ATTENTION DEFICIT

HYPERACTIVITY
DISORDER
Dr.P.Manivannan
 Introduction
2

▸Most common behavioral disorder – diagnosed in OPD

▸Prevalence varies by country & region – But a Pooled estimate of

worldwide prevalence was found to be 5.29%

▸ADHD begins in childhood - < 40%  continue to meet the criteria

in teenage years.
 History
3

o 1902 George Still - wrote about children who were restless, impulsive, and inattentive, with
intense affective responses and conduct problems.

o He believed that a combination of organic and environmental factors resulted in a lack of

inhibitory control and inattention, which he thought were the primary deficits in this condition

o 1919 to 1920 After the influenza pandemic and the epidemic of encephalitis lethargica in,
children who survived the influenza pandemic frequently developed severe behavior
problems similar to those described in Still's monograph.

o The flu survivors now are thought to have suffered organic brain damage.

o For that reason, the childhood condition was termed “minimal brain damage syndrome,” even
though brain damage could not be proven.

o Not only did the term postulate an unproven etiological mechanism, it was also stigmatizing
4
History

 1937, C. Bradley published a report that d,l-amphetamine reduced restlessness and improved
concentration in children with behavior problems in a residential treatment center.

 However, this finding was ignored for 30 years until Keith Conners and Leon Isenberg evaluated the
efficacy of dextroamphetamine (d-AMP) in a double-blind, placebo-controlled trial for children with
learning disabilities and behavior problems

 early 1960s, the condition was renamed “minimal brain dysfunction.”

 this implied a specific anatomical location and possible etiology of the disorder, which was not
proven.
5
History
 ICD-9 and DSM 2 adopted term — hyperkinetic syndrome of childhood -----
reflected that hyperactivity was the core phenomenon of ADHD

 1980 version of the APA classificatory system, DSM-III, renamed this

diagnosis attention-deficit disorder (ADD)

 1987 DSM III-R, included a single criterion list requiring 8 of the 14 possible
symptoms of hyperactivity, impulsivity, and inattention be endorsed to reach
the threshold required to make the ADHD diagnosis. Duration criteria were
added, such that the behaviors needed to be present since age 7 years and
for at least 6 months.
 Definition
6

The DSM-5TM defines ADHD as

- a persistent pattern of inattention and/or hyperactivity-impulsivity

that interferes with functioning or development,
- has symptoms presenting in two or more settings
(e.g. at home, school, or work with friends or relatives; in other activities),

- negatively impacts directly on social, academic or occupational functioning.

- Onset of the symptoms should be before age 12 years

7
Diagnosis and Clinical Features

▸Most children with ADHD are referred for care because of impairment in
 academic,
 family, and/or
 peer relationship functioning.

▸Symptoms of impulsivity, overactivity, and inattention drive this

impairment across the lifespan  problems in new domains, such as
automobile driving infractions

▸Symptoms of gross motor overactivity decreases with age,

▸Presence of psychiatric comorbidity  ↑ with age, further complicating

the clinical picture.
8
Hyperactivity

▸ does not change with the set demands of the situation.

▸Therefore, children with ADHD are more active in the classroom

and less active on the playground compared to children of same
age.

▸ Activity increases occur during sleep as well.

▸The level of gross motor activity usually decreases with age, but
fidgetiness and an inner sense of restlessness may continue into
young adult life.
9
Attentional Difficulties
- most often seen in routine settings in which the youth with ADHD must sit and
carry out tasks that involve repetition under conditions of low levels of
reinforcement and external motivation.

- In these settings, the child with ADHD often show

- easy distractibility,
- inability to sustain attention on task,
- failure to follow instruction,
- inability to complete tasks without constant supervision, and
- forgetfulness in daily routines,
- not seeming to listen when spoken to,
- making careless errors on tasks in class,
- procrastinating,
- avoiding effortful mental tasks, and
- losing items necessary for schoolwork
10
11
Impulsivity
▸Impulsivity might be seen when the
child engages in dangerous activities,
yells out in class, or
interrupts or intrudes on others during games or conversations.

▸Impulsive behavior might also result in trouble with parents, teachers, or other children,
including verbal or physical fights

▸Children with ADHD might demonstrate overly quick and error-prone performance on
standardized tasks, such as the Embedded Figures Test (EFT) or the Matching Familiar
Figures Test (MFFT).

▸This tendency also shows up in school tests  Poor performance

▸because the child cannot take time to reason out the question systematically but seems
forced by internal pressures to respond quickly without thinking
12
13
14
Behavioral & Cognitive Features
▸Behavioral
▸Children with ADHD often lack persistence.

▸They become bored with interactive games with peers, and leave such games early before
they are finished.

▸They find it difficult to delay gratification.

▸Cognitive
▸difficulty with time management
▸do not develop an internal sense of pace in planning tasks.
▸This leads to problems in estimating the
actual difficulty of waiting in line,
planning how much time a task requires, or
even knowing when to come home when out playing with other children
15
Deficit of Behavioral Inhibition and Executive Functioning

Lack of behavioral inhibition /

Poor inhibitory control

ability to delay working self-regulation

motivation arousal
gratification memory of affect

▸Dysfunction in these areas is said to impair executive functioning, interfering

with goal-directed behavior.

▸This has been assessed in the laboratory using Stop Signal Tasks and the Go-No
Go test.
16
Emotional Features

▸ADHD is often associated with dysregulation of affect,

▸resulting in temper outbursts, mood lability, and reactivity.

▸Moods can change dramatically with no obvious connection with what's

going on in the environment.

▸The reaction of others and the consequences of an action are often poorly
understood by the individual with ADHD
17

Social & Emotional Features

▸Individuals have problems accurately interpreting nonverbal social cues and thus react inappropriately.

▸So peers report them to be

 intrusive, bossy, and
 insensitive to the needs of others.
trouble cooperating with other children &
 following rules in games.

Children often have

overreacting to
leading to
with ADHD strong teasing and
situations
reactions ridicule

- reliable long-
tendency to term negative
respond to verbal or predictor of
frustration in physical peer rejection
development,
social aggression
particularly in
situations
adolescence
18
Etiology
 yet to be determined

 involves functional and anatomical dysfunction in the brain's frontal cortex and basal ganglia
segments of the cortico-basal ganglia-thalamo-cortical circuits.

 These areas support the regulation of attentional resources, the programming of complex
motor behaviors, and the learning of responses to reinforcement.

 Thus symptoms of ADHD are multidimensional, suggesting the interaction of

neuroanatomical and neurochemical systems.

 The current evidence for the neurobiological factors suggests that genetics and
neurochemistry play key roles.

 Family genetic studies, including twin, sibling, adoption, and family studies, have all
suggested that genetic factors play an important role in ADHD
 “
Genetic Etiology
Twin Studies
 75 % of the variance in the transmission of ADHD genetics

 Concordance monozygotic twins (59 to 92%) > dizygotic twins (29 to 42%)
Sibling and Half-Sibling Studies
10/19 full-sib pairs were concordant for ADHD, compared with only

2/22 half-sib pairs,

 a significant difference, supporting the genetic influence on the transmission
of ADHD in families
“
Genetic Etiology
Adoption Studies
▸18%of biological relatives of adopted-away children with ADHD were found
to be at risk for the disorder versus 6 percent of the child's adopted relatives.

Family Studies
▸First-degree relatives of children with ADHD have a 20 to 25% risk for ADHD,
compared with 4 to 5% for relatives of controls.

▸If a parent has ADHD, 50 percent of his or her offspring are likely to
have that condition.
 Mode of Inheritance
 S. H. Rhee and colleagues postulated a polygenetic multiple threshold model
after analyzing sex differences in an Australian twin and sibling-pair study.

 However, differences in fit between genetic models were modest & true for
comparisons of multifactorial and single-gene inheritance.

 This suggested that symptoms of ADHD may be caused by several

interacting genes of modest effect.
 This hypothesis is consistent with ADHD's high population prevalence and high
concordance in monozygotic twins but modest recurrence risk for first-degree
relatives.
22
Genes Involved
1. Thyroid Receptor B Gene
2. Dopamine Type D2 Receptor Gene  DRD2
3. Dopamine Transporter Gene  DAT1
4. Dopamine 4 Receptor Gene  DRD4

Other Genes
1. Genes that code for dopamine β-hydroxylase  (DBH),
2. the dopamine 5 receptor (DRD5),
3. catechol-O-methyltransferase (COMT),
4. androgen receptors,
5. factors in immune function and regulation
23
Neuroanatomical Aspects
Mirsky and Castellanos described neuroanatomical correlations as a unique
multiple-component model.
Areas Neuroanatomical Correlation

superior and temporal cortices focusing of attention

external parietal and corpus striatal motor executive function

regions
Hippocampus encoding of memory traces
prefrontal cortex act of shifting from one salient
stimulus to another
brainstem areas eg - reticular sustaining of attention
thalamic nuclei
24

Hechtman's described from MRI,PET, SPECT & fMRI studies 

decreased volume and activity in prefrontal areas, anterior cingulate,
globus pallidus, caudate, thalamus, hippocampus, and cerebellum in
children with ADHD.

These findings are supported by morphological studies of Castellanos

and colleagues.
25
Neurotransmitters Involved
 Certain brain areas have been associated with specific neurotransmitters—for
example, the caudate nucleus and corpus striatum with dopamine and the median
raphe with serotonin

 Dopamine System
- The efficacy of stimulant medications in the ADHD Rx suggests that
medication may affect brain systems involving catecholamines.

 Noradrenergic System

 Serotonergic System
- weak evidence for serotonin's role in ADHD.
- TCA/MAOI  Poor Efficacy

 Nonspecific Catecholamine Hypothesis

- emerges from an imbalance among various neurotransmitters, including
norepinephrine, epinephrine, and dopamine
26
Dopamine System
targeted
code for
genes
dopamine receptors

DRD4 controls extracellular dopamine

Molecular concentrations
genetic
studies - Stimulant drugs bind strongly to DAT
- compete with dopamine molecules at the
DAT DAT site
-to prevent reuptake of dopamine back
into the presynaptic axon for metabolism.
27
Noradrenergic System
Dysfunction in brain
norepinephrine inattention,
systems, cognitive deficits,
and higher levels
a lack of inhibition of of gross motor
locus coeruleus activity
neurons

One review of plasma and urinary epinephrine concentration in children with

ADHD compared to non-ADHD children suggested an imbalance in the ratio of
epinephrine to norepinephrine, with epinephrine being much lower than normal.

Randomized clinical trials have suggested that tricyclic antidepressants (TCAs)

and atomoxetine are potent norepinephrine reuptake inhibitors (NRIs)
28
Environmental Factors
 High lead exposure and
 maternal smoking have been associated with higher rates of diagnosis of
ADHD.

 However, it has been difficult for investigators working with children affected
by adversity to determine whether their ADHD symptoms reflect a response to
- negative parenting,
- a harsh environment,
- a genetically influenced biological problem, or
- interaction among these factors.

 Researchers Summarized that further research needed for comprehensive

understanding of the possible etiology, natural history, and treatment of
ADHD.
29
Course and Prognosis

▸just when toddler learned to walk independently Parents often notice very high
levels of gross motor activity.

▸However, the energy, oppositionality, and curiosity of toddlers can be confused

with the excessive, almost random motion of older children with ADHD, so that
one must be cautious when applying the ADHD diagnosis to a preschooler.

▸Usually, the ADHD diagnosis is first applied in primary school, during grades 1 to
6, when adjustment to the sedentary learning style is compromised.

▸The motor and attentional symptoms and impairment create a consistent

picture through early adolescence, when often the external overactivity lessens
but the internal restlessness does not.
30

ADHD

60% of childhood ADHD

trouble with the law continue to be impaired
well into adult life

increased rate instability in job

substance use / of automobile status and
abuse accidents relationships
31

Treatment
32
Indications for drug treatment

▸the presence of impairment resulting from ADHD

 mild to moderate cases the first treatments are
usually behaviour therapy and education;

▸medication is indicated as the first line of therapy only in severe

cases (e.g. those diagnosed as hyperkinetic disorder), and

▸as second line when psychological approaches have not been

successful within a reasonable time (e.g. 8 weeks) or are
inappropriate.
33
Stimulant Medications

Dexmethylphenidate Dextroamphetamine Methylphenidate

Mixed salts of
amphetamine

Non stimulant Medications

Atomoxetine Tricyclic α-Adrenergic Bupropion

HCl Antidepressants Agents
34

Other Alternative Medications

SGA -
carbamazepine lithium SSRIs aripiprazole Modafinil

 have not been shown to be effective for primary symptoms of ADHD.

 might be useful in treating some comorbid conditions

 Modafinil (Provigil) failed to achieve FDA approval because of a severe

Stevens-Johnson skin rash that occurred in one patient.
35
Stimulant medication

▸psychostimulants  ability to increase central nervous system activity in brain

regions

▸Amphetamines and methylphenidates are two groups of stimulant medication

that have received U.S. Food and Drug Administration (FDA) approval for the
treatment of youth with ADHD.

▸They are marketed in both immediate release (IR) and long-acting preparations

▸All of these products include either amphetamine or methylphenidate as the

active ingredient.

▸These chemicals structurally resemble the catecholamine neurotransmitters

dopamine (DA) and norepinephrine (NE).
36
Stimulant medication
▸Psychostimulants share the ability to
- reduce gross motor overactivity,
- increase sustained attention on tasks, and
- reduce impulsive responding on laboratory measures.

▸>70% of school-age children with ADHD respond to psychostimulants;

▸some respond preferentially to methylphenidate, whereas

▸others respond preferentially to the amphetamines.

▸ 13% percent respond to placebo.

▸Greater effects occur in behavioral domains than in cognitive areas

37 Stimulant medication - Dosages
38
39
Adverse effects of Psychostimulants

▸Insomnia
▸anorexia
▸growth deceleration – which can usually be managed by symptomatic
management and/or dose reduction •

▸Dexamphetamine is an alternative CNS stimulant; effects and adverse

reactions are broadly similar to methylphenidate, but there is much less
evidence on efficacy and safety than exists for methylphenidate, and it
plays a part in illegal drug taking.

▸Both methylphenidate and dexamfetamine are Controlled Drugs;

prescriptions should be written appropriately and for not more than 28
days
40
Treatment of ADHD Comorbidities

▸Tic Disorder  Stimulants, either alone or in combination with clonidine, reduce symptoms of ADHD in
individuals with both ADHD and Tourette's syndrome

▸Seizure Disorder  Children with seizure disorders may also suffer from ADHD.
▸
▸Although MPH, lowering the seizure threshold, experiencing a first seizure when starting a psychostimulant
is extremely rare

▸Aggression and Conduct Disorder

 Children with ADHD and comorbid conduct disorder have been shown to improve
on standard doses of methylphenidate
 Stimulants also reduced negative social interactions and covert antisocial
behavior (stealing and vandalism but not cheating
41
Treatment of ADHD Comorbidities
▸Anxiety Disorder
▸ Children with ADHD and comorbid anxiety disorder are less responsive and experience more
side effects to stimulant medication than children with ADHD alone

▸careful, slow titration may have resulted in fewer side effects and better response in this
scenario

▸Analyses show that comorbid anxiety disorder does not moderate the response to
psychostimulant treatment.
▸Mood Disorder
▸children with ADHD and comorbid depression benefit less from stimulant medication than
children who have ADHD alone.

▸Generally, it is suggested that patients comorbid for ADHD and bipolar disorder be stabilized
on mood stabilizers before stimulants are introduced.
42
Treatment of ADHD Comorbidities

▸Developmental Disorders

▸ADHD-like symptoms are seen in children with mental retardation and autism
spectrum disorders (ASDs).

▸Stimulants have been shown to be beneficial in both groups, particularly in those

children with IQs greater than 50

▸For those children with combined ASD, ADHD, and severe irritability, the
psychostimulants may need to be combined with low-dose second-generation
antipsychotic medications, such as risperidone
43
NON STIMULANTS - Atomoxetine HCl - norepinephrine
reuptake inhibitor (NRI)
▸mechanism of action  selective inhibition of the presynaptic norepinephrine
transporter.

▸well absorbed after oral administration and is minimally affected by food.

▸ High-fat meals may decrease the rate of absorption.

▸Maximum plasma concentrations are reached approximately 1 to 2 hours after

ingestion.

▸98% of circulating ATX is bound to plasma protein, mainly albumin.

▸dosed by weight  no benefit from exceeding total daily doses of 1.4 mg/kg.

▸reduce ADHD behaviors in children, adolescents, and adults.

44

▸ATX is metabolized by the cytochrome P450 (CYP) 2D6 hepatic enzyme system,
resulting in a half-life of approximately 5 hours.
▸Even so, the effects of once-daily or twice-daily dosing may last for 24-hrs
▸pharmacodynamic factors play a large role in its duration of action.

▸Some Population are poor metabolizers of CYP 2D6–metabolized drugs.

▸Such individuals may experience elevated plasma concentrations—up to

fivefold—and plasma half-life might extend to 24 hours.

▸Alternatively, very slow initial titration may be required to prevent excessive

dosing of these patients.
45

 Patients taking other medications metabolized by CYP 2D6, such as fluoxetine

(Prozac), paroxetine (Paxil), and quinidine (Cardioquin), might show signs of
competitive inhibition, namely increased plasma levels of both ATX and the
competing drug.

 One large RCT conducted in Europe compared the efficacy of ATX and MPH.
Results  MPH provides a greater effect size for ADHD behaviors and is effective
in more children with ADHD than is ATX.

 It may also be suitable where stimulant diversion is a problem or when

‘dopaminergic’ adverse effects (such as tics, anxiety and stereotypies) become
problematic on stimulants.
46
Common adverse events - Atomoxetine
▸involve abdominal discomfort,
▸nausea,
▸ decrease in appetite,
▸slowdown in the rate of weight increases,
▸sedation,
▸daytime sleepiness,
▸dizziness,
▸vertigo,
▸irritability, and
▸mood swings.
▸Sexual side effects have also been reported.
▸Increased suicidality and liver toxicity, rare, but have been noted.
▸Daytime sleepiness and gastrointestinal tract problems may be
diminished by titration to full dose over 1 week in twice-daily dosing.
47
TCA
▸reductions in ADHD symptoms seen
▸Patients unresponsive to one TCA may respond to another
▸lower doses of TCAs are used in treatment of ADHD versus depression—generally 3
mg/kg per day for ADHD versus 5 mg/kg per day for depression

▸adverse events
▸Cardiovascular  most serious(death) are rarely used in children with ADHD.
▸ CV adverse events include the slowing of cardiac conduction, ↑ risk of cardiac
arrhythmias and heart block
▸ ↑ PR and QRS intervals. Such slowing
▸cholinergic side effects, such as constipation, dry mouth, or blurred vision.
▸To minimize side effects, TCAs are given to children and adolescents in divided doses.
One begins with 10 mg per day and increases up to 25 mg twice a day for adolescents.
The dose can be increased by similar amounts every 2 weeks to a maximum daily dose
of 3 mg/kg. When discontinued tapered over several weeks
48 Psychosocial Treatment of Children with ADHD

psychoeducation academic parent CBT social skills individual

organization training training therapy
skill teaching
and
remediation
Of these modalities, parent training, intensive behavior modification, and social skills training
have shown efficacy for children with ADHD in controlled trials.

Among nonpharmacological treatments, direct contingency management uses systematic

manipulation of punishments and rewards, often in specialized settings. Although it can
produce impressive effects on behavior and performance in the classroom, its effects tend not to
generalize or be maintained outside of the settings in which they are applied. In addition,
published outcomes are achieved through single-case designs.
49  Behavior therapy often is carried out in consultation with teachers and parents
regarding in-school and home management.

Intensive behavioral interventions are based on a number of principles.

These begin with psychoeducation about the course, risk factors, and long-term
outcomes of ADHD.

Second, the parents are encouraged to attend more carefully to their child's
behavior, particularly when the child complies.

 Third, the parents are trained to use time out effectively.

 Fourth,parents are instructed in establishing a contingency management or token

economy system at home.

 Then the parents learn how to manage noncompliant behaviors in public settings.
50  Finally, advances in prosocial behavior in school are supported by use of a daily report
card.

 It is crucial to evaluate the parents and family for dysfunction related to the child's ADHD.

 Parental ADHD may interfere with behavioral modification programs, indicating that
treatment of the affected parent may be necessary before the child's intervention can be
successful.

 Other dysfunctions might be present in the family as well, such as marital problems,
substance abuse, or parental depression.

 Behavior modification is successful if applied to the classroom

 In contrast, cognitive–behavioral therapy has not been shown to be effective.

 Combination of Pharmacotherapy & Behavioral treatment is effective

51 Common Behavior Rating Scales Used in Children and
Teenagers to Assess ADHD and Monitor ADHD Management
 Child Behavior Checklist (CBCL/6-18)

 A widely used measure for identifying problem behavior in youths ages 6-18
years3
 120-question checklist with items scored on a 3-point scale from 0 = not true to 2
= very true or often true3
 Scoring provides information about the presence of possible syndromes and
internalizing/externalizing problems3

 Conners-Wells' Adolescent Self-Report Scale

 A self-reporting version of the Conners' Parent and Teacher Rating Scales is
available for teenagers4
 This is a broadband scale that is used for ADHD screening rather than to aid in
diagnosis4
52

 NICHQ Vanderbilt ADHD Teacher Rating Scale (VADTRS) and Vanderbilt

ADHD Parent Rating Scale
 The teacher version assesses symptoms and performance impairment at school;

 the parent/caregiver version assesses perceptions of school performance and social

functioning6

 Items (43 for the VADTRS and 45 for the VADPRS) are rated on 4- and 5-point scales

 Higher scores indicate more severe symptoms, except for the performance section, in which
higher scores indicate greater performance in academics and classroom behavior

 ADHD Rating Scale-IV (ADHD-RS-IV)

 An 18-item scale corresponding to the 18 items in the DSM criteria that is divided into 2
subscales: hyperactivity/impulsivity and inattentiveness

 Items scored on a 4-point frequency scale ranging from 0 = never/rarely to 3 = very often9
 Available in a form for parents/caregivers and for teachers
53
References
 Comprehensive Textbook of Psychiatry – Kaplan & Saddock – 9th edition

 Synopsis of Psychiatry – Kaplan & Saddock – 11th edition

 Rutter’s Child & Adolescent Psychiatry – 4th edition

 DSM - V

 Internet
54

THANK YOU