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hyperactivity
disorder in children
The right clinical information, right where it's needed
Basics 4
Definition 4
Epidemiology 4
Aetiology 4
Pathophysiology 5
Classification 6
Prevention 8
Primary prevention 8
Screening 8
Secondary prevention 8
Diagnosis 9
Case history 9
Step-by-step diagnostic approach 9
Risk factors 11
History & examination factors 12
Diagnostic tests 15
Differential diagnosis 16
Diagnostic criteria 23
Treatment 26
Step-by-step treatment approach 26
Treatment details overview 30
Treatment options 32
Emerging 51
Follow up 52
Recommendations 52
Complications 52
Prognosis 54
Guidelines 55
Diagnostic guidelines 55
Treatment guidelines 55
Online resources 57
Evidence scores 58
References 59
Disclaimer 71
Summary
◊ Some impairment must be present by 12 years of age and 60% to 70% of patients have persistent
functional impairment into adulthood.
◊ Diagnosed by clinical history, which should include information from multiple sources, including
parents, carers, and teachers.
◊ Mainstay of treatment is stimulant medication, which can be effective in 85% of patients; non-
stimulants are less often effective, but may have other advantages in terms of duration of action or in
special populations.
◊ Stimulant medications have been associated with cardiovascular side effects. These should be
monitored in children with heart conditions.
At tention deficit hyperactivity disorder in children Basics
Definition
ADHD is a problem of inattention, hyperactivity, and impulsivity according to the American Psychiatric
Association.[1] This disorder is recognised globally and is referred to as hyperkinetic disorder in Europe
BASICS
and other countries that use the WHO classification system.[2] ADHD is a chronic condition with symptoms
that begin in early childhood but often persist into adult life. A key element of the definition is functional
impairment across 2 or more domains, most often in school and at home.[1] As a result, ADHD can
limit academic, interpersonal, and occupational success and can also lead to greater risk-taking and
accidents.[3] In addition, patients with ADHD are more likely to have co-existing psychiatric disorders such as
oppositional defiant disorder (ODD), conduct disorder, substance abuse, and possibly mood disorders, such
as depression and mania.[4] [5] [6] [7] [8] [9]
Epidemiology
Prevalence: ADHD is one of the most common disorders of childhood. The global prevalence is around
5%.[12] In the US, the National Survey of Children's Health found an overall prevalence of 11% among
children aged 4 to 17 years in 2011,[13] while the National Health Interview Study found an estimated 8% of
US children aged 3 to 17 years had ADHD in 2010.[14]
Subtypes: the combined subtype accounts for 50% to 75% of all people with ADHD, the inattentive subtype
accounts for 20% to 30%, and the hyperactive-impulsive subtype accounts for 15%. Over time, inattentive
symptoms tend to persist and hyperactive-impulsive symptoms tend to diminish.[10]
Gender disparities: community studies such as the National Survey of Children's Health show male-to-female
prevalence rates of around 2.3 to 1, while clinic populations show the ratio as high as 10 to 1.[13] [15] This
gender difference has been explained by the fact that boys present more often with disruptive behaviour that
prompts referral, whereas girls more commonly have the inattentive type and have lower comorbidity with
ODD and conduct disorder.[10] [15]
Ethnic differences: several large studies suggest that Hispanic children have a lower prevalence of ADHD
than white or black American children.[13] [16] According to the Multimodal Treatment Study of AD/HD
(MTA), there were higher reported levels of ADHD in the classroom for African-American than Caucasian
children.[17] It is unclear if these findings represent actual prevalence differences or whether they may be
related to confounding variables such as access to care.
Class differences: ADHD has been associated with poverty, lower family income, and lower social class in
the US, the UK, and other countries.[18]
Aetiology
The aetiology of ADHD is probably multifactorial and composed of genetic and environmental factors.
Genetic predisposition: there is substantial evidence for a genetic contribution to ADHD, with the mean
heritability for ADHD shown to be 76% based on twin studies.[19] Some propose that several genes interact
to cause the ADHD phenotype, while others see ADHD as the final common pathway for variant alleles.[3]
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At tention deficit hyperactivity disorder in children Basics
Linkage analysis examines the linkage between the disorder and evenly spaced DNA markers throughout the
entire genome.[20] Linkage data suggest that ADHD is associated with markers at chromosomes 4, 5, 6, 8,
11, 16, and 17.[21]
BASICS
Association analysis examines specific candidate genes based on known ADHD pathophysiology. A
statistically significant association with ADHD has been demonstrated in the genes coding for dopamine
4 and 5 receptors, the dopamine transporter, the enzyme dopamine beta-hydroxylase, the serotonin
transporter gene, the serotonin 1B receptor, and the synaptosomal-associated protein 25 gene.[19]
The development of powerful new tools for genetic analysis has allowed genome-wide association studies,
which may provide more focused data in the coming years.
Environmental factors: these account for 12% to 40% of the variance in twin ADHD scores.[22] Low
birth weight and maternal smoking have the strongest evidence for association with ADHD. Other risk
factors include poverty, lead exposure, iron deficiency, maternal alcohol drinking during pregnancy, and
psychosocial adversity.[10] [23] [24] Antenatal antidepressant use in mothers seems to be associated with
an increased risk of ADHD among offspring, but the risk also appears to be raised among children whose
mothers use antidepressants before conception and among those with psychiatric illness who did not use
antidepressants, suggesting that the increased risk can be at least partly explained by the pre-existing
maternal psychiatric condition.[25]
Pathophysiology
The pathophysiology of ADHD is rapidly evolving and there is not yet a unifying theory.
Brain neurochemistry: because up to 85% of ADHD patients respond to stimulants, the mechanism of action
of methylphenidate and amfetamine provides an important clue.[26] Stimulants increase the free brain levels
of norepinephrine and dopamine by blocking presynaptic neuronal reuptake and triggering release of these
neurotransmitters, suggesting that ADHD may result from a dysfunction of norepinephrine and dopamine.[27]
One proposed theory is that abnormal dopamine transporter density contributes to the disorder.[28] Another
is that the norepinephrine transporter,[29] and/or glutamate receptor,[30] and/or monoamine oxidase A
transporter[31] is involved. ADHD brain chemistry has also been linked to dysfunctions in the serotonergic
system.[31] [32]
Neuropsychology: executive dysfunction is common in ADHD and this has led to theories about dysfunction
in frontal-subcortical circuits, which mediate response inhibition, vigilance, and working memory.[33]
Brain structure: neuro-imaging studies have demonstrated that children with ADHD have reduced brain
volume in certain areas, including the cerebellum, the splenium of the corpus callosum, the total cerebrum,
the right cerebrum, the right caudate, sensorimotor brain regions, and various frontal regions.[34] [35]
These structural differences are only significant when comparing groups of patients with ADHD with normal
controls, so it is not possible to use neuro-imaging to diagnose ADHD in individual patients. There is
some evidence that stimulant therapy may be associated with normalisation of structural abnormalities in
ADHD.[36]
Brain function: functional neuro-imaging including single photon emission-CT (SPECT), functional magnetic
resonance imaging (fMRI), PET scan, and proton magnetic resonance spectroscopy (pMRS) studies
have demonstrated differences in children with ADHD, including reduced activation in the basal ganglia
and anterior frontal lobe,[37] and altered cortico-striatal-thalamic connectivity.[38] Another study showed
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At tention deficit hyperactivity disorder in children Basics
that children with ADHD had higher connectivity in the ventral striatum and orbitofrontal cortex, and lower
connectivity in the superior parietal cortex and precuneus networks.[39] The neuro-imaging literature on
ADHD is growing rapidly.[40]
BASICS
Classification
Classification of ADHD[1]
1. Predominantly hyperactive-impulsive type
In the predominantly hyperactive-impulsive type, preschool children are often taken to the doctor by
exhausted parents who describe the child as 'driven' or a 'bundle of energy'. These children will often have
difficulties physically controlling their behaviour. Presenting complaints include squirming rather than sitting,
running around, and interrupting. They often present because of disruptive behaviours in nursery school
when the routine (to queue up at the door) and verbal instructions (to work quietly at your desks) of the
classroom are difficult for them to follow. For diagnosis of predominantly hyperactive-impulsive type, the
patient must have 6 out of 9 of the following hyperactive-impulsive criteria (older adolescents and adults only
need to have 5 of 9 significant issues to meet diagnostic criteria):[1]
In the predominantly inattentive type, children often present later in childhood or adolescence with symptoms
such as failure to follow directions, making careless mistakes, forgetfulness, and difficulty organising tasks.
They often present because of academic difficulties and a teacher's concern that the student is not trying
or does not care about their required work. They may also be referred for possible absence epilepsy since
they appear to stare off or 'zone out'. For diagnosis of predominantly inattentive type, the patient must have 6
out of 9 of the following inattentive criteria (older adolescents and adults only need to have 5 of 9 significant
issues to meet diagnostic criteria):[1]
• Often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other
activities
• Often has difficulty sustaining attention in tasks or play activities
• Often does not seem to listen when spoken to directly
• Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the
workplace (not due to oppositional behaviour or failure to understand instructions)
• Often has difficulty organising tasks and activities
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At tention deficit hyperactivity disorder in children Basics
• Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as
school work or homework)
• Often loses things necessary for tasks or activities (e.g., toys, school assignments, pencils, books, or
tools)
BASICS
• Is often easily distracted by extraneous stimuli
• Is often forgetful in daily activities.
3. Combined type: meets criteria for both hyperactive and inattentive types
The combined type of ADHD is the most common form and is characterised by both hyperactive and
disruptive behaviour as well as difficulty sustaining attention.
4. Unspecified ADHD: significant impairment but does not meet full criteria
In unspecified ADHD, children have significant functional impairment but do not meet full DSM-5 (Diagnostic
and statistical manual of mental disorders, 5th edition) criteria for ADHD: for instance, if the behaviours occur
in only 1 setting or if children meet fewer than 6 of the required DSM-5 criteria. These children often benefit
from treatment.
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At tention deficit hyperactivity disorder in children Prevention
Primary prevention
As the pathophysiology of ADHD is thought to have a strong genetic component, primary prevention is
difficult to undertake. However, parents can control environmental risk factors such as maternal smoking
during pregnancy, maternal alcohol use during pregnancy, and lead exposure at home. There are conflicting
data regarding whether omega-3 fatty acids have a positive effect on ADHD symptoms.[54] [55] [56] [57]
Using helmets for sport including bicycle riding can help reduce the risk of traumatic brain injury. On a
broader societal level, ever-higher academic expectations may cause children stress at increasingly younger
ages when they are less developmentally able to attend and focus. Parents and teachers can teach children
how to keep a planner to keep track of their work, work on homework together, and integrate extracurricular
activities such as sports, which channel hyperactivity productively. Maintaining positive self-esteem by setting
reasonable expectations and nurturing areas of academic and extra-curricular strength is critical.
Screening
Screening recommendations vary depending on the clinical setting. The American Academy of Pediatrics
recommends that the primary care clinician should initiate an evaluation for ADHD for any child from 4
to 18 years of age who presents with academic or behavioural problems and symptoms of inattention,
PREVENTION
hyperactivity, or impulsivity; the American Academy of Child and Adolescent Psychiatry practice parameters
recommend that screening for ADHD should be part of every patient's mental health assessment.[21]
That is, questions to assess the major symptoms of ADHD (including inattention, hyperactivity, and
impulsivity) should be asked regardless of presenting complaint when patients are undergoing mental health
assessments.
Clinicians should be aware that the presenting symptom in preschoolers is often hyperactivity, while
inattention is more prevalent among adolescents with ADHD.
Secondary prevention
Secondary prevention in ADHD focuses on the prevention of recurrence or exacerbation of ADHD symptoms
as the child develops. The physician should regularly assess functioning in multiple domains (including
academic performance, mood, anxiety, acting out behaviour, self-esteem). Behaviour assessment should
take place with clinical interviews with the patient, parent, and potentially teachers. If the child is growing,
then medication doses may need to be increased to maintain the same level of efficacy. Medication non-
compliance is more the rule than the exception, and this will have to be addressed in an ongoing way.
Particular attention should be paid to subtle side effects that may make medication unacceptable; these
can sometimes be ameliorated by dose adjustment or switching to another delivery system. However, non-
adherence can also derive from lack of understanding of the goals of treatment or a philosophical rejection of
medication; this requires a strong therapeutic partnership with patient and family, and increased knowledge
of the disorder. Psychoeducation is a very important aspect of successful long-term treatment as it is helpful
to anticipate the developmental challenges children with ADHD face as they enter adolescence and young
adulthood.[21]
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At tention deficit hyperactivity disorder in children Diagnosis
Case history
Case history #1
A 7-year-old boy is brought to the doctor because of academic difficulty at school and behavioural
problems that first came to attention in preschool when the teacher was concerned about impulsive
aggression. His mother reports that at home he runs around all day, needs multiple requests to pick up
his toys, and can only sit still for a few seconds before 'growing bored'. A teacher's note states that he
jumps queues, distracts his classmates, and loses his homework assignments, but appears bright and
is able to finish his work when he is given individual supervision. His mother is concerned because other
children are teasing him for being stupid. However, she reports that he is a sweet and motivated boy who
does not talk back to teachers or adults and does not bully anybody. In the surgery, he is jumping up and
down in the chair despite multiple requests by his mother to sit still. She notes that his 15-year-old brother
was also hyperactive when he was younger and has persistent academic problems.
Case history #2
A 12-year-old girl presents to her general practitioner because of problems with school performance.
She attends a large school, and her teacher has reported that she has not been turning in her homework
and she is falling behind in maths. Her father hired a tutor and she seems to respond well to individual
instruction, but cannot apply the lessons learned at school. In the surgery, it is noted that she is sitting
calmly but is constantly fiddling with her mobile phone and is distracted by the toys in the room. She says
that she does fine on tests but has difficulty focusing on homework. She still maintains an active social life
and reports that her mood is fine.
Other presentations
Presenting symptoms of ADHD change in character over the lifespan, with hyperactive symptoms
prominent at younger ages, and inattentive symptoms more common in adolescents and adults.[10]
DIAGNOSIS
Atypical presentations include newly recognised symptoms in teens and adults. All subtypes are
associated with comorbid diagnoses, including oppositional defiant disorder (ODD) in up to 54% to 84%
of children and adolescents with ADHD, conduct disorder, smoking in 15% to 19% of patients, other
substance abuse, learning or language problems in 25% to 35% of patients, and mood disorders such
as depression and mania.[4] [5] [6] [7] [10] [11] Of note, girls more commonly have the inattentive type
and have lower comorbidity with ODD and conduct disorder.[10] Across all subtypes, there are common
associated symptoms, including irritability, boredom, and difficulty with peer interactions.
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At tention deficit hyperactivity disorder in children Diagnosis
History
ADHD is a diagnosis made by clinical history that assesses behaviour in different areas of the child's
life.[21]
• Source of history: parent and patient history should be supplemented by history from teachers and
other carers such as coaches, tutors, or counsellors. This should include narrative history (including
learning patterns and peer interactions), grades, and rating scales. ADHD is more common in
males. Problems can include school absences, academic failure, disruptive behaviours, inattention,
and poor peer interactions. ADHD rating scales are important in eliciting history, but broadband
behaviour checklists can help to identify comorbid conditions. Some symptoms causing impairment
must be present before 12 years of age.[1]
• Focus of history: core symptoms of ADHD (specifically, the DSM-5 criteria), with attention to the
age of onset, degree of impairment, and settings in which the symptoms occur.[1] It is important
to note that symptoms vary significantly across settings and activities, becoming more prominent
when the child is doing activities they perceive as boring or challenging (e.g., school work), and
less prominent when doing activities they are more engaged with (e.g., video games).
• Symptom history: this is elicited with open-ended questions and commonly used rating scales.
• Family history: this includes history of ADHD, substance use, and other psychiatric illnesses.
• Developmental history: includes information about pregnancy (maternal smoking, alcohol, and
stress), birth history (including birth weight), and developmental milestones.
• Past medical history: including any CNS trauma or infections as well as current medications.
Possible lead exposure should be considered.
• Psychosocial history: including tensions in the home (between parents, between parent and child)
as well as detail regarding peer relationships, which are often impaired.
• Past psychiatric history: including past diagnoses and trauma history as well as assessment for
comorbid psychiatric disorders including oppositional defiant disorder (ODD), conduct disorder,
learning disabilities, mood disorders, and anxiety disorders.
The MSE should be performed as part of the diagnostic evaluation.[21] It includes appearance, alertness
and orientation, ability to relate with the interviewer, speech, mood and affect, thought process, and
estimation of cognitive ability. The MSE can assess for overt signs of ADHD including motor restlessness
or hyperactivity, inattention, and working memory impairment. Additionally, it can elicit information about
comorbid diagnoses as well as other mental disorders that would better explain the presenting symptoms.
It is important to note that patients may often appear calm, quiet, and attentive in the structured, one-
to-one setting of the doctor's surgery, and thus clinical presentation in this circumstance is not well
correlated with diagnosis.
Neuropsychological tests
Because ADHD is considered a behavioural disorder, neuropsychological testing is not necessary for
the diagnosis.[21] However, testing should be considered in cases in which it is important to differentiate
between ADHD and learning disabilities (e.g., dyslexia, non-verbal learning disability), and disorders of
language, visual-motor, or auditory processing. Failing to recognise a co-existing learning disability can
result in inadequate response to medication, school failure, and low self-esteem.
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At tention deficit hyperactivity disorder in children Diagnosis
In neuropsychological testing, patients with ADHD will generally have normal cognitive ability and
academic achievement but will exhibit deficits in executive functions (those required to plan, prioritise,
attend to, and inhibit behaviours) such as short-term (i.e., working) memory and processing speed
(the rate at which information is dealt with).[58] [59] Common tests of executive function include the
Continuous Performance Test, Wisconsin Card Sorting Test, and Digits Backward test. If a learning
disorder or a disorder of language, visual-motor, or auditory processing is suspected, appropriate
neuropsychological testing can assess impairment in these areas.
Laboratory/neurologicaltesting
Neither laboratory nor neurological testing is necessary in the work-up for ADHD if the medical history
is unremarkable.[21] Some medical conditions can mimic the symptoms of ADHD; these include
sleep disorders, traumatic brain injury, encephalopathy, lead exposure, or thyroid disorder. If these are
suspected, specific tests should be ordered according to the medical condition and patients may be
referred to the appropriate specialists.
Cardiovascular testing
Children with pre-existing heart disease, symptoms suggestive of heart disease (e.g., syncope,
palpitations, chest pain, post-exercise symptoms) or a strong family history for sudden death should be
referred to a cardiologist for examination before a stimulant trial. If patients develop any cardiac adverse
effects on stimulants, they should also be referred to a cardiologist. There is no need to obtain routine
ECGs or echocardiograms on healthy patients receiving stimulants.
Risk factors
Strong
family history of ADHD
• There is substantial evidence for a genetic predisposition for ADHD, with the mean heritability for
DIAGNOSIS
ADHD shown to be 76% based on twin studies.[19]
male gender
• Community studies such as the National Survey of Children's Health show male-to-female prevalence
rates of around 2.3 to 1, while in clinic populations the ratio has been shown to be as high as 10 to
1.[13] [15]
epilepsy
• Children with epilepsy are at increased risk for cognitive and behavioural disorders including
ADHD. While the reported prevalence rates vary depending on study population and methods of
determining the problem, clinical-based studies commonly report ADHD in 25% to 40% of children with
epilepsy.[44] While there can be contributions from persistent seizures and/or medication, one large
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At tention deficit hyperactivity disorder in children Diagnosis
study of childhood absence epilepsy found that 36% of the newly diagnosed cohort exhibited attention
deficits despite otherwise intact neurocognitive functioning.[45]
Weak
maternal alcohol use during pregnancy
• A study found a 2.5-fold increased risk for ADHD associated with antenatal exposure to alcohol.[42]
psychosocial adversity
• Rutter's study of families in the Isle of Wight yielded 6 risk factors that correlated with childhood mental
disturbance, and a positive association between Rutter's index of adversity and ADHD has been
demonstrated.[47] [48] [49] These factors include severe marital discord, low social class, large family
size, paternal criminality, maternal mental disorder, and foster placement. Another study has also
found that lower social class increased risk of hyperactive-impulsive symptoms but not inattentive
symptoms.[18]
lead exposure
• A dose-response relationship between lead exposure and ADHD has been demonstrated.[50]
DIAGNOSIS
iron deficiency
• Several studies have suggested iron deficiency may be a risk factor in the development of ADHD.[23]
[53]
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At tention deficit hyperactivity disorder in children Diagnosis
• Key risk factors include: FHx ADHD, low birth weight, maternal smoking during pregnancy, and male
gender.
does not follow through on instructions and fails to finish school work,
chores, or duties in the work place (common)
• DSM-5 diagnostic criteria for inattentive type.[1]
often loses things necessary for tasks or activities (e.g., toys, school
assignments, pencils, books, or tools) (common)
• DSM-5 diagnostic criteria for inattentive type.[1]
DIAGNOSIS
forget ful in daily activities (common)
• DSM-5 diagnostic criteria for inattentive type.[1]
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At tention deficit hyperactivity disorder in children Diagnosis
• DSM-5 diagnostic criteria for hyperactive-impulsive type (hyperactive symptom).[1]
processing speed impairment (i.e., the rate at which information is dealt with)
(common)
• Associated sign on neuropsychological testing.[59]
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At tention deficit hyperactivity disorder in children Diagnosis
Diagnostic tests
1st test to order
Test Result
no formal laboratory or imaging studies diagnosis is clinical
• Behaviour rating scales can be used to aid with the diagnosis.[21]
In the author's experience, a brief scale is the preferred choice, as it
reduces the burden on parents and teachers. The same scale can be
used to follow response to treatment. Commonly used scales include:
• The ADHD Rating Scale: an 18-item scale based on the DSM criteria
for ADHD. It is useful for both diagnosing ADHD in children and
adolescents and for measuring improvements with treatment.
• The Vanderbilt Scale: a 55-item scale, which assesses ADHD,
comorbid conditions, and performance. [NICHQ Vanderbilt
Assessment Scale]
• SNAP-IV is included in many research trials, including the Multimodal
Treatment Study of AD/HD (MTA). It is a 90-item scale that screens
for ADHD and other diagnoses. [SNAP-IV rating scale] [https://
mydoctor.kaiserpermanente.org/ncal/Images/Form%20ADHD
%20Snaps%20English_tcm75-150986.pdf]
• The Child Behavior Checklist (CBCL) can be used to assess a
wide range of child behavioural problems, with the CBCL-Attention
Problem (CBCL-AP) sub-scale used as a diagnostic tool for
ADHD.[61]
• Conners-Revised Scales: the most widely accepted and include a
long and short version for parents and teachers. [Conners Rating
Scales-revised (CRS-R)]
Test Result
DIAGNOSIS
neuropsychological testing normal cognitive
ability and academic
• Because ADHD is considered a behavioural disorder and is
achievement but will often
diagnosed by clinical history, neuropsychological testing is neither
have deficits in executive
necessary nor sufficient for the diagnosis.[21] However, testing
functions (those required
should be considered by a neuropsychologist in cases in which it is
to plan, prioritise, at tend
important to differentiate between ADHD and learning disabilities.
to, and inhibit behaviours)
Failing to recognise a learning disability can result in inadequate
including working
response to medication, academic failures, and low self-esteem.
memory and processing
speed
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At tention deficit hyperactivity disorder in children Diagnosis
Differential diagnosis
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At tention deficit hyperactivity disorder in children Diagnosis
DIAGNOSIS
sweating).[1]
• Careful history and mental
status examination with
collateral information will
help to distinguish from
ADHD.
• Referral to a psychiatrist
should be considered.
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At tention deficit hyperactivity disorder in children Diagnosis
Asperger's syndrome.[1]
• Careful history and mental-
status examination with
collateral information will
help to distinguish from
ADHD.
• Referral to a psychiatrist,
a neurologist, or a
developmental paediatrician
should be considered.
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At tention deficit hyperactivity disorder in children Diagnosis
DIAGNOSIS
ADHD.
• Referral to a psychiatrist
should be considered.
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At tention deficit hyperactivity disorder in children Diagnosis
opener).[66]
• Physical examination can
detect facial abnormalities.
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At tention deficit hyperactivity disorder in children Diagnosis
DIAGNOSIS
used to treat epilepsy can
impair alertness.
• History can help distinguish
from ADHD.
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At tention deficit hyperactivity disorder in children Diagnosis
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At tention deficit hyperactivity disorder in children Diagnosis
Diagnostic criteria
DSM-5 diagnostic criteria for ADHD[1]
A. Either (1) or (2):
1. Six (or more) of the following symptoms of inattention have persisted for at least 6 months to a degree
that is maladaptive and inconsistent with developmental level (older adolescents and adults require only 5 or
more):
Inattention
• Often fails to give close attention to details or makes careless mistakes in school work, work, or other
activities
• Often has difficulty sustaining attention in tasks or play activities
• Often does not seem to listen when spoken to directly
• Often does not follow through on instructions and fails to finish school work, chores, or duties in the
workplace (not due to oppositional behaviour or failure to understand instructions)
• Often has difficulty organising tasks and activities
• Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as
school work or homework)
• Often loses things necessary for tasks or activities (e.g., toys, school assignments, pencils, books, or
tools)
• Is often easily distracted by extraneous stimuli
• Is often forgetful in daily activities.
2. Six (or more) of the following symptoms of hyperactivity-impulsivity have persisted for at least 6 months to
a degree that is maladaptive and inconsistent with developmental level (older adolescents and adults require
5 or more):
Hyperactivity
DIAGNOSIS
• Often fidgets with hands or feet or squirms in seat
• Often leaves seat in classroom or in other situations in which remaining seated is expected
• Often runs about or climbs excessively in situations in which it is inappropriate (in adolescents or
adults, may be limited to subjective feelings of restlessness)
• Often has difficulty playing or engaging in leisure activities quietly
• Is often on the go or often acts as if driven by a motor
• Often talks excessively.
Impulsivity
B. Some hyperactive-impulsive or inattentive symptoms that caused impairment were present before 12
years of age.
C. Some impairment from the symptoms is present in 2 or more settings (e.g., at school [or work] and at
home).
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At tention deficit hyperactivity disorder in children Diagnosis
D. There must be clear evidence of clinically significant impairment in social, academic, or occupational
functioning.
E. The symptoms do not occur exclusively during the course of a pervasive developmental disorder,
schizophrenia, or other psychotic disorder and are not better accounted for by another mental disorder (e.g.,
mood disorder, anxiety disorder, dissociative disorder, or a personality disorder).
At least 6 of the following symptoms of attention have persisted for at least 6 months, to a degree that is
maladaptive and inconsistent with the developmental level of the child:
• Often fails to give close attention to details or makes careless errors in school work, work, or other
activities
• Often fails to sustain attention in tasks or play activities
• Often appears not to listen to what is being said to him or her
• Often fails to follow through on instructions or to finish school work, chores, or duties in the workplace
(not because of oppositional behaviour or failure to understand instructions)
• Is often impaired in organising tasks and activities
• Often avoids or strongly dislikes tasks, such as homework, that require sustained mental effort
• Often loses things necessary for certain tasks and activities, such as school assignments, pencils,
books, toys, or tools
• Is often easily distracted by external stimuli
• Is often forgetful in the course of daily activities.
Hyperactivity
At least 3 of the following symptoms of hyperactivity have persisted for at least 6 months, to a degree that is
DIAGNOSIS
At least one of the following symptoms of impulsivity has persisted for at least 6 months, to a degree that is
maladaptive and inconsistent with the developmental level of the child:
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At tention deficit hyperactivity disorder in children Diagnosis
• Onset of the disorder is no later than the age of 12 years.
Pervasiveness
The criteria should be met for more than a single situation: for example, the combination of inattention and
hyperactivity should be present both at home and at school, or at both school and another setting where
children are observed, such as a clinic. Evidence for cross-situationality will ordinarily require information
from more than one source; parental reports about classroom behaviour, for instance, are unlikely to be
sufficient.
The symptoms cause clinically significant distress or impairment in social, academic, or occupational
functioning.
The disorder does not meet the criteria for pervasive developmental disorders, manic episode, depressive
episode, or anxiety disorders.
• The ADHD Rating Scale is an 18-item scale based on the DSM criteria for ADHD. It is useful for both
diagnosing ADHD in children and adolescents and for measuring improvements with treatment.
• The Vanderbilt Scale is a 55-item scale, which assesses ADHD, comorbid conditions, and
performance. [NICHQ Vanderbilt Assessment Scale]
• SNAP-IV is included in many research trials, including the Multimodal Treatment Study
of AD/HD (MTA). It is a 90-item scale that screens for ADHD and other diagnoses.
DIAGNOSIS
[https://mydoctor.kaiserpermanente.org/ncal/Images/Form%20ADHD%20Snaps
%20English_tcm75-150986.pdf]
• The Child Behavior Checklist (CBCL) can be used to assess a wide range of child behavioural
problems, with the CBCL-Attention Problem (CBCL-AP) sub-scale used as a diagnostic tool for
ADHD.[61]
• Conners-Revised Scales are the most widely accepted and include a long and short version for
parents and teachers. [Conners Rating Scales-revised (CRS-R)]
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At tention deficit hyperactivity disorder in children Treatment
The treatment approach suggested here is derived from medical consensus statements including those of
the American Academy of Child and Adolescent Psychiatry, the American Academy of Pediatrics, and a
recent international consensus statement.[21] [70] [73] Stimulant medications are the first line of treatment,
followed by atomoxetine, and then alpha-2-adrenergic agonists, tricyclic antidepressants (TCAs), and
bupropion. Behavioural therapy can be used adjunctively. A study of physician outpatient visits demonstrated
that 87% use stimulants, 6% use atomoxetine, and 5% to 9% use alternate therapies including guanfacine,
clonidine, and bupropion.[74] A national sample of clinical practice for the period directly preceding the
issue of the American Academy of Pediatrics’ 2011 ADHD guidelines[70] demonstrated that most children
with ADHD were receiving medication treatment or behavioural therapy; just under one third received
both.[75] Multimodal treatment was most common for those with severe ADHD and those with comorbidities.
Approximately one half of preschoolers received behavioural therapy, the recommended first-line treatment
for this age group.
Psychoeducation
The patient and family should be educated about symptoms, typical course, and potential treatments.
These discussions should include coaching about educational services including 504 plans (describing
the types of accommodations that will be made for a student with ADHD in school) and individualised
education plans. Discussions can also include referral to support and advocacy organisations. [Children
and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD)] [Attention Deficit Disorder Association]
Online resources and toolkits such as parent handouts and rating scales are also available. [ADDitude
magazine] [National Initiative for Children's Healthcare Quality (NICHQ)] Psychoeducation should
also include treatment options and should consist of clear, non-technical language and evidence-based
recommendations.
Stimulant medications
Stimulant medications (drugs based on methylphenidate and amfetamine) are the first-line agents
of choice. Amfetamines and methylphenidate have been shown to be effective at improving the core
symptoms of ADHD compared with placebo, but are associated with adverse events such as sleep
problems and decreased appetite.[76] [77]
The majority of patients, between 65% to 75%, respond to an initial stimulant trial.[21] In the Multimodal
Treatment Study of AD/HD trial (MTA), the largest trial comparing stimulants with behavioural therapy in
ADHD, stimulants prescribed with regular follow-up appear to be superior to behavioural therapy after
TREATMENT
14 and 24 months.[78] [79] [80] Although the latest MTA data suggest that this advantage disappears
at 36 months, there is controversy about whether this simply reflects factors in the study design rather
than an inherent loss of stimulant efficacy with time.[78] [79] [80] Stimulants also have a larger effect
size than non-stimulant medications.[21] The long-acting preparations are recommended as they can
be given once a day (eliminating the need to repeat dosing during school hours) can last up to 12 hours
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At tention deficit hyperactivity disorder in children Treatment
or longer, depending on the delivery system,[81] and have smoother action with fewer or no rebound
symptoms at the end of the day. When titrated to an optimal dose, long-acting formulations have not
shown to be a significant cause of sleep problems in treated children.[82] Doses should be started low
(usually the smallest size marketed) and titrated weekly. Faster titration is acceptable but may result in
increased adverse effects. There is large individual variability in sensitivity to stimulants so weight is only
a rough guide of ultimate dose requirement. The dose should be titrated upwards until the elimination of
all symptoms or the appearance of unacceptable adverse effects. Often this means pushing the dose
to the maximum approved limit. Various preparations of the same medication can vary in absorption,
metabolism, and duration of action. Methylphenidate is available as a solution, an extended-release
suspension, chewable tablets, immediate-release and delayed-release tablets/capsules, and as a
transdermal patch, depending on the country. Dexmethylphenidate, the d-isomer of methylphenidate,
is also available. This variability in preparations can help individualise a regimen (e.g., by changing
to a different delivery system or supplementing a long-acting with a shorter-acting preparation). Most
studies demonstrate equivalent efficacy and side-effect profiles for methylphenidate and amfetamine
preparations, but individual patients may respond to one and not the other due to differences in their
mechanism of action as well as differences in formulation (e.g., variable delivery, absorption). One meta-
analysis of 23 clinical trials suggests that amfetamine preparations may be moderately more effective than
methylphenidate preparations; however, this result needs further confirmation in prospective head-to-head
clinical trials.[83] Therefore, the best practice in most cases is to try the other class of stimulants if the first
choice is ineffective before moving to second-line agents.
Many clinicians will consider referral to a specialist such as a child and adolescent psychiatrist after
failure of 2 stimulant trials and/or if comorbid mental disorder is suspected, or referral to a neurologist
if there is intellectual disability, seizure disorder, or a question of a genetic basis. Referral is important
if suicidal ideation appears to be a problem, although a large population-based study from Sweden
found no evidence for a positive association between the use of drug treatments for ADHD and the
risk of concomitant suicidal behaviour among patients with ADHD.[85] If anything, the results point to
a potential protective effect of drugs for ADHD on suicidal behaviour, particularly for stimulant drugs. A
population-based case series study from Hong Kong found that for patients with ADHD (aged between
6 and 25 years) prescribed methylphenidate, the risk of suicide attempts was highest in the 90 days
before treatment was started, suggesting that any link between methylphenidate use and suicidality is not
causal.[86] However, studies into the link are ongoing, and caution should be used.
Atomoxetine
Atomoxetine is a noradrenaline reuptake inhibitor and a non-stimulant medication indicated for the
treatment of ADHD. Unlike the stimulants, atomoxetine has low abuse potential and may be preferred
in patients or families with potential for misuse or abuse. Atomoxetine is generally used as a third-line
TREATMENT
treatment, but it may be an earlier option if comorbid tic disorder, anxiety disorder, or substance abuse is
present.[87]
Studies have shown atomoxetine to be more effective than placebo in reducing ADHD symptoms.[88]
[89] [90] [91] A head-to-head trial versus methylphenidate suggests that atomoxetine is non-inferior
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At tention deficit hyperactivity disorder in children Treatment
in improving ADHD symptoms.[92] 1[A]Evidence However, long-acting methylphenidate formulations
have been associated with a greater response than that observed with atomoxetine.[93] 2[A]Evidence
A retrospective chart review suggests that atomoxetine in combination with a stimulant medication may
result in better outcomes than atomoxetine alone.[94] Further studies are needed.
Dosing is once or twice daily. In contrast to stimulants that work immediately, the full effect from
atomoxetine requires several weeks of treatment. This medication does not exacerbate tics, so
can be used for patients with comorbid tics,[95] and it is also particularly useful for patients with
comorbid anxiety.[96] Regarding safety concerns, in 2005 the Food and Drug Administration in the US
recommended that a black box warning be added regarding an increase in suicidal thinking in children
and adolescents. In controlled studies, the risk was small (only 4 per 1000 cases) and there were no
completed suicides.[21] [97] This warning should be discussed with patients and family and the patient
monitored for suicidal thinking in the first few months of treatment. In addition, there have been several
cases of severe liver damage.[98] While routine monitoring of LFTs is not recommended, the medication
should be discontinued if signs of hepatic disease emerge (e.g., jaundice, dark urine). Atomoxetine can
also cause increase in heart rate and BP, and as with stimulants should be used cautiously in patients
with cardiovascular disease. As with stimulants, routine ECG screening is not recommended.
Alpha-2-adrenergic agonists
Alpha-2-adrenergic agonists are widely prescribed to treat symptoms of ADHD, as well as comorbid
aggression, stimulant-induced tics, and stimulant-induced insomnia.[99] Evidence to support their use for
symptoms of ADHD was reviewed in one meta-analysis of 11 studies, which demonstrated a moderate
effect on ADHD symptoms.[100] 3[B]Evidence Guanfacine and clonidine are both available in immediate-
release and extended-release formulations.
Guanfacine is an alpha-adrenergic agonist that is often used with ADHD patients who have comorbid
tic disorders or who cannot tolerate the stimulant medications or atomoxetine. It is less sedating than
the other alpha-adrenergic agonist, clonidine, so is often used during the daytime. The need for multiple
daily dosing makes it difficult to coordinate with school; however, the availability of an extended-release
formulation may make it more convenient (extended-release guanfacine has been shown to be useful
as monotherapy for children and adolescents with ADHD).[103] Studies have shown that treatment
with extended-release guanfacine, particularly in combination with a stimulant, is effective in reducing
the symptoms of ADHD compared with placebo.[104] [105] In addition, one double-blind study showed
effectiveness of extended-release guanfacine in patients with ADHD and oppositional symptoms.[106]
Two RCTs demonstrated that extended-release clonidine improved the symptoms of ADHD significantly
more than placebo, and that extended-release clonidine was well tolerated.[107] [108]
Expert consensus suggests alpha-2-adrenergic agonists are more effective for the hyperactive-impulsive
symptoms of ADHD than for the inattentive symptoms.[21]
As these medications are antihypertensives, occasional effects include hypotension, bradycardia, and
rebound hypertension.[100] The physician should elicit cardiovascular history before beginning treatment,
monitor BP at the initiation of the medication or during dose adjustments, and gradually adjust doses to
TREATMENT
avoid BP changes. Adverse effects include sedation, dry mouth, and dizziness.
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At tention deficit hyperactivity disorder in children Treatment
Antidepressants
If a patient fails to respond to stimulants, alpha-2-adrenergic agonists, or atomoxetine, the clinician
should review the diagnosis, consider comorbid diagnoses such as depression or learning disorders, and
consider a referral to a specialist for further treatment. Fourth-line treatments include TCAs, bupropion,
and behavioural therapy.
Bupropion has been shown in several double-blind, placebo-controlled trials to be more effective than
placebo and to have a smaller effect size than stimulant medications.[109] [110] 4[B]Evidence Because
it can lower seizure threshold, bupropion is contraindicated in patients with known seizure disorder. It is
often given in divided doses to enhance safety and minimise adverse effects.
A number of controlled trials have demonstrated the efficacy of TCAs in treatment of ADHD.[111] [112]
5[B]Evidence Clinicians should obtain an ECG before initiation of a TCA and after each dose increase
because of the risk of cardiotoxicity. The plasma level required to treat ADHD may be lower than that
required for treatment of depression, so the dose should be adjusted according to clinical symptoms to
maximum. As when using TCAs to treat depression, monitoring the plasma level may be necessary to
avoid toxicity. Frequent adverse effects include dry mouth, sedation, constipation, visual changes, and
tachycardia. Of note, TCAs can be potentially fatal in overdose, and should be avoided in patients at high
risk of suicide such as those with a past history of suicide attempts, impulsivity, and comorbid depression
or bipolar disorder.[99]
Although atypical antipsychotic prescription is common for comorbid aggression, especially in children
with autistic spectrum disorders, there are no known prospective RCTs evaluating its use in ADHD. There
is one open-label study evaluating aripiprazole but it is only pilot data and small sample size (n=14).[113]
Therefore, the use of antipsychotics as a viable treatment option in ADHD is not warranted.
Behavioural therapy consists of parent training in communication, positive feedback, effective time-
outs, and coordination of a school behavioural plan.[21] [78] The MTA study was a National Institute of
Mental Health study of 579 children with ADHD, which compared the efficacy of stimulant medications,
behavioural therapy, and combined stimulants and behavioural therapy over 14, 24, and 36 months. It
TREATMENT
determined that medications were clearly superior to behavioural treatment alone in all ADHD domains.
However, combined medication and behavioural therapy did yield improvement in key areas (including
parent and teacher ratings of inattention, parent rating of hyperactivity-impulsivity, parent rating of
oppositional/aggressive behaviours, and internalising symptoms of anxiety and depression) at a lower
dose of medication. Behavioural therapy either alone or in combination with stimulant medications is the
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At tention deficit hyperactivity disorder in children Treatment
only intervention that led to sustained improvement in parent-reported homework problems.[114] The
MTA authors concluded that combined treatment and behavioural therapy are both good treatments for
children with comorbidities or few family resources, but may not be necessary in all ADHD patients. Of
note, at 36 months, the relative benefits of behavioural therapy, combined treatment, and medication
treatment were equivocal, but this may be due to lack of rigorous follow-up in the medication arm.[80]
The Incredible Years (IY) basic parent training (PT) programme has been shown to be a valuable
intervention for preschool children with early signs of ADHD.[115]
One systematic review of treatments in adolescents found that psychosocial treatments incorporating
behaviour contingency management and motivational strategies in addition to academic, organisational,
and social skills training techniques had inconsistent effects on ADHD symptoms; however, they had clear
benefit for academic and organisational skills.[116]
Meta-analysis has shown that integrated medical and behavioural care improves outcomes compared
with usual primary care for children and adolescents with disorders including ADHD. The strongest effect
was seen with collaborative care models.[117]
Referral to specialist
A general guide is that referral to a specialist in the treatment of ADHD (e.g., child psychiatrist,
neurologist, or developmental paediatrician) should be initiated if 2 medication trials have failed or in
patients in whom comorbid psychiatric disorders are suspected (e.g., depression and ADHD) or who have
suspected epilepsy, intellectual disability, or a genetic disorder.
Ongoing ( summary )
Patient group Tx line Treatment
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At tention deficit hyperactivity disorder in children Treatment
Ongoing ( summary )
3rd atomoxetine
4th antidepressant
2nd antidepressant
TREATMENT
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At tention deficit hyperactivity disorder in children Treatment
Treatment options
Ongoing
Patient group Tx line Treatment
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
of clear, non-technical language and evidence-
based recommendations.
Primary options
» methylphenidate (immediate-release):
children 6-18 years of age: 0.3 mg/kg/dose
or 2.5 to 5 mg/dose orally once or twice daily,
increase by 0.1 mg/kg/dose or by 5-10 mg/
day increments at weekly intervals according
to response, maximum 2 mg/kg/day or 60 mg/
day
3-5 hours' duration of action when used as
primary agent, often used to supplement
longer-acting preparations.
OR
Primary options
» methylphenidate (extended-release):
children 6-18 years of age: 10-20 mg orally
once daily initially, increase if necessary
at weekly intervals according to response,
maximum 54-60 mg/day
Dose dependent on brand.
OR
Primary options
OR
Primary options
» dexmethylphenidate (immediate-release):
TREATMENT
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
OR
Primary options
» dexmethylphenidate (extended-release):
children >6 years of age: 5 mg orally
once daily initially, increase by 5 mg/day
increments at weekly intervals according to
response, maximum 30 mg/day
12 hours' duration of action.
OR
Primary options
» amfetamine/dexamfetamine (immediate-
release): children 3-5 years of age: 2.5 mg
orally once daily in the morning initially,
increase by 2.5 mg/day increments at
weekly intervals according to response
to the minimum effective dose, maximum
0.1-0.5 mg/kg/day given in 1-3 divided doses;
children at least 6 years of age: 5-10 mg/day
given in 1-2 divided doses (give first dose
on awakening, and subsequent dose 4-6
hours later) initially, increase by 5 mg/day
increments at weekly intervals according to
response, maximum 40 mg/day given in 1-3
divided doses
5-6 hours' duration of action.
OR
Primary options
» amfetamine/dexamfetamine (extended-
release): children 6-12 years of age:
5-10 mg orally once daily in the morning
initially, increase by 5 mg/day or 10 mg/day
increments at weekly intervals according
to response to the minimum effective dose,
maximum 30 mg/day; adolescents 13-17
years of age: 10 mg once daily in the morning
initially, increase by 5-10 mg/day increments
at weekly intervals to 20 mg/day, maximum
30 mg/day; adults: 20 mg once daily in the
morning initially, increase by 10 mg/day
increments at weekly intervals according
to response to the minimum effective dose,
usual dose 30 mg/day
12 hours' duration of action.
TREATMENT
OR
Primary options
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
» dexamfetamine (immediate-release):
children 3-5 years of age: 2.5 mg orally given
once daily in the morning initially, increase
by 2.5 mg/day increments at weekly intervals
according to response, maximum 40 mg/
day; children at least 6 years of age: 5 mg
once daily in the morning initially, increase
by 5 mg/day increments at weekly intervals
according to response, maximum 40 mg/day
OR
Primary options
OR
Primary options
OR
Primary options
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
child's behaviour and teaching skills to manage
it better (such as directive communication
skills, reinforcing positive behaviours, time-out
techniques, establishing a home token economy,
and anticipating non-compliant behaviours).
Primary options
» methylphenidate (immediate-release):
children 6-18 years of age: 0.3 mg/kg/dose
or 2.5 to 5 mg/dose orally once or twice daily,
increase by 0.1 mg/kg/dose or by 5-10 mg/
day increments at weekly intervals according
to response, maximum 2 mg/kg/day or 60 mg/
day
3-5 hours' duration of action when used as
primary agent, often used to supplement
longer-acting preparations.
OR
Primary options
TREATMENT
» methylphenidate (extended-release):
children 6-18 years of age: 10-20 mg orally
once daily initially, increase if necessary
at weekly intervals according to response,
maximum 54-60 mg/day
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
Dose dependent on brand.
OR
Primary options
OR
Primary options
» dexmethylphenidate (immediate-release):
children >6 years of age: 2.5 mg orally twice
daily initially, increase by 2.5 to 5 mg/day
increments at weekly intervals according to
response, maximum 20 mg/day given in 2
divided doses
6 hours' duration of action
OR
Primary options
» dexmethylphenidate (extended-release):
children >6 years of age: 5 mg orally
once daily initially, increase by 5 mg/day
increments at weekly intervals according to
response, maximum 30 mg/day
12 hours' duration of action
OR
Primary options
» amfetamine/dexamfetamine (immediate-
release): children 3-5 years of age: 2.5 mg
orally once daily in the morning initially,
increase by 2.5 mg/day increments at
weekly intervals according to response
to the minimum effective dose, maximum
0.1-0.5 mg/kg/day given in 1-3 divided doses;
children at least 6 years of age: 5-10 mg/day
TREATMENT
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
response, maximum 40 mg/day given in 1-3
divided doses
5-6 hours' duration of action
OR
Primary options
» amfetamine/dexamfetamine (extended-
release): children 6-12 years of age:
5-10 mg orally once daily in the morning
initially, increase by 5 mg/day or 10 mg/day
increments at weekly intervals according
to response to the minimum effective dose,
maximum 30 mg/day; adolescents 13-17
years of age: 10 mg once daily in the morning
initially, increase by 5-10 mg/day increments
at weekly intervals to 20 mg/day, maximum
30 mg/day; adults: 20 mg once daily in the
morning initially, increase by 10 mg/day
increments at weekly intervals according
to response to the minimum effective dose,
usual dose 30 mg/day
12 hours' duration of action
OR
Primary options
» dexamfetamine (immediate-release):
children 3-5 years of age: 2.5 mg orally given
once daily in the morning initially, increase
by 2.5 mg/day increments at weekly intervals
according to response, maximum 40 mg/
day; children at least 6 years of age: 5 mg
once daily in the morning initially, increase
by 5 mg/day increments at weekly intervals
according to response, maximum 40 mg/day
OR
Primary options
OR
Primary options
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
» lisdexamfetamine: children 6-12 years of
age: 20 mg orally once daily initially, increase
by 10 mg/day increments at weekly intervals
according to response to the minimum
effective dose, maximum 70 mg/day
Up to 14 hours' duration of action
OR
Primary options
3rd atomoxetine
» Many clinicians will consider referral to
specialist (e.g., child and adolescent psychiatrist)
after failure of 2 stimulant classes and/or
if comorbid mental disorder is suspected.
TREATMENT
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
duration of action (e.g., early morning disruptive
behaviour or late evening rebound hyperactivity).
Primary options
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
structure, establishing a point system, and daily
report cards sent home to parents for improved
coordination and reinforcement.[120] There
are no major adverse effects or complications,
although there is a potential risk of delaying
effective medication treatment if a patient has
greater than mild impairment from ADHD.
Primary options
divided doses
OR
Primary options
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
» clonidine: children ≥6 years of age: 0.1
mg orally (extended-release) once daily at
bedtime initially, increase by 0.1 mg/day
increments at weekly intervals according
to response, maximum 0.4 mg/day given
in 2 divided doses; children: 0.05 mg orally
(immediate-release) once daily initially,
increase by 0.05 mg/day increments every
3-7 days according to response, maximum
0.4 mg/day given in 3-4 divided doses
adjunct behavioural therapy
» If a patient with ADHD has a less than optimal
response to medication, has a comorbid
disorder, or experiences stressors in family life
then behavioural therapy in conjunction with
medication treatment is often beneficial.[21] [78]
4th antidepressant
» Many clinicians will consider referral to
specialist (e.g., child and adolescent psychiatrist)
after failure of 2 stimulant trials and/or if
comorbid mental disorder is suspected.
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
extended-release formulation that prevents peak
levels.
Primary options
OR
Primary options
OR
Secondary options
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
effective medication treatment if a patient has
greater than mild impairment from ADHD.
Primary options
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
day given in 1-2 divided doses, may increase
after 2-4 weeks to maximum 100 mg/day;
adolescents and children <70 kg body weight:
0.5 mg/kg/day orally once daily initially,
increase after a minimum of 4 days to 1.2 mg/
kg/day given in 1-2 divided doses, maximum
dose, the lesser of 1.4 mg/kg/day or 100 mg/
day
OR
Primary options
OR
Primary options
OR
Primary options
» methylphenidate (extended-release):
children 6-18 years of age: 10-20 mg orally
once daily initially, increase if necessary
at weekly intervals according to response,
maximum 54-60 mg/day
Dose depends on brand.
OR
TREATMENT
Primary options
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
according to response to the minimum
effective dose, maximum 70 mg/day
Up to 14 hours' duration of action
adjunct behavioural therapy
» If a patient with ADHD has a less than optimal
response to medication, has a comorbid
disorder, or experiences stressors in family life
then behavioural therapy in conjunction with
medication treatment is often beneficial.[21] [78]
2nd antidepressant
» Many clinicians will consider referral to
specialist such as a child and adolescent
psychiatrist after failure of 2 stimulant trials and/
or if comorbid mental disorder is suspected.
Referral is important if suicidal ideation appears
to be a problem, although a large population-
based study from Sweden found no evidence
for a positive association between the use
of drug treatments for ADHD and the risk of
concomitant suicidal behaviour among patients
with ADHD.[85] If anything, the results point
to a potential protective effect of drugs for
ADHD on suicidal behaviour, particularly for
stimulant drugs. A population-based case series
study from Hong Kong found that for patients
with ADHD (aged between 6 and 25 years)
prescribed methylphenidate, the risk of suicide
TREATMENT
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
» TCAs can be used for ADHD in patients
who do not tolerate stimulant medications or
atomoxetine.[123] 5[B]Evidence
Primary options
OR
Primary options
OR
Secondary options
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
» Training for classroom teachers is also
beneficial, and consists of improving classroom
structure, establishing a point system, and daily
report cards sent home to parents for improved
coordination and reinforcement.[120] There
are no major adverse effects or complications,
although there is a potential risk of delaying
effective medication treatment if a patient has
greater than mild impairment from ADHD.
based recommendations.
Primary options
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
initially, increase by 1 mg/day increments
at weekly intervals according to response,
maximum 4 mg/day; children ≥4 years of
age: 0.5 mg orally (immediate-release) once
daily at bedtime initially, increase by 0.5 mg/
day increments every 4 days according to
response, maximum 4 mg/day given in 2-4
divided doses
OR
Primary options
OR
Primary options
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At tention deficit hyperactivity disorder in children Treatment
Ongoing
Patient group Tx line Treatment
» Training for classroom teachers is also
beneficial and consists of improving classroom
structure, establishing a point system, and daily
report cards sent home to parents for improved
coordination and reinforcement.[120] There
are no major adverse effects or complications,
although there is a potential risk of delaying
effective medication treatment if a patient has
greater than mild impairment from ADHD.
TREATMENT
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At tention deficit hyperactivity disorder in children Treatment
Emerging
Modafinil
Modafinil is a stimulant medication that it is used in the US for the treatment of narcolepsy, shift-work sleep
disorder, and excessive daytime sleepiness associated with obstructive sleep apnoea. A secondary analysis
to evaluate the efficacy of modafinil in children and adolescents with ADHD using pooled data from 3 double-
blind, placebo-controlled studies has shown improvement in symptoms and behaviours in patients with the
inattentive and combined subtypes.[125] However, its use may be off-label in some countries, including the
US.
TREATMENT
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At tention deficit hyperactivity disorder in children Follow up
Recommendations
Monitoring
FOLLOW UP
Most patients with ADHD will be treated with medications. The American Academy of Child and
Adolescent Psychiatry (AACAP) practice parameters recommend that follow-up with the physician should
occur several times a year and the following parameters monitored.[21]
• Symptoms: parent and teacher rating scales can be particularly helpful in following level of
functioning at home and school. Parents and teachers should be alert for worsening of behaviours,
which may indicate need for adjustment of medication (often occurs when patient grows).
Academic failures despite treatment can be a sign of comorbid learning disorder.
• Height and weight: use of growth charts to monitor these parameters can demonstrate changes in
growth velocity. These parameters should be checked once or twice a year (or more frequently if
practical or when results are concerning). A change in height or weight that crosses 2 percentile
lines is cause for concern and a drug holiday or medication change should be considered.
• BP and pulse: baseline measures should be obtained at initiation of treatment, when dose is
adjusted, and several times annually.
• Adverse effects of medications (including anorexia, insomnia, headache, tics, and irritability):
strategies to address adverse effects include further monitoring, dose adjustment, switching
medication, or adjunctive medication to treat adverse effect. Stimulant medications have been
associated with cardiovascular side effects, although a 10-year analysis of data from the
multimodal treatment study showed no treatment effect on blood pressure.[150] These should be
monitored in children with heart conditions.[151]
• Assessment for comorbid disorders and medical conditions: careful history and mental status
examination can help elicit comorbid disorders including substance abuse.
• Periodic assessment to determine if tapering of medications is indicated. Trial off medications can
be initiated if patient has remained symptom-free for at least 1 year and should occur during a
vacation to avoid disruption of school.
Patient instructions
Complications
Monitoring of weight, giving medication with meals, and adding high-calorie snacks are recommended.
Cyproheptadine may improve appetite, but alternative delivery systems or different medication should be
considered.[131]
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At tention deficit hyperactivity disorder in children Follow up
FOLLOW UP
often be treated first with sleep hygiene techniques including elimination of caffeine, avoidance of exercise
late in the day, and strict adherence to regular sleep and wake times. Adjustment of the medication timing,
dose, and formulation (e.g., exchanging a long-acting for an intermediate-acting stimulant) may also
be tried. Finally, adjuvant medications can be helpful, including melatonin, clonidine, remeron, tricyclic
antidepressants, or trazodone.
Stimulants and atomoxetine: in 2006, the Food and Drug Administration in the US issued a black-
box warning about the cardiovascular risks of stimulant drugs.[136] However, in healthy children,
the evidence for medication-induced cardiac effects is minimal.[137] A review of the risk for sudden
death on methylphenidate, amfetamine, and atomoxetine was less than the base rate in the general
population.[138] One article demonstrated that there was no evidence that current use of an ADHD
drug was associated with an increased risk of serious cardiovascular event.[139] Another study found a
slightly increased relative risk of myocardial infarction and arrhythmias in the early period after the start
of methylphenidate treatment for ADHD in children and young people, mostly in those with a history of
congenital heart disease. This raises the importance of risk-benefit analysis, particularly in children with
mild ADHD.[140] Children with pre-existing heart disease, symptoms suggestive of heart disease (e.g.,
syncope, palpitations, chest pain, post-exercise symptoms), or a strong family history for sudden death
should be referred to a cardiologist for examination before a stimulant trial. If patients develop any cardiac
adverse effects on stimulants, they should also be referred to a cardiologist. There is no need to obtain
routine ECGs or echocardiograms on healthy patients on stimulants.
Alpha-2-adrenergic agonists: these are antihypertensives and thus have rare cardiac complications
including hypotension, bradycardia, and rebound hypertension. In addition, there has been debate in the
literature about risk of sudden death when combining clonidine with stimulants, but studies show this
combination to be safe.[141]
Tricyclic antidepressants: clinicians should obtain an ECG before initiation and after dose increases
because of the cardiotoxic potential of these medications.
Mood lability is a rare adverse effect of ADHD medications; if this occurs, clinicians may consider changing
the dose of the medications or switching to an alternative class of medications.
The Pediatric Advisory Committee of the Food and Drug Administration in the US has found very rare
reports of aggression and psychotic symptoms (specifically visual and tactile hallucinations of insects)
in post-marketing safety data. The analysis of these data is problematic, as information about dose,
comorbid diagnoses, and concomitant medication use is often unavailable. However, clinicians with
patients who develop such symptoms should likely discontinue the medication.
There is conflicting evidence regarding whether stimulants increase the rate of tics relative to placebo;
however, double-blind clinical trials have not found any increase.[142] [143] In fact, children with comorbid
tic disorders generally have a decline in tic frequency when stimulants are initiated, presumably because
there is reduction of tic-promoting stress and anxiety.[144] [145] If tics do emerge, combining or replacing
stimulant with an alpha adrenergic agonist such as clonidine or guanfacine can be helpful.[124]
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At tention deficit hyperactivity disorder in children Follow up
Parents are often concerned that stimulant treatment will cause future substance abuse; in fact, a
recent review of this topic concluded that treatment for ADHD actually decreased the risk for substance
abuse.[146] [147] Diversion and misuse of stimulants can be reduced by prescribing long-acting forms
with the least potential for diversion and misuse, and keeping close track of prescriptions.[148] Evidence
has suggested that individuals with ADHD have a significantly higher risk of cigarette smoking. However,
consistent stimulant treatment of ADHD appeared to reduce smoking risk, with a larger effect in samples
with more severe psychopathology, in one meta-analysis.[149] The majority of studies included in the
meta-analysis were naturalistic (precluding causal inferences) and most did not provide sufficient data to
examine the influence of sample demographics, treatment effectiveness, or other comorbidities.
Fairly frequent but not clinically significant except when severe enough to require reduction in dose or
change to another agent. Treatment is symptomatic.
There have been inconsistent findings regarding effects of stimulants and atomoxetine on growth, with
some studies demonstrating some small decrease in expected height gain and others demonstrating no
effect on adult height.[21] [133] The Multimodal Treatment Study of AD/HD (MTA), a 3-year follow-up of
children with ADHD combined type, showed that the group treated with stimulants had an average of 2.0
cm less height and 2.7 kg less weight than the unmedicated subgroup.[134] A proposed mechanism is
that stimulants cause blockade of the dopamine transporter, leading to increased dopamine in different
brain regions such as the hypothalamus and striatum, which mediate decreased growth. It is unclear if this
translates to a reduction in adult height or instead represents a slower tempo of growth, as proposed in
large review and cross-sectional analysis.[135] If growth delay occurs, then physicians should implement a
drug holiday during weekends, vacations, and the summer.
Prognosis
Between 60% to 85% of patients with ADHD will continue to meet criteria in adolescence, and significant
functional impairment often persists into adulthood.[126] [127] Over time, symptoms of hyperactivity tend
to remit, while impairments in attention persist. In fact, patients with the predominantly inattentive type of
ADHD often present later (e.g., middle school, high school) because their lack of hyperactivity and impulsivity
makes them less disruptive in primary school than children with combined type. Adolescents and adults
with symptoms of ADHD have higher risk for academic and professional difficulties, development of conduct
disorder and antisocial behaviours, maladaptive relationships, increased injuries and car accidents, and teen
pregnancies.[128] [129] [130]
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At tention deficit hyperactivity disorder in children Guidelines
Diagnostic guidelines
Europe
North America
GUIDELINES
Published by: American Psychiatric Association Last published: 2013
Treatment guidelines
Europe
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At tention deficit hyperactivity disorder in children Guidelines
Europe
North America
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At tention deficit hyperactivity disorder in children Online resources
Online resources
1. NICHQ Vanderbilt Assessment Scale (external link)
ONLINE RESOURCES
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At tention deficit hyperactivity disorder in children Evidence scores
Evidence scores
1. Symptom severity: there is good-quality evidence that atomoxetine is non-inferior to immediate-release
methylphenidate at improving ADHD symptoms in children and adolescents.[92]
Evidence level A: Systematic reviews (SRs) or randomized controlled trials (RCTs) of >200
participants.
2. Response to treatment: there is good-quality evidence that treatment with osmotically released
oral methylphenidate is associated with significantly greater response than that observed with
atomoxetine.[93]
Evidence level A: Systematic reviews (SRs) or randomized controlled trials (RCTs) of >200
participants.
4. Bupropion versus placebo: there is medium-quality evidence that it is well tolerated but had a smaller
effect size than stimulant medications.[109]
Evidence level B: Randomized controlled trials (RCTs) of <200 participants, methodologically
flawed RCTs of >200 participants, methodologically flawed systematic reviews (SRs) or good quality
observational (cohort) studies.
5. Tricyclic antidepressants and symptom control: there is medium-quality evidence that reports positive
effects of tricyclic antidepressants on ADHD symptoms.[111] Patients randomised to desipramine or
placebo demonstrated significant differences in behavioural improvement on desipramine.[112]
Evidence level B: Randomized controlled trials (RCTs) of <200 participants, methodologically
flawed RCTs of >200 participants, methodologically flawed systematic reviews (SRs) or good quality
observational (cohort) studies.
EVIDENCE SCORES
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At tention deficit hyperactivity disorder in children References
Key articles
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed.,
REFERENCES
(DSM-5). Washington, DC: American Psychiatric Publishing; 2013.
• World Health Organization. International classification of diseases: 10th revision, second edition.
Geneva, Switzerland: World Health Organization; 2004.
• Pliszka S, AACAP Work Group on Quality Issues. Practice parameter for the assessment and
treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child
Adolesc Psychiatry. 2007;46:894-921. Abstract
References
1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed.,
(DSM-5). Washington, DC: American Psychiatric Publishing; 2013.
2. World Health Organization. International classification of diseases: 10th revision, second edition.
Geneva, Switzerland: World Health Organization; 2004.
4. Barkley RA. Attention deficit hyperactivity disorder: a clinical handbook, 3rd ed. New York: Guilford;
2005.
5. Faraone SV, Biederman J, Jetton JG, et al. Attention deficit disorder and conduct disorder: longitudinal
evidence for a familial subtype. Psychol Med. 1997;27:291-300. Abstract
6. Biederman J, Wilens T, Mick E, et al. Is ADHD a risk factor for psychoactive substance use disorders?
Findings from a four-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry.
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7. Milberger S, Biederman J, Faraone SV, et al. ADHD is associated with early initiation of cigarette
smoking in children and adolescents. J Am Acad Child Adolesc Psychiatry. 1997;36:37-44. Abstract
8. Faraone SV, Biederman J. Do attention deficit hyperactivity disorder and major depression share
familial risk factors? J Nerv Ment Dis. 1997;185:533-541. Abstract
9. Biederman J, Faraone S, Mick E, et al. Attention-deficit hyperactivity disorder and juvenile mania: an
overlooked comorbidity? J Am Acad Child Adolesc Psychiatry. 1996;35:997-1008. Abstract
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At tention deficit hyperactivity disorder in children References
10. Spencer TJ, Biederman MD, Mick E. Attention-deficit/hyperactivity disorder: diagnosis, lifespan,
comorbidities, and neurobiology. J Pediatr Psychol. 2007;32:631-642. Abstract
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11. Pliszka SR, Carlson CL, Swanson JM. ADHD with comorbid disorders: clinical assessment and
management. New York, NY: Guilford; 1999.
12. Polanczyk G, de Lima MS, Horta BL, et al. The worldwide prevalence of ADHD: a systematic review
and metaregression analysis. Am J Psychiatry. 2007;164:942-948. Full text Abstract
13. Centers for Disease Control and Prevention. Key findings: trends in the parent-report of health care
provider-diagnosis and medication treatment for ADHD: United States, 2003-2011. February 2017.
http://www.cdc.gov/ (last accessed 7 August 2017). Full text
14. Bloom B, Cohen RA, Freeman G. Summary health statistics for U.S. children: National Health
Interview Survey, 2010. Vital Health Stat 10. 2011;250:1-80. Abstract
15. Biederman J, Faraone SV. The Massachusetts General Hospital studies of gender influences
on attention-deficit/hyperactivity disorder in youth and relatives. Psychiatr Clin North Am.
2004;27:225-232. Abstract
16. Cuffe SP, Moore CG, McKeown RE. Prevalence and correlates of ADHD symptoms in the National
Health Interview Survey. J Atten Disord. 2005;9:392-401. Abstract
17. Epstein JN, Willoughby M, Valencia EY, et al. The role of children's ethnicity in the relationship
between teacher ratings of attention-deficit/hyperactivity disorder and observed classroom behavior. J
Consult Clin Psychol. 2005;73:424-434. Abstract
18. Langley K, Holmans PA, van den Bree MB, Thapar A. Effects of low birth weight, maternal smoking in
pregnancy and social class on the phenotypic manifestation of attention deficit hyperactivity disorder
and associated antisocial behavior: investigation in a clinical sample. BMC Psychiatry. 2007;7:26. Full
text Abstract
19. Faraone SV, Perlis RH, Doyle AE, et al. Molecular genetics of attention-deficit/hyperactivity disorder.
Biol Psychiatry. 2005;57:1313-1323. Abstract
20. Waldman ID, Gizer IR. The genetics of attention deficit hyperactivity disorder. Clin Psychol Rev.
2006;26:396-432. Abstract
21. Pliszka S, AACAP Work Group on Quality Issues. Practice parameter for the assessment and
treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child
Adolesc Psychiatry. 2007;46:894-921. Abstract
22. Thapar A, O'Donovan MC, Owen MJ. The genetics of attention deficit hyperactivity disorder. Hum Mol
Genet. 2005;14:R275-R282. Full text Abstract
23. Lahat E, Heyman E, Livne A, et al. Iron deficiency in children with attention deficit hyperactivity
disorder. Isr Med Assoc J. 2011;13:530-533. Abstract
60 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 13, 2017.
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of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
At tention deficit hyperactivity disorder in children References
24. Froehlich TE, Anixt JS, Loe IM, et al. Update on environmental risk factors for attention-deficit/
hyperactivity disorder. Curr Psychiatry Rep. 2011;13:333-344. Abstract
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25. Man KK, Chan EW, Ip P, et al. Prenatal antidepressant use and risk of attention-deficit/hyperactivity
disorder in offspring: population based cohort study. BMJ. 2017;357:j2350. Full text Abstract
26. Greenhill LL. Stimulant medication treatment of children with attention deficit hyperactivity disorder. In:
Jensen PS, Cooper JR, eds. Attention deficit hyperactivity disorder: state of science. best practices.
Kingston, NH: Civic Research Institute 2002:9-1-9-27.
27. Wilens TE. Mechanism of action of agents used in attention deficit/hyperactivity disorder. J Clin
Psychiatry. 2006;67:32-38. Abstract
28. Madras BK, Miller GM, Fischman AJ. The dopamine transporter and attention-deficit/hyperactivity
disorder. Biol Psychiatry. 2005;57:1397-1409. Abstract
29. Sengupta SM, Grizenko N, Thakur GA, et al. Differential association between the norepinephrine
transporter gene and ADHD: role of sex and subtype. J Psychiatry Neurosci. 2012;37:129-137. Full
text Abstract
30. Elia J, Glessner JT, Wang K, et al. Genome-wide copy number variation study associates
metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder. Nat Genet.
2011;44:78-84. Abstract
31. Wargelius HL, Malmberg K, Larsson JO, et al. Associations of MAOA-VNTR or 5HTT-LPR alleles with
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Contributors:
// Authors:
Lawrence W. Brown, MD
Associate Professor of Neurology and Pediatrics
Director, Pediatric Neuropsychiatry Program, Children's Hospital of Philadelphia, Philadelphia, PA
DISCLOSURES: LWB declares that he has no competing interests.
// Acknowledgements:
Dr Lawrence W. Brown would like to gratefully acknowledge Dr Kristin S. Russell, Dr Howard Y. Liu, and Dr
Michael S. Jellinek, previous contributors to this monograph. KSR, HYL, and MSJ declare that they have no
competing interests.
// Peer Reviewers: