such as access to resources and services, and
ability to comply with treatment remain relevant.
A collaborative treatment plan identifying target
symptoms and specific goals should be established
at the time of diagnosis.
As of 2007, extended release d-methylphenidate,
extended release mixed amphetamine salts, and
atomoxetine are approved by the US Food and
Drug Administration (FDA) for the treatment of
ADHD in adults. Considerable evidence demon-
strating the efficacy of psychostimulants in treating
adults with ADHD is available (Asherson, 2005).
Atomoxetine has also been demonstrated in double
blind, placebo controlled studies to be an effective
treatment for adults (Buitelaar et al., 2007). As with
children, full-day symptom control for adults using
stimulants may require multiple doses or combina-
tions of long and short-acting agents. Atomoxetine
can generally be dosed once daily, depending on
tolerability and duration of effect. Clinicians
and patients should be aware that compared to
stimulants, benefits may be slower in onset with
atomoxetine.
Prior to beginning pharmacotherapy clinicians
should obtain a comprehensive medical history
with particular attention to cardiovascular disease,
hypertension, glaucoma, and family history of early
or sudden death (Food and Drug Administration,
2004). A physical exam with baseline weight,
blood pressure, and pulse is generally adequate,
and unless indicated by history, no laboratory,
ECG, or neuropsychological testing is required.
Patients should be monitored closely after starting
medication.
Common side effects from psychostimulants in
adults are anorexia, weight loss, insomnia, head-
aches, stomach pain, and irritability. These are often
temporary, and managed with dose or medication
changes. Minor but statistically significant changes
in pulse and blood pressure occurred in clinical trials
(Wilens et al., 2005); however, adults with normal
pre-treatment vital signs experienced minimal long-
term cardiovascular effects (Weisler et al., 2005).
Monitoring for changes is important, nonetheless.
Serious cardiovascular events including sudden
death have been reported in patients with pre-
existing cardiac problems or defects (Food and
Drug Administration, 2007). Additionally, adults
should be assessed for development of psychotic or
manic symptoms, and medication abuse.
Atomoxetine’s most common side effects in adults
are constipation, dry mouth, nausea, decreased
appetite, dizziness, sleep problems, sexual side
effects, problems urinating, and menstrual cramps
(Eli Lilly & Co., 2005). Patients should be monitored
for cardiovascular changes, liver injury, and
Table II. ADHD Resources for Patients and Families.
. ADHD Parents Med Guide: ParentMedGuide.org
. Children and Adults with Attention Deficit Hyperactivity
Disorder: www.chadd.org
. NIMH: National Institute of Mental Health (NIMH) Home
Page: www.nimh.nih.gov
. National Resource Center on AD/HD: A Program of CHADD:
www.help4adhd.org
. Attention Deficit Disorder Association - Adult ADD Resources,
Help, Information, and Support: http://www.add.org
. American Academy of Child & Adolescent Psychiatry:
www.aacap.org
146 B. S. Vaughan et al.
development of psychosis, mania or suicidal ideation.
Over time, dose adjustments for symptomatic
management may be warranted due to changes in
metabolism, psychosocial environments, concomi-
tant medications, health status (e.g. cardiovascular
disease), and cognitive changes associated with
normal aging (Gazzaley et al., 2005).
Pharmacotherapy alone may not be sufficient for
adults as effect sizes for atomoxetine and psychosti-
mulants at FDA-approved doses are approximately
half those seen in children (Newcorn et al., 2007).
Cognitive-behavioural therapy has been shown to be
an effective augmentation to medication for adults
with ADHD (Safren, 2006). Counseling, lifestyle
changes (e.g. reducing caffeine intake, exercising
regularly, maintaining daily routine and organiza-
tional system), and work environment changes
may reduce ADHD related emotional distress
(Hallowell & Ratey, 2006). Many areas of the USA
also have support groups for adults with ADHD.
Conclusion
ADHD can be an impairing disorder at any age.
It frequently co-occurs with other psychiatric
disorders, and if left untreated, can result in
significant academic, occupational, social and
family dysfunction. While studies of school-aged
children have generally guided the use of stimulants
in preschoolers, the limited safety and efficacy
information on acute and long-term effects of these
medications in preschoolers can make decisions
regarding initiating and managing pharmacotherapy
difficult. Methylphenidate appears to be moderately
effective in the short-term for preschoolers with
ADHD, but data evaluating dosing extended-release
formulations and the long-term effects of early
pharmacotherapy are needed. Additional research
on parent training and school-based interventions
is needed to determine which children may most
likely benefit from them, how they compare with
medication, and their potential augmentative value
to pharmacotherapy.
Identifying and managing ADHD in adults
may require clinicians to incorporate new clinical
knowledge into their practice. Properly diagnosing
adult ADHD requires a comprehensive mental
health evaluation. Medications and counselling
have proven safe and effective for adults; however,
management of adult ADHD also requires ongoing
support and education. Collaborating with patients
enhances treatment response and reduces barriers
ADHD imposes on optimal function. Additional
research is needed to determine the interaction of
the normal aging process and ADHD, and the
most effective treatments for affected adults.
Our understanding of this chronic and impairing
disorder in non-typical patients is growing and
research into treatment options is encouraging.
Acknowledgements
Dr Kratochvil is supported by NIMH Grant
5K23MH06612701A1. He also receives grant
support from Eli Lilly, McNeil, Shire, Abbott,
Pfizer and Cephalon, is a consultant for Eli Lilly,
AstraZeneca, Abbott and Pfizer, and a member of
the Eli Lilly speaker’s bureau. He receives study drug
for an NIMH-funded study from Eli Lilly.
No industry or grant support was received for
preparation of this manuscript.
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