Attention Deficit Hyperactivity Disorder in Children

At tention deficit
hyperactivity
disorder in children
Straight to the point of care
Last updated: Jul 14, 2022

Table of Contents
Overview 3
Summary 3
Definition 3
Theory 4
Epidemiology 4
Aetiology 4
Pathophysiology 5
Classification 5
Case history 6
Diagnosis 8
Approach 8
History and exam 9
Risk factors 11
Investigations 13
Differentials 14
Criteria 20
Screening 24
Management 25
Approach 25
Treatment algorithm overview 31
Treatment algorithm 32
Emerging 48
Primary prevention 48
Secondary prevention 49
Patient discussions 49
Follow up 50
Monitoring 50
Complications 51
Prognosis 52
Guidelines 54
Diagnostic guidelines 54
Treatment guidelines 54
Online resources 56
References 57
Disclaimer 73
At tention deficit hyperactivity disorder in children Overview
Summary
Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset disorder characterised by
inattention, hyperactivity, and/or impulsivity demonstrated across 2 or more settings (such as home and
OVERVIEW
school).
Several inattentive or hyperactive/impulsive symptoms must be present prior to 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 particular populations.
Stimulant medications have been associated with cardiovascular side effects. These should be monitored in
children with heart conditions.
Definition
ADHD is a neuro-developmental disorder characterised by inattention, hyperactivity, and impulsivity.[1] [2] It
has a chronic course with symptoms that begin in early childhood but often persist into adult life. A key
element of the definition is that symptoms manifest in two or more settings, for example in home and school,
or home and work.[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 and anxiety disorders, such as depression and mania.[4] [5] [6] [7] [8] [9]
This topic covers the management of ADHD in children only. Please see ADHD in adults for more
information on adult care.
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jul 14, 2022.
BMJ Best Practice topics are regularly updated and the most recent version of the topics
3
can be found on bestpractice.bmj.com . Use of this content is subject to our disclaimer (.
Use of this content is subject to our) . © BMJ Publishing Group Ltd 2022. All rights reserved.
At tention deficit hyperactivity disorder in children Theory
Epidemiology
Prevalence: ADHD is one of the most common disorders of childhood. The global prevalence is around
7.2%.[1] In the US, the National Survey of Children's Health found an overall prevalence of 11% among
THEORY
children aged 4 to 17 years in 2011, while the National Health Interview Study found an estimated 8% of US
children aged 3 to 17 years had ADHD in 2010.[12] [13]
Presentations: the combined presentation accounts for 50% to 75% of all people with ADHD, the inattentive
presentation accounts for 20% to 30%, and the hyperactive-impulsive presentation accounts for 15%. Over
time, inattentive symptoms tend to persist and hyperactive-impulsive symptoms tend to diminish.[10]
Sex 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.[12] [14] This
sex 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 presentation and have lower comorbidity
with oppositional defiant disorder (ODD) and conduct disorder.[10] [14] It is therefore likely that ADHD is
under-recognised and underdiagnosed in girls.[15]
Ethnic differences: several large studies suggest that Hispanic children have a lower prevalence of ADHD
than white or black American children.[12] [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 for white
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 and income 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]
Several genetic approaches have yielded interesting data.
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]
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.
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jul 14, 2022.
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.[23] [24] Other risk factors include poverty,
THEORY
lead exposure, iron deficiency, maternal alcohol drinking during pregnancy, and psychosocial adversity.[10]
[25] [26] 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 used antidepressants
before conception or had 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.[27]
Pathophysiology
Understanding of the pathophysiology of ADHD is rapidly evolving and there is not yet a unifying theory.
Brain neurochemistry: up to 85% of ADHD patients respond to stimulants, so the mechanism of action of
methylphenidate and amfetamine provides an important clue.[28] Stimulants increase the free brain levels
of noradrenaline (norepinephrine) and dopamine by blocking presynaptic neuronal reuptake and triggering
release of these neurotransmitters, suggesting that ADHD may result from a dysfunction of noradrenaline
and dopamine.[29] One proposed theory is that abnormal dopamine transporter density contributes to the
disorder.[30] Another is that the noradrenaline transporter, and/or glutamate receptor, and/or monoamine
oxidase A transporter is involved.[31] [32] [33] ADHD brain chemistry has also been linked to dysfunctions in
the serotonergic system.[33] [34]
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.[35]
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.[36] [37]
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.[38]
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, and altered cortico-striatal-thalamic connectivity.[39] [40] Another study showed
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.[41] The neuro-imaging literature on
ADHD is growing rapidly.[42] [43] [44]
Classification
Diagnostic and Statistical Manual of Mental Disorders, 5th edition,
Text Revision (DSM-5-TR) classification of ADHD[1]
ADHD may be classified as one of the following subtypes:
5
• Combined presentation: if both inattention criterion and hyperactivity-impulsivity criterion are met for
the past 6 months.
• Predominantly inattentive presentation: if inattention criterion is met but hyperactivity-impulsivity
criterion is not met for the past 6 months.
THEORY
• Predominantly hyperactive/impulsive presentation: if hyperactivity-impulsivity criterion is met and

inattention criterion is not met for the past 6 months.
Patients may be classified as being 'in partial remission' if full criteria were previously met, fewer than the full
criteria have been met for the past 6 months, and the symptoms still result in impairment in social, academic,
or occupational functioning.
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 as the patient gets older, with hyperactive symptoms
prominent at younger ages, and inattentive symptoms more common in adolescents and adults.[10]
Atypical presentations include newly recognised symptoms in adolescents and adults. All presentations
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 and anxiety
disorders such as depression and mania.[4] [5] [6] [7] [10] [11] Of note, girls more commonly have the
inattentive presentation of ADHD and have lower comorbidity with ODD and conduct disorder.[10] Across
all presentations, there are common associated symptoms, including irritability, boredom, and difficulty
with peer interactions.
THEORY
7
At tention deficit hyperactivity disorder in children Diagnosis
Approach
The evaluation for ADHD should be comprehensive and include a thorough history from the patient and
caregivers, collateral information from school, mental status examination (MSE), and consideration of
neuropsychological testing.[21] The evaluation may be done by the primary care physician depending on
experience and comfort level. Often, busy paediatricians will refer more patients with more complex problems
to a specialist in psychiatry, neurology, or developmental behavioural paediatrics.
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, but may be underdiagnosed in females.[15] Problems that suggest ADHD 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 central nervous system trauma or infections as well as current
DIAGNOSIS
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.
Mental status examination

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 when it is important to differentiate, or identify
as a co-occurring condition, 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.
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).[60] [61] 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, and 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 for healthy patients receiving stimulants.
DIAGNOSIS
History and exam
Key diagnostic factors
presence of risk factors (common)
• Key risk factors include: family history of ADHD, low birth weight, maternal smoking during pregnancy,
and male gender.
failure to give close at tention to details or making careless mistakes in

school work, work, or other activities (common)
• DSM-5-TR diagnostic criteria for inattentive presentation.[1]
difficulty sustaining at tention in tasks or play activities (common)

does not seem to listen when spoken to directly (common)
9
does not follow through on instructions and fails to finish school work,
chores, or duties in the work place (common)
often has difficulty organising tasks and activities (common)

avoids, dislikes, or is reluctant to engage in tasks that require sustained

mental effort (such as school work or homework) (common)
often loses things necessary for tasks or activities (e.g., toys, school
assignments, pencils, books, or tools) (common)
easily distracted by extraneous stimuli (common)

forget ful in daily activities (common)

fidgets or taps with hands or feet or squirms in seat (common)

• DSM-5-TR diagnostic criteria for hyperactive-impulsive presentation (hyperactive symptom).[1]
leaves seat in classroom or in other situations in which remaining seated is

expected (common)
runs about or climbs excessively during inappropriate situations (common)

DIAGNOSIS
difficulty playing or engaging in leisure activities quietly (common)

often 'on the go' or acts as if 'driven by a motor' (common)

often talks excessively (common)

often blurts out answers before questions have been completed (common)
• DSM-5-TR diagnostic criteria for hyperactive-impulsive presentation (impulsive symptom).[1]
often has difficulty awaiting turn (common)

often interrupts or intrudes on others (e.g., but ts into conversations or
games) (common)
Other diagnostic factors

mild mood symptoms (dysphoria, mood lability, irritability, boredom)
(common)
• Associated symptom.[21]
difficulty with peer interactions (common)

• Associated symptom.[21] [62]
low self-esteem (common)

• Associated symptom, probably related to academic, peer, and personal failures.[21] Children with
ADHD are often corrected by teachers and parents multiple times throughout the day, affirming their
sense of low self-esteem.
working memory (i.e., short-term memory) impairment (common)

• Associated sign on neuropsychological testing.[60]
processing speed impairment (i.e., the rate at which information is dealt with)
(common)
• Associated sign on neuropsychological testing.[61]
Risk factors
Strong
DIAGNOSIS
family history of ADHD
• There is substantial evidence for a genetic predisposition for ADHD, with the mean heritability for
ADHD shown to be 76% based on twin studies.[19]
male sex
• 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.[12] [14] However, ADHD may be under-recognised and underdiagnosed in girls.[15]
low birth weight

• Although children with extremely low birth weight (<1000 g) form only a small percentage of all children
with ADHD, studies have found that extremely low birth weight children have 3 times the risk of
developing ADHD.[45] Low birth weight (<2500 g) is also a risk factor for ADHD.[23] [46]
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, clinical-
11
based studies commonly report ADHD in 25% to 40% of children with epilepsy.[47] While there can
be contributions from persistent seizures and/or medication, one large study of childhood absence
epilepsy found that 36% of the newly diagnosed cohort exhibited attention deficits despite otherwise
intact neurocognitive functioning.[48]
maternal nicotine use during pregnancy

• A Finnish study showed a dose-response relationship between nicotine exposure during pregnancy
(maternal cotinine levels) and prevalence of offspring ADHD.[24] A study of 356 British children with
ADHD found that maternal smoking during pregnancy increased the risk of hyperactive-impulsive
symptoms but not inattentive symptoms.[18]
tic disorders
• The co-occurence of tic disorders and dyspraxia (developmental co-ordination disorder) are increased
in children with ADHD.[1]
Weak
maternal alcohol use during pregnancy
• A study found a 2.5-fold increased risk for ADHD associated with antenatal exposure to alcohol.[46]
stress during pregnancy and labour

• Pregnancy and delivery complications such as toxaemia, eclampsia, poor maternal health,
maternal age, fetal postmaturity, duration of labour, fetal distress, low birth weight, and antepartum
haemorrhage appear to confer a predisposition for ADHD.[10] A prospective study of 290 first-time
Scandinavian mothers found gestational exposure to stress correlated with ADHD in offspring at 7
years of age.[49]
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
DIAGNOSIS
demonstrated.[50] [51] [52] These factors include severe marital discord, low social class, large family
size, paternal criminality, maternal mental disorder, and foster placement. Another study 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.[53]
traumatic brain injury

• More-severe brain injury is correlated with a greater change in ADHD symptoms.[54]
severe early deprivation

• Severe early deprivation (such as institutional rearing or child maltreatment) has been shown to
contribute to ADHD.[55]
iron deficiency
• Several studies have suggested iron deficiency may be a risk factor in the development of ADHD.[25]
[56]
Investigations
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 both for diagnosing ADHD in children and
adolescents and for measuring improvements with treatment.
• The Vanderbilt Scale: a scale that assesses ADHD, comorbid
conditions, and performance. [Vanderbilt ADHD diagnostic scales]
(https://soonersuccess.ouhsc.edu/Resources/Behavior-Rating-
Scales)
• SNAP-IV is included in many research trials, including the Multimodal
Treatment Study of AD/HD (MTA). It is a 26-item scale that screens
for hyperactive and inattentive types of ADHD and for oppositional
defiant disorder (ODD). [SNAP-IV 26 - teacher and parent rating
scale] (https://qxmd.com/calculate/calculator_147/snap-iv-26-teacher-
parent-rating-scale)
• 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.[63]
• Conners rating scales: the most widely accepted and include a long
and short version. There are three forms, to be completed by parents,
teachers, and the child, respectively.
Other tests to consider
DIAGNOSIS
Test Result
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 when it is important
to plan, prioritise, at tend
to differentiate between ADHD and learning disabilities. Failing to
to, and inhibit behaviours)
recognise a learning disability can result in inadequate response to
including working
medication, academic failures, and low self-esteem.
memory and processing
speed
13
Differentials
Condition Differentiating signs / Differentiating tests

symptoms
Learning/language • Of note, many ADHD • Neuropsychological testing:
disorder patients have comorbid pure learning-disordered
learning disorders.[21] patients will struggle with
inattention in the subject of
their disability (e.g., reading)
but perform adequately in
other academic areas. In
contrast, ADHD patients will
often demonstrate inattention
regardless of subject.
Oppositional defiant • More hostile behaviour, • Diagnosis is clinical. The

disorder anger, open defiance (at Conners rating scale and
home and school), openly the child behaviour checklist
rebellious. Most behaviours both have oppositional
are directed at an authority defiant disorder domains.
figure. The diagnosis of
oppositional defiant disorder
is not assigned if symptoms
exist along with mood or
psychotic disorder. May
often precede conduct
disorder.[64]
• Careful history and mental
status examination with
collateral information will
help to distinguish from
ADHD.
• Referral to a psychiatrist
should be considered.
DIAGNOSIS
Depression • Patients with major • No differentiating test.

depressive disorder will
report depressed mood
or loss of interest or
pleasure for at least 2
weeks in addition to 4 of
the following symptoms:
impaired sleep, feelings of
worthlessness or guilt, low
energy, poor concentration,
psychomotor slowing,
cognitive impairment,
anorexia, suicidal ideation.[1]
ADHD.

symptoms
Bipolar disorder • Bipolar disorder is • No differentiating test.
characterised by symptoms
of depression and symptoms
of mania.[1]
• Manic symptoms include
a persistently elevated,
expansive, or irritable mood
lasting at least 1 week and
3 additional symptoms
including grandiosity,
decreased sleep, very rapid
speech, disorganised and
rapidly shifting thoughts,
increased goal-directed
activities, psychomotor
agitation, and excessive
pursuit of pleasurable
activities despite negative
consequences.[1]
ADHD.
Anxiety • Symptoms of anxiety consist • No differentiating test.

of restlessness, tiring easily,
difficulty concentrating,
irritability, muscle tension,
and sleep disturbance.[1]
DIAGNOSIS
ADHD.
Psychosis • Psychotic disorders such • No differentiating test.

as schizophrenia include a
mixture of positive symptoms
(delusions, auditory or visual
hallucinations, disorganised
speech) and negative
symptoms (thought blocking
or slowed thinking, flat facial
expression) that persist for
a significant amount of time
during a 1-month period.
• Psychotic disorders are
associated with marked
social, academic, or
occupational dysfunction.[1]
15

symptoms
• Careful history and mental-
help distinguish from ADHD.
• Referral to a psychiatrist is
indicated.
Autism spectrum disorder • The most striking feature • No differentiating test.

(includes pervasive of patients with autism
developmental disorders) spectrum disorders is
impaired social interaction, a
restricted range of interests,
and difficulty adapting to
new situations. Language
development is often
significantly delayed, though
social impairment can be
the most prominent delay in
Asperger's syndrome.[1]
• Careful history and mental-
ADHD.
• Referral to a psychiatrist,
a neurologist, or a
developmental paediatrician
Intellectual disability • Defined by deficits in • Referral to a psychologist

(intellectual intellectual and adaptive for testing of intellectual and
developmental disorder) functioning that occur during adaptive functioning, and
the developmental period.[1] neuro-psychological tests.[1]
DIAGNOSIS
• Intellectual disability can be • Genetic testing may be

distinguished from ADHD performed if there is a
by its greater impairment in high degree of suspicion
areas other than inattention, based on dysmorphism
hyperactivity, or impulsivity. or organ involvement
(e.g., Down's syndrome).
Genome-wide microarray
and fragile X testing have
been recommended as
standard practice.
• Imaging, thyroid function
tests, and metabolic work-up
may help elucidate the cause
of the disorder.
Conduct disorder • Conduct disorder is a • No differentiating test.

repeated pattern of violating
the rights of others or
society's rules. These
include 4 main groups of
behaviour: aggression that
hurts people or animals,
destruction of property, lying

symptoms
or stealing, and serious rule
violations.[1]
ADHD.
Lead toxicity • Blood lead level should • Blood lead level

be obtained in high-risk
children such as those
living in poverty, recent
immigrants, and children with
developmental delay.[65]
Iron deficiency anaemia • Iron deficiency anaemia • FBC will show microcytic
can lead to pallor, fatigue, anaemia (MCV <80
irritability, and anorexia. femtolitres).
Skin findings include • Iron deficiency can be
angular stomatitis (cracking demonstrated by lower
at the corner of the transferrin saturation (serum
mouth), glossitis (tongue iron/total iron-binding
inflammation), and capacity x 100), lower serum
spooning of the fingernails. ferritin, or higher soluble
Neurocognitive deficits can transferrin receptor.[66]
also occur and may be
irreversible.
Fetal alcohol syndrome • Antenatal exposure to • No differentiating test.

alcohol can have toxic
effects on the fetal brain and
lead to impaired cognitive
DIAGNOSIS
development and higher
levels of ADHD.
• In contrast to ADHD,
however, patients with fetal
alcohol syndrome often have
a distinct facial appearance
(smooth philtrum, thin
upper lip, upturned nose,
epicanthal folds) and may
have microcephaly and
shorter stature.[67]
• Antenatal history of alcohol
exposure can be obtained by
screening mothers with the
T-ACE questions (tolerance,
annoyance, cut down, eye
opener).[68]
• Physical examination can
detect facial abnormalities.
17

symptoms
Neurocutaneous • These are a group of • Genetic testing and
syndromes heterogeneous disorders imaging based on possible
that cause tumours to syndrome.
develop primarily in the
skin and central nervous
system, although they can
affect other organs.[69]
Diagnosis is based on
physical examination as well
as neurological work-up,
which may include genetic
testing and imaging.
Hyperthyroidism • People with hyperthyroidism • Free T4 and thyroid-

also have other signs of stimulating hormone are
hypermetabolism such obtained for screening.
as sweating, significant
weight loss, palpitations,
and frequent bowel
movements.[70] History and
physical examination can
help distinguish.
Auditory or visual • In infants and toddlers, • Referral for auditory and

impairment inattentiveness may be visual testing.
secondary to hearing and
vision problems.
Child abuse or other • Psychosocial deprivation • Skeletal survey can help

environmental stressor and stress are associated demonstrate signs of
with increased risk of physical abuse.
ADHD, but not all abused
or neglected children have
DIAGNOSIS
ADHD.[51] [52] When abuse

is suspected, it is critical to
screen children separately
from their parents. A physical
examination may assist
in the diagnosis. Child-
protection services must
be notified and will gather
collateral information.
Seizure disorder • Absence seizures can lead • EEG.

to episodic impairment of
attention and focus. Drugs
used to treat epilepsy can
impair alertness.
• History can help distinguish
from ADHD.
Central nervous system • People who have had a • LP, head imaging.
infection/trauma traumatic brain injury often
have acute symptoms and

symptoms
long-term impairments that
vary by the region of injury.
• Those who have acute
central nervous system
infections will display altered
mental status and may have
delirium, headache, and
fever.
Medication adverse • Certain medications can • Serum levels of some

effects have cognitive adverse medications can be obtained
effects and this can be (e.g., carbamazepine,
recognised by reviewing theophylline, and
the medication list for phenobarbital).
suspect medication
(e.g., antihistamines,
sympathomimetics,
benzodiazepines,
theophylline, and
anticonvulsant drugs).
Substance use disorder • Intoxication or withdrawal • Urine and serum toxicology

from substances can screens.
mimic some of the
hyperactivity, impulsivity,
and inattentiveness of
ADHD. ADHD typically
has onset before 12 years
of age and is present
throughout development
and even into adulthood,
while experimentation with
substances occurs generally
DIAGNOSIS
in adolescence and adult life.
Careful history and physical
examination can distinguish
isolated substance abuse
from ADHD, although the
two are often comorbid.
Sleep disorders • Sleep disorders (e.g., • Sleep studies can give a

obstructive apnoea, periodic more definitive diagnosis.
limb movement disorder,
restless legs syndrome,
psychophysiological
insomnia, sleep-wake
cycle disorders including
inadequate sleep) affect
25% to 50% of children with
ADHD, so it is difficult to
distinguish a sleep disorder
from ADHD with sleep
problems. People with sleep
disorders can be inattentive
or hyperactive.[71]
19

symptoms
• A careful sleep history
including review of time
to sleep onset, loud
snoring, observed apnoea,
awakenings at night, and
poor sleep hygiene may
identify a sleep disorder.
Criteria
Diagnostic and Statistical Manual of Mental Disorders, 5th edition,
Text Revision (DSM-5-TR)[1]
A. A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or
development, as characterised by (1) and/or (2):
1. Inattention: 6 (or more) of the following symptoms have persisted for at least 6 months to a degree
that is inconsistent with developmental level and that negatively impacts directly on social and academic/
occupational activities. Note: the symptoms are not solely a manifestation of oppositional behaviour,
defiance, hostility, or failure to understand tasks or instructions.
• Often fails to give close attention to details or makes careless mistakes in school work, work, or during
other activities (e.g., overlooks or misses details, work is inaccurate).
• Often has difficulty sustaining attention in tasks or play activities (e.g., has difficulty remaining focused
during lectures, conversations, or lengthy reading).
• Often does not seem to listen when spoken to directly (e.g., mind seems elsewhere, even in the
absence of any obvious distraction).
• Often does not follow through on instructions and fails to finish school work, chores, or duties in the
DIAGNOSIS
workplace (e.g., starts tasks but quickly loses focus and is easily sidetracked).
• Often has difficulty organising tasks and activities (e.g., difficulty managing sequential tasks; difficulty
keeping materials and belongings in order; messy, disorganised work; has poor time management;
fails to meet deadlines).
• Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (e.g.,
school work or homework).
• Often loses things necessary for tasks or activities (e.g., school materials, pencils, books, tools,
wallets, keys, paperwork, eyeglasses, mobile telephones).
• Is often easily distracted by extraneous stimuli.
• Is often forgetful in daily activities (e.g., doing chores, running errands).
2. Hyperactivity and impulsivity: 6 (or more) of the following symptoms of have persisted for at least 6 months
to a degree that is inconsistent with developmental level and that negatively impacts directly on social
and academic/occupational activities. Note: the symptoms are not solely a manifestation of oppositional
behaviour, defiance, hostility, or failure to understand tasks or instructions.
• Often fidgets with hands or feet or squirms in seat.
• Often leaves seat in situations when remaining seated is expected (e.g., leaves his or her place in the
classroom).
• Often runs about or climbs excessively in situations in which it is inappropriate.
• Often unable to play or engage in leisure activities quietly.
• Is often 'on the go', acting as if 'driven by a motor' (e.g., is unable to be or uncomfortable being still for
extended time, as in restaurants; may be experienced by others as being restless or difficult to keep up
with).
• Often talks excessively.
• Often blurts out an answer before a question has been completed (e.g., completes people’s
sentences; cannot wait for their turn in conversation).
• Often has difficulty awaiting his or her turn (e.g., while waiting in line).
• Often interrupts or intrudes on others (e.g., butts into conversations, games, or activities; may start
using other people’s things without asking or receiving permission).
B. Some hyperactive-impulsive or inattentive symptoms that caused impairment were present before 12
years of age.
C. Several inattentive or hyperactive-impulsive symptoms are present in two or more settings (e.g., at home,
school, or work; with friends or relatives; in other activities).
D. There is clear evidence that the symptoms interfere with, or reduce the quality of, social, academic, or
occupational functioning.
E. The symptoms do not occur exclusively during the course of schizophrenia or another psychotic disorder
and are not better explained by another mental disorder (e.g., mood disorder, anxiety disorder, dissociative
disorder, personality disorder, substance intoxication or withdrawal).
Criteria from sections A, B, C, D, and E must be met for a diagnosis to be given.
Specify whether:
• Combined presentation: if both criterion A1 (inattention) and criterion A2 (hyperactivity-impulsivity) are
DIAGNOSIS
met for the past 6 months.
• Predominantly inattentive presentation: if criterion A1 (inattention) is met but criterion A2 (hyperactivity-
impulsivity) is not met for the past 6 months.
• Predominantly hyperactive/impulsive presentation: if criterion A2 (hyperactivity-impulsivity) is met and
criterion A1 (inattention) is not met for the past 6 months.
Also specify current severity:
• Mild: few, if any, symptoms in excess of those required to make the diagnosis are present, and
symptoms result in no more than minor impairments in social or occupational functioning.
• Moderate: symptoms or functional impairment between 'mild' and 'severe' are present.
• Severe: many symptoms in excess of those required to make the diagnosis, or several symptoms
that are particularly severe, are present, or the symptoms result in marked impairment in social or
occupational functioning.
Patients may be classified as being 'in partial remission' if full criteria were previously met, fewer than the full
criteria have been met for the past 6 months, and the symptoms still result in impairment in social, academic,
or occupational functioning.
21
International Classification of Diseases 11th revision (ICD-11)[2]

Hyperkinetic disorder in ICD 10th revision (ICD-10) has been replaced with ADHD in ICD-11. ADHD has also
been moved from ‘Disruptive behaviour or dissocial disorders’ to ‘Neuro-developmental disorders’ to avoid
stigma and reflect that individuals with ADHD are not intentionally disruptive.
In ICD-11, ADHD is characterised by a persistent pattern (e.g., at least 6 months) of inattention symptoms
and/or a combination of hyperactivity and impulsivity symptoms that is outside the limits of normal variation
expected for age and level of intellectual development. Symptoms vary according to chronological age and
disorder severity.
Inattention
• Several symptoms of inattention that are persistent, and sufficiently severe that they have a direct
negative impact on academic, occupational, or social functioning. Symptoms are typically from the
following clusters:
• Difficulty sustaining attention to tasks that do not provide a high level of stimulation or reward or
require sustained mental effort; lacking attention to detail; making careless mistakes in school or
work assignments; not completing tasks.
• Easily distracted by extraneous stimuli or thoughts not related to the task at hand; often does not
seem to listen when spoken to directly; frequently appears to be daydreaming or to have mind
elsewhere.
• Loses things; is forgetful in daily activities; has difficulty remembering to complete upcoming
daily tasks or activities; difficulty planning, managing and organising schoolwork, tasks and
other activities.
• Inattention may not be evident when the individual is engaged in activities that provide intense
stimulation and frequent rewards.
Hyperactivity/impulsivity
DIAGNOSIS
• Several symptoms of hyperactivity/impulsivity that are persistent, and sufficiently severe that they
have a direct negative impact on academic, occupational, or social functioning. These tend to be most
evident in structured situations that require behavioural self-control. Symptoms are typically from the
following clusters:
• Excessive motor activity; leaves seat when expected to sit still; often runs about; has difficulty
sitting still without fidgeting (younger children).
• Difficulty engaging in activities quietly; talks too much.

• Blurts out answers in school, comments at work; difficulty waiting turn in conversation, games,
or activities; interrupts or intrudes on others conversations or games.
• A tendency to act in response to immediate stimuli without deliberation or consideration of risks
and consequences (e.g., engaging in behaviours with potential for physical injury; impulsive
decisions; reckless driving).
• Evidence of significant inattention and/or hyperactivity-impulsivity symptoms prior to age 12, though
some individuals may first come to clinical attention later in adolescence.
• Manifestations of inattention and/or hyperactivity-impulsivity must be evident across multiple situations
or settings (e.g., home, school, work, with friends or relatives), but are likely to vary according to the
structure and demands of the setting.
• Symptoms are not better accounted for by another mental disorder (e.g., an anxiety or fear-related
disorder or a neuro-cognitive disorder such as delirium).
• Symptoms are not due to the effects of a substance (e.g., cocaine) or medication (e.g.,
bronchodilators, thyroid replacement medication) on the central nervous system, including withdrawal
effects, and are not due to a disease of the nervous system.
Specifiers
• The characteristics of the current clinical presentation should be described using one of the following
specifiers, which are meant to assist in recording the main reason for the current referral or services.
Predominance of symptoms refers to the presence of several symptoms of either an inattentive or
hyperactive/impulsive nature with few or no symptoms of the other type.
• Predominantly inattentive presentation: all diagnostic requirements for ADHD are met and
inattentive symptoms predominate.
• Predominantly hyperactive-impulsive presentation: all diagnostic requirements for ADHD are
met and symptoms of hyperactivity-impulsivity predominate.
• Combined presentation: all diagnostic requirements for ADHD are met and both hyperactive-
impulsive and inattentive symptoms are clinically significant aspects of the current clinical
presentation, with neither clearly predominating.
Rating scales used in diagnosis

The American Academy of Pediatrics (AAP) and the American Academy of Child and Adolescent Psychiatry
(AACAP) practice parameters suggest that clinicians incorporate one of the commonly used behaviour rating
scales in their assessment.[21] [72] Narrowband scales assess only for ADHD, whereas broadband scales
assess a variety of behaviour symptoms.[73] Neither the AAP nor the AACAP endorses a specific scale. The
same scale can be used to follow response to treatment. A list of common rating scales is available, with
DIAGNOSIS
some free online.
Commonly used scales
• The ADHD Rating Scale is an 18-item scale based on the DSM criteria for ADHD. It is useful both for
diagnosing ADHD in children and adolescents and for measuring improvements with treatment.
• The Vanderbilt Scale is a scale that assesses ADHD, comorbid conditions, and performance.
[Vanderbilt ADHD diagnostic scales] (https://soonersuccess.ouhsc.edu/Resources/Behavior-Rating-
Scales)
• SNAP-IV is included in many research trials, including the Multimodal Treatment Study of AD/
HD (MTA). It is a 26-item scale that screens for hyperactive and inattentive forms of ADHD and
for oppositional defiant disorder (ODD). [SNAP-IV 26 - teacher and parent rating scale] (https://
qxmd.com/calculate/calculator_147/snap-iv-26-teacher-parent-rating-scale)
• 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.[63]
• Conners rating scales are the most widely accepted and include a long and short version for parents,
teachers and the child.
23
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,
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 having mental health assessments.
Clinicians should be aware that:
• The presenting symptom in preschool children is often hyperactivity, while inattention is more prevalent
among adolescents with ADHD.
• ADHD is likely to be under-recognised and underdiagnosed in girls.[15]
DIAGNOSIS
At tention deficit hyperactivity disorder in children Management
Approach
ADHD often affects many areas of functioning, including school, family relationships, friendships, activities,
and self-esteem. Psychoeducation is considered a first-line intervention for all patients. Treatment should be
comprehensive as well as flexible over time as presenting symptoms and necessary supports will change as
development progresses. Treatment should be designed for the individual patient so that efficacy, tolerability,
compliance, and affordability are maximised.[74] Patients should be monitored with regular follow-up to
monitor target symptoms, outcomes, and adverse effects.[21] [75]
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
an international consensus statement.[21] [72] [76] Stimulant medications are the first line of treatment
for children older than pre-school age, 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.[77] A national sample of clinical
practice in 2009-10 demonstrated that most children with ADHD were receiving medication treatment
or behavioural therapy; just under one third received both.[78] Multimodal treatment was most common
for those with severe ADHD and those with comorbidities. Approximately one half of pre-school children
received behavioural therapy, the recommended first-line treatment for this age group.[72]
In some countries, such as the UK, pharmacological management should only be initiated and coordinated
by specialists (e.g., child and adolescent psychiatrists), although treatments may be continued and
monitored in primary care depending on locally agreed arrangements.[79] In other countries, such as the US,
pharmacological treatment may be initiated in either primary or secondary care, although specialist input is
recommended if initial treatment is ineffective.[72]
School-aged children (6-18 years): 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)] (https://chadd.org) [Attention Deficit
Disorder Association] (https://add.org) Online resources and toolkits such as parent handouts and rating
scales are available. [Vanderbilt ADHD diagnostic scales] (https://soonersuccess.ouhsc.edu/Resources/
Behavior-Rating-Scales) [ADDitude magazine] (https://www.additudemag.com) Psychoeducation should
also include treatment options and should consist of clear, non-technical language and evidence-based
recommendations.
School-aged children (6-18 years): stimulant medications

Stimulant medications (drugs based on methylphenidate and amfetamine) are the first-line agents of
choice for children above pre-school age.[80] Amfetamines and methylphenidate have been shown to
MANAGEMENT
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.[81] [82] [83] [84]
One study of adolescents and young adults (13 to 25 years old) who started taking prescription stimulants
for ADHD found that amfetamines were associated with a greater risk of new-onset psychosis than
25
methylphenidate.[85] A population-based cohort study found no evidence that methylphenidate increases
the risk of psychotic events in adolescents and young adults with ADHD, including in those with a history
of psychosis.[86]
The majority of patients, between 65% and 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 appeared to be superior to behavioural therapy after
14 and 24 months.[87] [88] [89] 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.[87] [88] [89] Stimulants also have a larger effect size than
non-stimulant medications.[21]
Long-acting stimulant preparations are recommended as they can be taken once a day (eliminating the
need to repeat dosing during school hours) can last up to 12 hours or longer, depending on the delivery
system.[90] They also have a 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.[91] 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 body 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.
Depending on the country, methylphenidate is available as a solution, an extended-release suspension,
chewable tablets, immediate-release and delayed-release tablets/capsules, and as a transdermal patch.
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.[92] 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.
School-aged children (6-18 years): alternate class of stimulant

medication
Up to 85% of patients with ADHD will respond if both stimulant classes are tried.[93] There is no
evidence-based way to predict which class of stimulants will be effective for a given patient, and multiple
trials may be necessary.
Many clinicians will consider referral to a specialist such as a child and adolescent psychiatrist (if this
has not already taken place) after failure of two stimulant trials and/or if comorbid mental disorder is
MANAGEMENT
suspected, or referral to a neurologist if there is intellectual disability, seizure disorder, or a question of a

genetic basis.
School-aged children (6-18 years): atomoxetine
Atomoxetine is a noradrenaline (norepinephrine) 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, but it may be an earlier option if comorbid tic disorder, anxiety disorder, or substance
abuse is present.[94] [95]
Studies have shown atomoxetine to be more effective than placebo in reducing ADHD symptoms.[96]
[97] [98] [99] A head-to-head trial versus methylphenidate suggests that atomoxetine is non-inferior
in improving ADHD symptoms.[100] However, long-acting methylphenidate formulations have been
associated with a greater response than that observed with atomoxetine.[101] A retrospective chart
review suggests that atomoxetine in combination with a stimulant medication may result in better
outcomes than atomoxetine alone.[102] Further studies are needed.
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, and it is also particularly useful for patients with comorbid anxiety.[95] [103] Regarding safety
concerns, atomoxetine has a black box warning concerning 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] 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.[104] While routine monitoring of liver function tests is not recommended,
the medication should be discontinued if signs of hepatic disease emerge (e.g., jaundice, dark urine).
Atomoxetine can also cause increases in heart rate and blood pressure (BP), and as with stimulants
should be used cautiously in patients with cardiovascular disease. As with stimulants, routine ECG
screening is not recommended.
School-aged children (6-18 years): alpha-2-adrenergic agonists

Alpha-2-adrenergic agonists (e.g., guanfacine, clonidine) are widely prescribed to treat symptoms of
ADHD, as well as comorbid aggression, stimulant-induced tics, and stimulant-induced insomnia.[105]
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.[106]
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.[95] 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).[107] 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.[108] [109] In addition, one double-blind study showed
effectiveness of extended-release guanfacine in patients with ADHD and oppositional symptoms.[110]
MANAGEMENT
Two randomised controlled trials (RCTs) demonstrated that extended-release clonidine improved the
symptoms of ADHD significantly more than placebo, and that extended-release clonidine was well
tolerated.[111] [112]
27
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.[106] The physician should elicit cardiovascular history before beginning treatment,
monitor BP at the initiation of the medication and during dose adjustments, and gradually adjust doses to
avoid BP changes. Adverse effects include sedation, dry mouth, and dizziness.
School-aged children (6-18 years): antidepressants

If a patient fails to respond to stimulants, atomextine, or alpha-2-adrenergic agonists, 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 (if this has not yet taken place). Fourth-line
treatments include tricyclic antidepressants (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.[113] [114] 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.[115] [116]
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.[105]
School-aged children (6-18 years): adjunctive treatments for sleep

disturbances, aggression, tics
Alpha-2-adrenergic agonists have frequently been the initial drug of choice for children with ADHD and
sleep disturbances, aggression, and tics associated with ADHD.[105]
While methylphenidate or amfetamine do not often exacerbate tics and there is no evidence that they
cause permanent tics, many families prefer to start with medication that can improve both co-existing
conditions.[95] The non-stimulants can also safely be administered in combination with stimulants.
Guanfacine and clonidine have been found to be effective in decreasing aggressive behaviour, improving
frustration tolerance, reducing conduct disorder symptoms, and in some cases lowering the dose of
stimulant medication required to treat ADHD symptoms.
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 some evidence that risperidone may reduce aggression and conduct problems in children and youths
MANAGEMENT
with disruptive behaviour disorders in the short term, but this is associated with significant weight gain,
and antipsychotic treatment may be associated with increased risk of unexpected death among children
and youths.[117] [118] Therefore, the use of antipsychotics as a viable treatment option for chlidren with
ADHD is not warranted.
School-aged children (6-18 years): adjunctive behavioural therapy
Behavioural therapy in conjunction with medication is often beneficial if a patient with ADHD has a less
than optimal response to medication, has a comorbid disorder, or experiences family stress.[21] [87]
Behavioural therapy consists of parent training in communication, positive feedback, effective time-
outs, and coordination of a school behavioural plan.[21] [87] 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
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
only intervention that led to sustained improvement in parent-reported homework problems.[119] 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.[89]
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.[120]
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.[121] There is little evidence on whether or not social skills
training for children and adolescents with ADHD is effective.[122]
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.[123]
Pre-school-aged children (4-6 years)

Parent training in behaviour management (PTBM) and/or behavioural classroom interventions are
recommended first line in this age group.[72] The aim of parent training is to help parents improve
their understanding of the child's behaviour; it also teaches 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). A formal diagnosis of ADHD is not required before
recommending parent training given that it has documented effectiveness for problematic behaviours
regardless of aetiology; instead, it is typically recommended that parents should not wait for an ADHD
diagnosis before initiating the treatment.[72] One RCT looking at pharmacological treatment for pre-
school children with an established diagnosis of ADHD found that, following parent training, around one
third of children had experienced a significant improvement in symptoms to the extent that they did not
MANAGEMENT
require medication at that time.[124]
If behavioural interventions do not provide significant improvement, and symptoms are persistent,
moderate-to-severe in severity, and consistent across home and other settings, clinicians must weigh
up the risks of starting medication before the age of 6 years versus the harm of delaying treatment;
29
specialist input from a mental health specialist with specific experience with pre-school-aged children is
recommended with respect to this decision.[72] If pharmacological treatment is required, methylphenidate
is the recommended treatment for children aged 4 and 5 years given that it has the strongest evidence
compared with other treatments for this age group, although the evidence has not yet met the threshold
required for US Food and Drug Administration (FDA) approval, and it is used on an 'off-label' basis.[72]
There is moderate evidence that methylphenidate is safe and effective in this age group, based on one
multi-site study (n=165) and a number of other smaller studies.[124] [125] Pre-school children (<6 years
of age) treated with methylphenidate generally require a lower dose and manifest more emotional adverse
effects (irritability, tearfulness) than school-aged patients. Additionally, the effect size of the stimulant
medication is smaller in pre-school children.[124]
In US practice, up to 25% of pre-school children with ADHD are treated with an alpha-2-adrenergic
agonist (such as guanfacine) despite limited evidence regarding safety and efficacy in this age
group.[126] There is preliminary evidence from one US retrospective study to suggest that use of alpha-2-
adrenergic agonists may be associated with reduced rates of irritability/moodiness compared with
stimulants (29% vs. 50%), with improvement in ADHD symptoms reported in 66% of children taking an
alpha-2-adrenergic agonist versus 78% of children taking a stimulant.[126] This offers a limited degree
of support for the preference among some specialists to consider guanfacine for pre-school children
with predominant symptoms of irritability and oppositionality, although further evidence (including RCT
evidence) is required as to the safety and efficacy of this approach, and methylphenidate remains the
first-line option in pre-school children if pharmacological treatment is required.
Referral to a specialist
A general guide is that referral to a specialist in the treatment of ADHD (e.g., a child psychiatrist,
neurologist, or developmental paediatrician) should be initiated (if this has not already taken place) if two
medication trials have failed or for patients in whom comorbid psychiatric disorders are suspected (e.g.,
depression and ADHD) or who have suspected epilepsy, intellectual disability, or a genetic disorder.
Risk of suicidal ideation

Referral is important if there is suicidal ideation. One large population-based study from Sweden found no
evidence for a positive association between the use of drug treatments for ADHD and risk of concomitant
suicidal behaviour among patients with ADHD; if anything, the results point to a potential protective
effect of drugs for ADHD on suicidal behaviour, particularly for stimulant drugs.[127] 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.[128]
However, studies into the link are ongoing, and caution should be used.
Other nonpharmacological interventions

There is no clear evidence that non-pharmacological interventions (other than behavioural therapy),
including cognitive behavioural therapy, dietary modification, meditation-based interventions (e.g.,
mindfulness and yoga), EEG feedback, and chiropractic care, are effective in the management of
MANAGEMENT
ADHD.[21] [129] [130] [131] One meta-analysis found some evidence of improvements in some clinical
symptoms and cognition in children and adolescents with ADHD given omega-3 polyunsaturated fatty
acid supplements, but data were limited.[59]
Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Ongoing ( summary )
pre-school-aged children: 4-6 years
1st parent training in behaviour management

(PTBM) and/or behavioural classroom
intervention + psychoeducation
adjunct methylphenidate or guanfacine
school-aged children: 6-18 years
no tics: no stimulant 1st stimulant (methylphenidate or

abuse potential or amfetamine) + psychoeducation
prominent anxiety
symptoms
adjunct behavioural therapy
2nd different class of stimulant

(choose amfetamine if first trial was
methylphenidate and vice versa)
3rd atomoxetine
3rd guanfacine or clonidine
4th antidepressant
no tics: with stimulant 1st non-stimulants (atomoxetine, guanfacine,

abuse potential and/ or clonidine) or stimulants with the least
or prominent anxiety potential for abuse and/or diversion +
symptoms psychoeducation
2nd antidepressant
known tic disorder or 1st guanfacine or clonidine or atomoxetine +

stimulant-induced tics psychoeducation
MANAGEMENT
31
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
MANAGEMENT
Ongoing
pre-school-aged children: 4-6 years
1st parent training in behaviour management

intervention + psychoeducation
» Parent training in behaviour management

interventions are recommended first line in this
age group.[72] The aim of parent training is
to help parents improve their understanding
of the child's behaviour; it also teaches
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).
» A formal diagnosis of ADHD is not required

before recommending parent training given that
it has documented effectiveness for problematic
behaviours regardless of aetiology; instead, it is
typically recommended that parents should not
wait for an ADHD diagnosis before initiating the
treatment.[72] One randomised controlled trial
looking at pharmacological treatment for pre-
school children with an established diagnosis
of ADHD found that, following parent training,
around one third of children had experienced
a significant improvement in symptoms to the
extent that they did not require medication at that
time.[124]
» If the child attends pre-school, behavioural

classroom interventions are also
recommended.[72]
» Psychoeducation is considered a first-line

intervention for all patients. The patient and
family should be educated about symptoms,
typical course, and potential treatments.
These discussions should include coaching
about educational services and individualised
education plans. Discussions can also
include referral to support and advocacy
organisations. [Children and Adults with
Attention-Deficit/Hyperactivity Disorder
(CHADD)] (https://chadd.org) [Attention
Deficit Disorder Association] (https://add.org)
Online resources and toolkits such as parent
handouts and rating scales are available.
MANAGEMENT
[Vanderbilt ADHD diagnostic scales] (https://

soonersuccess.ouhsc.edu/Resources/Behavior-
Rating-Scales) [ADDitude magazine] (https://
www.additudemag.com) Psychoeducation
should also include treatment options and should
33
Ongoing
consist of clear, non-technical language and
evidence-based recommendations.
adjunct methylphenidate or guanfacine
Treatment recommended for SOME patients in
selected patient group
Primary options
» methylphenidate: consult specialist for

guidance on dose
Secondary options
» guanfacine: consult specialist for guidance

on dose
» If behavioural interventions do not provide

significant improvement, and symptoms are
persistent, moderate-to-severe in severity, and
consistent across home and other settings,
clinicians must weigh up the risks of starting
medication before the age of 6 years versus
the harm of delaying treatment; specialist input
from a mental health specialist with specific
experience with pre-school-aged children is
recommended with respect to this decision.[72]
» If pharmacological treatment is required,

methylphenidate is the recommended treatment
for children aged 4 and 5 years given that it
has the strongest evidence compared with
other treatments for this age group, although
the evidence has not yet met the threshold
required for US Food and Drug Administration
(FDA) approval, and it is used on an 'off-label'
basis.[72] There is moderate evidence that
methylphenidate is safe and effective in this age
group, based on one multi-site study (n=165)
and a number of other smaller studies.[124]
[125] Pre-school children (<6 years of age)
treated with methylphenidate generally require
a lower dose and manifest more emotional
adverse effects (irritability, tearfulness) than
school-aged patients. Additionally, the effect size
of the stimulant medication is smaller in pre-
school children.[124]
» In US practice, up to 25% of pre-school

children with ADHD are treated with an alpha-2-
adrenergic agonist (such as guanfacine) despite
limited evidence regarding safety and efficacy
MANAGEMENT
in this age group.[126] There is preliminary

evidence from one US retrospective study to
suggest that use of alpha-2-adrenergic agonists
may be associated with reduced rates of
irritability/moodiness compared with stimulants
(29% vs. 50%), with improvement in ADHD
Ongoing
symptoms reported in 66% of children taking
an alpha-2-adrenergic agonist versus 78% of
children taking a stimulant.[126] This offers a
limited degree of support for the preference
among some specialists to consider guanfacine
for pre-school children with predominant
symptoms of irritability and oppositionality,
although further evidence (including randomised
controlled trial evidence) is required as to
the safety and efficacy of this approach, and
methylphenidate remains the first-line option in
pre-school children if pharmacological treatment
is required.
school-aged children: 6-18 years
no tics: no stimulant 1st stimulant (methylphenidate or

abuse potential or amfetamine) + psychoeducation
prominent anxiety
Primary options
symptoms
guidance on dose
OR
» dexmethylphenidate: consult specialist for

guidance on dose
OR
» amfetamine/dexamfetamine: consult
specialist for guidance on dose
OR
» lisdexamfetamine: consult specialist for

guidance on dose
» Stimulant medications (drugs based on

methylphenidate and amfetamine) are the
first-line agents of choice.[80] 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.[81] [82] [83]
[84]
» The choice between a methylphenidate and

an amfetamine in a stimulant-naive patient with
MANAGEMENT
ADHD is a matter of personal preference and/

or comfort with the class, as these medications
have much in common and the differences
in efficacy and adverse effects are generally
minimal, patient-specific, and difficult to predict
35
Ongoing
before a trial. 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).[21] [81] [82]
» Long-acting preparations offer greater

convenience (once-a-day dosing), privacy (do
not need to take at school), and compliance,
and are preferred in the majority of cases.
When necessary, regimens can be sculpted:
for instance, a long-acting stimulant in the
morning, followed by a short-acting stimulant
in the afternoon when the effect of the morning
dose is wearing off. The American Academy
of Child and Adolescent Psychiatry (AACAP)
practice parameters explain that physicians may
use long-acting preparations initially and there is
no need to first start with immediate-release.[21]

» There are many different brands of each

stimulant available, and dose depends on the
brand and formulation used.
» If a patient with ADHD has a less than optimal
response to medication, has a comorbid
MANAGEMENT
disorder, or experiences stressors in family

life, behavioural therapy in conjunction with
medication treatment is often beneficial.[21] [87]
» Behaviour parent training generally consists

of approximately 10 weekly group sessions,
Ongoing
and focuses on improving understanding of the
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).
» 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.[132] 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.
2nd different class of stimulant
(choose amfetamine if first trial was
methylphenidate and vice versa)
Primary options

guidance on dose
OR
» dexmethylphenidate: consult specialist for

guidance on dose
OR
» amfetamine/dexamfetamine: consult
specialist for guidance on dose
OR

guidance on dose
» Up to 85% of patients with ADHD will respond

if both stimulant classes are tried.[93] Predicting
which class of stimulants will be effective for
a given patient is not possible and multiple
trials may be necessary.[21] Many clinicians
will consider referral to a specialist (e.g., child
and adolescent psychiatrist) after failure of
two stimulant trials and/or if comorbid mental
disorder is suspected.
» Referral is important if there is suicidal

MANAGEMENT
ideation.
» There are many different brands of each

stimulant available, and dose depends on the
brand and formulation used.
37
Ongoing


3rd atomoxetine
Primary options
» atomoxetine: children <70 kg body weight:

0.5 mg/kg orally once daily in the morning for
at least 3 days, increase gradually according
to response, maximum 1.4 mg/kg/day given
in 1-2 divided doses; children >70 kg body
weight: 40 mg orally once daily in the morning
for at least 3 days, increase gradually
according to response, maximum 100 mg/day
» Many clinicians will consider referral to a

specialist (e.g., child and adolescent psychiatrist)
after failure of two stimulant classes and/or
if comorbid mental disorder is suspected.
However, it is not unreasonable to consider non-
stimulants as an alternative as monotherapy
or in combination with stimulants, especially if
there are side effects from stimulants, parental
concerns about side effects, or a need for longer
duration of action (e.g., early morning disruptive
MANAGEMENT
behaviour or late evening rebound hyperactivity).
» Atomoxetine is a non-stimulant medication

used in the treatment of ADHD. Compared with
stimulants, atomoxetine has low abuse potential,
but takes several weeks to take effect.
Ongoing
» Atomoxetine is generally used as a third-
line treatment, but it may be used first line
if comorbid tic disorder, anxiety disorder, or
substance abuse is present.[94] [95] Studies
have shown atomoxetine to be more effective
than placebo in reducing ADHD symptoms.[96]
[97] [98] [99] A head-to-head trial versus
methylphenidate suggests that atomoxetine is
non-inferior in improving ADHD symptoms.[100]
However, long-acting methylphenidate
formulations have been associated with a
greater response than that observed with
atomoxetine.[101]


3rd guanfacine or clonidine
Primary options

on dose
OR
» clonidine: consult specialist for guidance on

MANAGEMENT
dose
» Guanfacine is an alpha-2-adrenergic agonist

that is often used with ADHD patients who have
comorbid tic disorders or who cannot tolerate the
stimulant medications or atomoxetine.[95] It is
39
Ongoing
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).[107]
» 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.[106]
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 avoid
BP changes. Adverse effects include sedation,
dry mouth, and dizziness.
» Dose depends on the brand and formulation

used.


MANAGEMENT

4th antidepressant
Ongoing
Primary options
» imipramine: consult specialist for guidance

on dose
OR
» nortriptyline: consult specialist for guidance

on dose
Secondary options
» bupropion: consult specialist for guidance

on dose

specialist (e.g., child and adolescent psychiatrist)
after failure of two stimulant trials and/or if
comorbid mental disorder is suspected.
» Tricyclic antidepressants (e.g., imipramine,

nortriptyline) can be used for ADHD in patients
who do not tolerate stimulant preparations or
atomoxetine.
» Bupropion can be used for ADHD in patients

who do not tolerate stimulant preparations or
atomoxetine. Effectiveness has been shown in
one double-blind, placebo-controlled trial.[113]
It is recommended to avoid bupropion if there
is a history of seizures, although the risk can
be minimised by using the extended-release
formulation that prevents peak levels.

MANAGEMENT

41
Ongoing
no tics: with stimulant 1st non-stimulants (atomoxetine, guanfacine,
abuse potential and/ or clonidine) or stimulants with the least
or prominent anxiety potential for abuse and/or diversion +
symptoms psychoeducation
Primary options

OR

on dose
OR

dose
OR

guidance on dose
OR

guidance on dose

specialist if a comorbid mental disorder is
suspected. Patients at high risk of stimulant
abuse are those with conduct disorder and
substance use disorders.[133] Atomoxetine
and alpha-adrenergic agonists are considered
first-line treatment for these patients as they
are non-stimulant medications with low abuse
potential.[21] Patients with ADHD and anxiety
symptoms have also been shown to respond
MANAGEMENT
to treatment with these non-stimulants, with

improvement in both domains.[134] Although
lisdexamfetamine is a scheduled drug in some
countries, the abuse potential is extremely
low since the active drug is covalently bonded
to lysine and only released to its active form
Ongoing
by a slow rate-limited process. Similarly,
the technology used in some brands of
methylphenidate means that the drug is released
slowly, and there is minimal risk of abuse or
diversion.

» Dose of guanfacine, clonidine, and stimulant

medications depends on the brand and
formulation used.


MANAGEMENT

43
Ongoing
2nd antidepressant
Primary options
» imipramine: consult specialist for guidance

on dose
OR
» nortriptyline: consult specialist for guidance

on dose
Secondary options
» bupropion: consult specialist for guidance

on dose
» Many clinicians will consider referral to

a specialist (e.g., a child and adolescent
psychiatrist) after failure of two stimulant trials
and/or if comorbid mental disorder is suspected.
Referral is important if there is suicidal ideation.
One large population-based study found no
evidence for a positive association between the
use of drug treatments for ADHD and risk of
concomitant suicidal behaviour among patients
with ADHD; if anything, the results point to a
potential protective effect of drugs for ADHD
on suicidal behaviour, particularly for stimulant
drugs.[127] 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.[128] However, studies into the link
are ongoing, and caution should be used.
» Tricyclic antidepressants (e.g., imipramine,

nortriptyline) can be used for ADHD in patients
who do not tolerate stimulant medications or
atomoxetine.[135]
» Bupropion can be used for ADHD in patients

who are at high risk of substance abuse,
although it is unlikely to help in anxiety. It is
recommended to avoid bupropion if there is
a history of seizures, although the risk can
be minimised by using the extended-release
MANAGEMENT
formulation that prevents peak levels.

Ongoing


known tic disorder or 1st guanfacine or clonidine or atomoxetine +
stimulant-induced tics psychoeducation
Primary options

on dose
OR

dose
OR

» In patients with known tic disorders,

guanfacine or clonidine may be the best first-
line agent, as studies indicate they can decrease
MANAGEMENT
tic frequency and severity, as well as improving

the core symptoms of ADHD.[95] Atomoxetine is
also an option as it does not exacerbate tics.[95]
» The stimulant medications methylphenidate

and amfetamine are not contraindicated in
45
Ongoing
children with a chronic tic disorder as long as
the patient and family understand the risk of
transient worsening of tics. One randomised
controlled trial showed both safety and efficacy
of methylphenidate and clonidine, both
independently and in combination.[136]
» Patients who develop tics with stimulants

could be switched to guanfacine, clonidine, or
atomoxetine.
» Psychoeducation is considered a key

» Dose of guanfacine and clonidine depends on

the brand and formulation used.

MANAGEMENT


Ongoing
MANAGEMENT
47
Emerging
Serdexmethylphenidate/dexmethylphenidate
Serdexmethylphenidate is a prodrug of dexmethylphenidate, and dexmethylphenidate is the d-threo
enantiomer of d,l-methylphenidate, which is the more pharmacologically active enantiomer. The US Food
and Drug Administration (FDA) has approved the combination of serdexmethylphenidate (70%) and
dexmethylphenidate (30%) for the treatment of ADHD in children over the age of 6 years. After absorption
via the gastrointestinal tract, serdexmethylphenidate is converted to dexmethylphenidate and is designed
to gradually release dexmethylphenidate throughout the day. Therefore, the formulation provides rapid
symptom control with the dexmethylphenidate, and for an extended duration with the serdexmethylphenidate.
The effects have been shown to last for a period of about 12 hours in a phase 3 multi-centre randomised
controlled trial (150 children with ADHD aged 6 to 12 years).[137] There is currently no evidence that its
effects or side effects are any different than the existing extended-release formulations, some of which have
similar extended-release effects. It is not yet clear if it will be available in a form tolerable for children who
cannot swallow pills. Cost will also be a factor since many methylphenidate products now come in generic
form.
Viloxa zine
Viloxazine, an extended-release nonstimulant drug, is approved by the FDA for the treatment of ADHD in
children and young people aged 6 to 17 years. Viloxazine is a selective noradrenaline inhibitor that has
previously been used in the treatment of depression. It can be taken as capsules or sprinkled onto apple
sauce. In phase 3 studies, including in total over 1000 children and adolescents with ADHD, viloxazine
was shown to significantly improve ADHD symptoms (measured using ADHD Rating Scale-5).[138] [139]
[140] However, it may increase suicidal thoughts and actions in some children with ADHD, and monitoring is
required during the initial few months of treatment and with any dose changes.
Trigeminal nerve stimulation

In April 2019 the FDA granted marketing authorisation for the Monarch external trigeminal nerve stimulation
(eTNS) system®, the first medical device for treating ADHD. It is indicated for patients aged 7 to 12 years
who are not currently taking prescription ADHD medication. It should be used in the home during sleep under
the supervision of a carer. The device connects via a wire to a small patch on the patient's forehead. The
system delivers low-level electrical stimulation to branches of the trigeminal nerve, which sends signals to
areas of the brain thought to be involved in ADHD (i.e., those important in regulating attention, emotion, and
behaviour). In a trial, 62 children with moderate to severe ADHD used the device or a placebo device each
night for 4 weeks. The eTNS group showed significantly greater improvement in an ADHD symptom score
than the placebo group.[141]
Primary prevention
As the pathophysiology of ADHD is thought to have a strong genetic component, primary prevention
is difficult. 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.[57] [58] [59] Requiring
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.
MANAGEMENT
Secondary prevention
Secondary prevention in ADHD focuses on preventing 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, 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]
Patient discussions
Discuss the following with the patient and family members as appropriate, at diagnosis and as part of
ongoing follow-up:
• How the condition is affecting their everyday life, including education and social relationships
• Treatment options, including the various formulations, delivery systems and timing of medication
• Treatment goals - ensure that the views of the patient and family are taken into account as part of
shared decision-making in order to improve medication compliance[167]
• Sources of information and support.
Useful websites include the US Centers for Disease Control and Prevention. [CDC: attention-deficit /
hyperactivity disorder (ADHD)] (https://www.cdc.gov/ncbddd/adhd)
MANAGEMENT
49
At tention deficit hyperactivity disorder in children Follow up
Monitoring
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 the 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 the 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.[165] These should be
monitored in children with heart conditions.[166]
• 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. A 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.
Complications
Complications Timeframe Likelihood
FOLLOW UP
medication-induced anorexia short term high
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.[147]
medication-induced insomnia short term high
Meta-analysis of studies with children/adolescents who had ADHD found that stimulant medication leads
to longer sleep latency, worse sleep efficiency, and shorter sleep duration.[148] However, insomnia can
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 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.
medication-induced cardiac effects short term low
Stimulants and atomoxetine: in 2006, the US Food and Drug Administration (FDA) issued a black-
box warning about the cardiovascular risks of stimulant drugs.[152] However, in healthy children, the
evidence for medication-induced cardiac effects is minimal.[153] 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.[154] Another study found a slightly increased relative risk of myocardial infarction
and arrhythmias in the early period after starting 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.[155] 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 for healthy patients on
stimulants.
Alpha-2-adrenergic agonists: these are antihypertensives and thus have rare cardiac complications
including hypotension, bradycardia, and rebound hypertension. 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.[156]
Tricyclic antidepressants: clinicians should obtain an ECG before initiation and after dose increases
because of the cardiotoxic potential of these medications.
medication-induced mood lability short term low
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.
medication-induced psychotic symptoms short term low
The Pediatric Advisory Committee of the FDA 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
51
Complications Timeframe Likelihood

medication use is often unavailable. However, clinicians with patients who develop such symptoms should
likely discontinue the medication.
FOLLOW UP
medication-induced tics short term low
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.[157] [158] 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.[159] [160] If tics do emerge, combining or replacing
stimulant with an alpha adrenergic agonist such as clonidine or guanfacine can be helpful.[95] [136]
medication-induced substance abuse long term low
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.[161] [162] 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.[163] Evidence
has suggested that patients 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.[164] 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.
medication-induced headache variable high
Fairly frequent but not clinically significant except when severe enough to require reduction in dose or
change to another agent. Treatment is symptomatic.
medication-induced growth delay variable low
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] [149] The Multimodal Treatment Study of AD/HD (MTA), a 3-year follow-up of
children with ADHD combined presentation, 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.[150] 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 a
large review and cross-sectional analysis.[151] If growth delay occurs, physicians should implement a drug
holiday during weekends, vacations, and the summer.
Prognosis
Between 60% and 85% of patients with ADHD will continue to meet the criteria for an ADHD diagnosis
in adolescence, and significant functional impairment often persists into adulthood.[142] [143] Over time,
symptoms of hyperactivity tend to remit, while impairments in attention persist. In fact, patients with the
predominantly inattentive presentation 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 ADHD. 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.[144] [145] [146]
FOLLOW UP
53
At tention deficit hyperactivity disorder in children Guidelines
Diagnostic guidelines
United Kingdom
At tention deficit hyperactivity disorder: diagnosis and management (ht tps://

www.nice.org.uk/guidance/ng87)
Published by: National Institute for Health and Care Excellence Last published: 2019
North America
Clinical practice guideline for the diagnosis, evaluation, and treatment of

at tention-deficit/hyperactivity disorder in children and adolescents (ht tps://
www.aappublications.org/cc/adhd-evaluation-and-care-pediatric-collection)
Published by: American Academy of Pediatrics Last published: 2019
GUIDELINES
Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text

Revision (DSM-5-TR) (ht tps://ebooks.appi.org/product/diagnostic-statistical-
manual-mental-disorders-fifth-edition-text-revision-dsm5tr)
Published by: American Psychiatric Association Last published: 2022
Treatment guidelines
United Kingdom
At tention deficit hyperactivity disorder: diagnosis and management (ht tps://

www.nice.org.uk/guidance/ng87)
Published by: National Institute for Health and Care Excellence Last published: 2019
A systematic review and economic model of the effectiveness and cost-

effectiveness of methylphenidate, dexamfetamine and atomoxetine for
the treatment of at tention deficit hyperactivity disorder in children and
adolescents (ht tps://www.journalslibrary.nihr.ac.uk/hta/hta10230#/abstract)
Published by: Health Technology Assessment NHS R&D HTA Last published: 2006
Programme
At tention deficit hyperactivity disorder in children Guidelines
North America
Clinical practice guideline for the diagnosis, evaluation, and treatment of

at tention-deficit/hyperactivity disorder in children and adolescents (ht tps://
www.aappublications.org/cc/adhd-evaluation-and-care-pediatric-collection)
Published by: American Academy of Pediatrics Last published: 2019
Cardiovascular monitoring of children and adolescents with heart disease

receiving medications for at tention deficit/hyperactivity disorder (ht tps://
professional.heart.org/en/guidelines-and-statements)
Published by: American Heart Association Last published: 2008
GUIDELINES
55
At tention deficit hyperactivity disorder in children Online resources
Online resources
1. Vanderbilt ADHD diagnostic scales (https://soonersuccess.ouhsc.edu/Resources/Behavior-Rating-
Scales) (external link)
2. SNAP-IV 26 - teacher and parent rating scale (https://qxmd.com/calculate/calculator_147/snap-iv-26-

teacher-parent-rating-scale) (external link)
3. Children and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD) (https://chadd.org)

(external link)
4. Attention Deficit Disorder Association (https://add.org) (external link)
5. ADDitude magazine (https://www.additudemag.com) (external link)
6. CDC: attention-deficit / hyperactivity disorder (ADHD) (https://www.cdc.gov/ncbddd/adhd) (external

link)
ONLINE RESOURCES
At tention deficit hyperactivity disorder in children References
Key articles
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed, text
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Contributors:
// Authors:
Mark Wolraich, MD
Professor Emeritus, Pediatrics
Section of Developmental and Behavioral Pediatrics, University Oklahoma Health Sciences, Oklahoma City,
OK
DISCLOSURES: MW has chaired the American Academy of Pediatrics committee on revising the ADHD
guidelines, and is on the steering committee and a faculty member in the REACH Institute.
// Acknowledgements:
Dr Mark Wolraich would like to gratefully acknowledge Dr Lawrence W. Brown, Dr Kristin S. Russell, Dr
Howard Y. Liu, and Dr Michael S. Jellinek, previous contributors to this topic.
DISCLOSURES: LWB was reimbursed by Sunovion for participation in a Medical Advisory Board. KSR,
HYL, and MSJ declare that they have no competing interests.
// Peer Reviewers:
Brian P. Daly, PhD

Assistant Professor
College of Health Professions, Temple University, Philadelphia, PA
DISCLOSURES: BPD declares that he has no competing interests.
Mohammed Munib Haroon, MBChB

Academic Specialist Registrar
Academic Department of Paediatrics and Obstetrics and Gynaecology, Leeds University, Leeds, UK
DISCLOSURES: MMH declares that he has no competing interests.

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At tention deficit

Last updated: Jul 14, 2022

Several genetic approaches have yielded interesting data.

• Predominantly hyperactive/impulsive presentation: if hyperactivity-impulsivity criterion is met and

medications. Possible lead exposure should be considered.

Mental status examination

failure to give close at tention to details or making careless mistakes in

difficulty sustaining at tention in tasks or play activities (common)

does not seem to listen when spoken to directly (common)

often has difficulty organising tasks and activities (common)

avoids, dislikes, or is reluctant to engage in tasks that require sustained

easily distracted by extraneous stimuli (common)

forget ful in daily activities (common)

fidgets or taps with hands or feet or squirms in seat (common)

leaves seat in classroom or in other situations in which remaining seated is

runs about or climbs excessively during inappropriate situations (common)

• DSM-5-TR diagnostic criteria for hyperactive-impulsive presentation (hyperactive symptom).[1]

difficulty playing or engaging in leisure activities quietly (common)

often 'on the go' or acts as if 'driven by a motor' (common)

often talks excessively (common)

often has difficulty awaiting turn (common)

Other diagnostic factors

difficulty with peer interactions (common)

low self-esteem (common)

working memory (i.e., short-term memory) impairment (common)

low birth weight

maternal nicotine use during pregnancy

stress during pregnancy and labour

traumatic brain injury

severe early deprivation

Other tests to consider

Condition Differentiating signs / Differentiating tests

Oppositional defiant • More hostile behaviour, • Diagnosis is clinical. The

Depression • Patients with major • No differentiating test.

Condition Differentiating signs / Differentiating tests

Anxiety • Symptoms of anxiety consist • No differentiating test.

Psychosis • Psychotic disorders such • No differentiating test.

Condition Differentiating signs / Differentiating tests

Autism spectrum disorder • The most striking feature • No differentiating test.

Intellectual disability • Defined by deficits in • Referral to a psychologist

• Intellectual disability can be • Genetic testing may be

Conduct disorder • Conduct disorder is a • No differentiating test.

Condition Differentiating signs / Differentiating tests

Lead toxicity • Blood lead level should • Blood lead level

Fetal alcohol syndrome • Antenatal exposure to • No differentiating test.

Condition Differentiating signs / Differentiating tests

Hyperthyroidism • People with hyperthyroidism • Free T4 and thyroid-

Auditory or visual • In infants and toddlers, • Referral for auditory and

Child abuse or other • Psychosocial deprivation • Skeletal survey can help

ADHD.[51] [52] When abuse

Seizure disorder • Absence seizures can lead • EEG.

Condition Differentiating signs / Differentiating tests

Medication adverse • Certain medications can • Serum levels of some

Substance use disorder • Intoxication or withdrawal • Urine and serum toxicology

Sleep disorders • Sleep disorders (e.g., • Sleep studies can give a

Condition Differentiating signs / Differentiating tests

• Often fidgets with hands or feet or squirms in seat.

Criteria from sections A, B, C, D, and E must be met for a diagnosis to be given.