Transcript Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity
Disorder
D. Seltzer, M.D.
1/3/2012
ADHD - Epidemiology
The MOST COMMON neurobehavioral
disorder of childhood
 One of the most extensively studied
behavioral disorder in school-age children
 One of most prevalent CHRONIC health
conditions affecting school-age children
 Background:

NOT a new disorder (1900)
 Stimulant therapy since the 1940’s

ADHD - Epidemiology
Prevalence range 1-16%
 Based on Criteria, Setting, SEC, Geographic
area
 Most epidemiologic studies suggest 5-8%
 Dx in Boys is 2.5% >Girls 9.2% ♂; 2.9% ♀

ADHD – Epidemiology / Prognosis

PERSISTS into adolescence and adulthood: 6085% of pts diagnosed in childhood.
Hyperactivity diminishes (tho adolescents/adults
may report subjective feelings of restlessness)
 Impulsivity and Inattention persist

ADHD – Epidemiology / Prognosis

Impulsivity and Inattention persist


Adolescents: often immature peer relationships
Adolescents (untreated): High Risk Behaviors



↑ auto accidents, initiate intercourse sooner, ↓ use bc,
more sexual partners, ↑ STD’s, ↑ TA pregnancies,
smoke at younger age
poor teacher relationships, impaired school functioning,
underachievement, esp reading.
Adolescents with CD ↑ risk for substance abuse


Risk for substance use d/o over lifespan 2x greater in pts w
ADHD
GIRLS: ↑anxiety, depression, ↓external locus of control.
ADHD – Epidemiology / Prognosis

Adults with ADHD
Fewer yrs of education
 Lower rates of professional employment
 Lower SEC
 ↑ work difficulties
 More job changes
 More psychological maladjustment
 More problems w legal system: arrests, traffic
tickets, MVA


Co-morbidities highly influence prognosis
ADHD

CORE SYMPTOMS
ADHD

CORE SYMPTOMS
Hyperactivity
 Impulsivity
 Inattention

ADHD - Types

Three Subtypes
Predominantly hyperactive-impulsive type
 Predominantly inattentive type
 Combined type


Predominantly Inattentive: Girls > Boys
ADHD - Associations

ASSOCIATIONS that contribute to Functional
Impairments include School failure
 poor peer relationships
 Low self-esteem and self perception
 Lower academic achievement
 Accidental injuries
 Overall adaptive function
 Family dysfunction

ADHD: Impaired Neurologic
Functions


Neurotransmitter imbalances →deficits of executive
function and motor control
Alerting/arousal system



Maintain focus
Control of attention and shifting attention
Executive function: 6 Major Tasks






shifting from one mindset or strategy to another (i.e., flexibility)
organization (e.g., anticipating both needs and problems)
planning (e.g., goal setting)
working memory (i.e., receiving, storing, then retrieving information
within short-term memory)
separating affect from cognition (i.e., detaching one's emotions from
one's reason)
inhibiting and regulating verbal and motoric action (e.g., jumping to
conclusions too quickly, difficulty waiting in line in an appropriate
fashion).
ADHD - Etiology
Heterogeneous Disorder
 Multifactorial Etiology: incorporates

Genetic
 Epigenetic
 Neural
 Cognitive
 Behavioral mechanisms (and environmental
influences)

ADHD - Etiology

Behavioral disinhibition = core deficit
Difficulties with mobilizing delayed gratification
 Ability to interrupt ongoing responses
 Interference control

ADHD - Etiology

Neurotransmitter(s) imbalance

Dominergic & Noradrenergic regulation
Thought to increase inhibitory influences
 Frontal cortical activity influencing subcortical
structures
 Impaired frontal lobe functioning +/or impairment of
subcortical connections w frontal lobes



Caudate, putamen, globus pallidus (basal ganglia)
Effects of Stimulant medication
ADHD - Etiology

Evidence from Neuroimaging Studies imply structural brain
abnormalities in ADHD pts




More widespread involvement of brain regions than originally
thought: both gray & white matter
Smaller volumes in frontal cortex, cerebellum, subcortical
structures (caudate, putamen, globus pallidus)
Smaller corpus callosum
Most consistent finding: differences in inferior cerebellar vermis


Cerebellum now being thought to contribute to cognitive fctn (pathways
with pons & thalamus), not just motor function
fMRI’s show abnormalities of brain activation in frontal-subcorticalcerebellar (fronto-striatal) circuits
Casellanos – (NIH) eg, “Developmental trajectories of brain volume abnormalities in children and adolescents w
attention-deficit/hyperactivity disorder. JAMA. 2002;288(14)1740-1748
ADHD - Etiology

Castellano et al. scanned subjects and controls
Four scans over time - ages 5 through 18
 Cerebral, cerebellar vermis, caudate, and gray &
white matter – all 4 lobes – smaller in ADHD
subjects



After corrections for total cerbral volume, only
cerebellar vermis volume remained statistically smaller.
INCIDENTAL FINDING:

Unmedicated ADHD subjects showed more white matter
loss vs medicated ADHD subjects!
ADHD - Etiology

Strong Familial Patterns



Parents & sibs of proband: 2-8x increased risk
Twin studies: >50% chance of being dx with ADHD in
second identical twin
Associations in families



ADHD and human dopamine receptor D4 gene
Norepinephrine neurons in locus ceruleus & brainstem
nuclei spread throughout brain, but esp in frontal cortex
& cingulate gyrus.
Next frontier: genomic screening

Pharmacogenetics will study effects of specific genotype on
medication response

Ex: one small study of family w 10-repeat allele of DAT1 showed
less vigorous response to MPH.
ADHD - Etiology

Biological & Psychosocial factors

Prenatal exposures




Delivery complications




Eclampsia
Fetal distress
Antepartum hemorrhage
Postnatal




Alcohol
Cocaine
Nicotine
head injuries
toxin exposure (lead)
heavy marijuana use beginning in early adolescence
Environmental



marital or family dysfunction
Parental psychopathology
low social class
ADHD – Diagnostic Criteria
DSM-IV-TR* Criteria for ADHD – Behaviors
associated w Core ADHD Symptoms
 A. Either (1) or (2)

 (1)Inattention



6 (or more) of 9 symptoms of inattention
Persisted ≥ 6 months
Interferes with function (and “to a degree that is
maladaptive and inconsistent with developmental
level”)
*Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Copyright 2000. American
Psychiatric Association.
ADHD – Diagnostic Criteria

Inattention

(a) often fails to give close attention to details or makes
careless mistakes in schoolwork, work, or other activities
(b) often has difficulty sustaining attention in tasks or play
activities
(c) often does not seem to listen when spoken to directly
(d) often does not follow through on instructions and fails to
finish school work, chores, or duties in the workplace (not due
to oppositional behavior or failure to understand instructions)
(e) often has difficulty organizing tasks and activities
(f) often avoids, dislikes, or is reluctant to engage in tasks that
require sustained mental effort (e.g., schoolwork or homework)
(g) often loses things necessary for tasks or activities (e.g., toys,
school assignments, pencils, books, or tools)
(h) is often easily distracted by extraneous stimuli
(i) is often forgetful in daily activities
ADHD – Diagnostic Criteria

(2) Hyperactivity – Impulsivity
6 (or more) of 9 symptoms of HI
 Persisted ≥ 6 months
 Interferes with function (and “to a degree that
is maladaptive and inconsistent with
developmental level”)

ADHD – Diagnostic Criteria

Hyperactivity
(a) often fidgets with hands or feet or squirms in seat
(b) often leaves seat in classroom or in other situations in which
remaining seated is expected
(c) often runs about or climbs excessively in situations in which it is
inappropriate (in adolescents or adults, may be limited to subjective
feelings of restlessness)
(d) often has difficulty playing or engaging in leisure activities quietly
(e) is often "on the go" or often acts as if "driven by a motor"
(f) often talks excessively

Impulsivity
(g) often blurts out answers before questions have been completed
(h) often has difficulty awaiting turn
(i) often interrupts or intrudes on others (e.g., butts into conversations
or games)
ADHD – Diagnostic Criteria

Additional Criteria:




B. Some hyperactive-impulsive or inattentive symptoms that
caused impairment were present before age 7 years.
C. Some impairment from the symptoms is present in two or
more settings (e.g., at school [or work] and at home).
D. There must be clear evidence of clinically significant
impairment in social, academic, or occupational functioning.
E. The symptoms do not occur exclusively during the course
of a pervasive developmental disorder, schizophrenia, or other
psychotic disorder and are not better accounted for by
another mental disorder (eg, mood disorder, anxiety
disorders, dissociative disorders, or a personality disorder).
ADHD – Diagnostic Criteria for
Subtypes


Core Symptoms of ADHD (Adapted From the DSM-IV-TR)
INATTENTION DIMENSION
HYPERACTIVITY – IMPULSIVITY DIMENSION
INATTENTION
HYPERACTIVITY
IMPULSIVITY
Careless mistakes
Fidgety
Blurts answers bef questions are
completed
Difficulty sustaining attention
Unable to stay seated
Difficulty awaiting turn
Seems not to listen
Moves excessively (restless)
Interrupts/intrudes on others
Fails to finish tasks
Difficulty engaging in leisure
activities quietly
Talks excessively
Difficulty organizing
“On the go”
ADHD – Diagnostic Criteria for
Subtypes

DSM-IV-TR2 criteria define 3 subtypes of ADHD:

● ADHD primarily of the inattentive type 314.00(ADHD/I,
having the inappropriately often occurrence of at least 6 of 9
inattention behaviors and less than 6 hyperactive-impulsive
behaviors);

● ADHD primarily of the hyperactive-impulsive type
314.01(ADHD/HI, having the inappropriately often occurrence
of at least 6 of 9 hyperactive-impulsive behaviors and less than
6 inattention behaviors);

● ADHD combined type 314.01 (ADHD/C, having the
inappropriately often occurrence of at least 6 of 9 behaviors in
both the inattention and hyperactive-impulsive dimensions).
ADHD – Evidence based practice

American Academy of Pediatrics published an
evidenced based practice guideline for the
diagnosis of school-age children with ADHD:
American Academy of Pediatrics Subcommitee on
Attention-Deficit/hyperactivity Disorder, steering
Committee on Quality Improvement and
Management. ADHD: Clinical Practice Guideline for
the Diagnosis, Evaluation, and Treatment of AttentionDeficit/Hyperactivity Disorder in Children and
Adolescents. Pediatrics. 2011;128:1158-1022
ADHD – Evidence based practice

1. Evaluate for ADHD for children
4 through 18 years of age
 presents with academic or behavioral problems and
symptoms of inattention, hyperactivity, or impulsivity


2. To make a diagnosis of ADHD, determine that
DSM-IV criteria have been met (including
documentation of impairment in more than one
major setting)


Information should be obtained primarily from parents or guardians,
teachers, and other school and mental health clinicians involved in
the child’s care.
also rule out any alternative cause (see DDX below)
ADHD – Evidence based practice

3. During evaluation for ADHD, should include
assessment for other conditions that may
coexist with ADHD

emotional or behavioral


developmental


eg, anxiety, depressive, oppositional defiant, and conduct
disorders,
eg, learning and language disorders or other
neurodevelopmental disorders,
physical

eg, tics, sleep apnea
ADHD – Evidence based practice

4. Recognize ADHD as a chronic condition


consider children and adolescents with ADHD as
children and youth with special health care needs.
Management of children and youth with
special health care needs should follow the
principles of the chronic care model and the
medical home.
ADHD – Evidence based practice

5. Recommendations for treatment of children and
youth with ADHD vary depending on the patient’s
age:

a. For preschool-aged children (4–5 years of age), should


Prescribe evidence-based parent- and/or teacher-administered
behavior therapy as the first line of treatment
may prescribe methylphenidate



if the behavior interventions do not provide significant
improvement
there is moderate-to severe continuing disturbance in the child’s
function.
In areas where evidence-based behavioral treatments are not
available, clinician needs to weigh the risks of starting
medication at an early age against the harm of delaying
diagnosis and treatment (quality of evidence
ADHD – Evidence based practice

b. For elementary school–aged children (6–11 years
of age),
prescribe US Food and Drug Administration–approved
medications for ADHD and/or evidence-based
parentand/
 or teacher-administered behavior therapy as treatment
for ADHD, preferably both
 The evidence is particularly strong for stimulant
medications and sufficient but less strong for
atomoxetine, extended-release guanfacine, and
extended-release clonidine (in that order)
 The school environment, program, or placement is a
part of any treatment plan.

ADHD – Evidence based practice

c. For adolescents (12–18 years of age),
prescribe Food and Drug Administration–approved
medications for ADHD with the assent of the
adolescent
 may prescribe behavior therapy as treatment for ADHD
 preferably both.


6. The clinician should titrate doses of
medication for ADHD to achieve maximum
benefit with minimum adverse effects
ADHD – Evidence based practice
Many of the treatment guidelines based on MTA
(Multimodal Therapy of ADHD) studies:
 A 14-month randomized clinical trial of treatment
strategies for attention-deficit/hyperactivity disorder.
The MTA Cooperative Group. Multimodal Treatment
Study of Children With ADHD. Arch Gen Psychiatry.
1999;56(12):1073–1086

Jensen P, Hinshaw SP, Swanson JM, et al. Findings from
the NIMH multimodal treatment study of ADHD
(MTA): implications and applications for primary care
providers. J Dev Behav Pediatr. 2001;22(1):60–73
ADHD – Evidence based practice

MTA Study results







Positive effects of behavior therapy when combined with medications.
Most studies that compared behavior therapy to stimulants found a much
stronger effect on ADHD core symptoms from stimulants than from behavior
therapy.
The MTA study found that combined treatment (behavior therapy and stimulant
medication) was not significantly more efficacious than treatment with
medication alone for the core symptoms of ADHD after correction for multiple
tests in the primary analysis.
A secondary analysis of a combined measure of parent and teacher ratings of
ADHD symptoms revealed a significant advantage for the combination with a
small effect size.
The combined treatment compared w meds alone offered greater improvements
on academic & conduct measures when ADHD coexisted with anxiety and for
children in low SEC environments.
Parents & teachers more satisfied with treatment plan for combined therapy.
Combo of medication management & behavior therapy facilitated a lower dose of
stimulants, possibly reducing risk of side effects.
ADHD – Diagnostic Considerations

Preschool Children

Adolescents
ADHD – Differential Diagnosis















Bipolar disorder
Anxiety disorder
Depression
Absence seizures
Visual or hearing impairments
Learning disabilities and processing problems
Medication – Phenobarbital, antihistamines, anticonvulsants
Chaotic environment or classroom; Inadequate teacher, neglect or abuse -bullying
Giftedness
Pain syndromes
Endocrine, metabolic disorders. Anemia, thyroid abnormalities. Lead.
Drugs or alcohol
Language problems
Sleep disorder (apnea)
Psychosis
ADHD: Co-Morbid Conditions

Externalizing



Internalizing




ODD (30-60%) and conduct disorder (10-50%)
Intermittent explosive disorder
Anxiety disorder (10-30%)
Depression
mood disorder including bipolar
Associated Motor Deficits

Clumsiness, poor motor planning, handwriting and fine
motor difficulties and coordination problems. Difficulty
with utensils
ADHD: Co-Morbid Conditions

Associated Motor Deficits
Clumsiness
 poor motor planning
 handwriting and fine motor difficulties
 coordination problems
 Proprioception


Ex: Difficulty with utensils
ADHD: Co-Morbid Conditions

Associated Speech & Language Deficits


Early delays in speech/language acquisition
Persistent speech/language disorders

Common to ADHD and learning disabilities



receptive and expressive language deficits
weaknesses in pragmatic language skills
Impairment in auditory processing – common in children w
ADHD
 Auditory processing disorder (APD): deficit in the processing
of auditory information despite normal hearing.
 Individuals with APD typically have difficulty listening in the
presence of background noise, understanding rapid or
degraded speech, and following oral instructions.
 Recent investigations suggest a dysfunction of auditory
working memory.
ADHD: Diagnostic Evaluation

Family (parents, guardian, other frequent caregivers):









Chief concerns
History of symptoms (eg, age of onset and course over
time)
Family history
Past medical history
Psychosocial history
Review of systems
Validated ADHD instrument
Evaluation of coexisting conditions
Report of function, both strengths and weaknesses
ADHD: Diagnostic Evaluation

School (and important community
informants):
Concerns
 Validated ADHD instrument
 Evaluation of coexisting conditions
 Report on how well patients function in academic,
work, and social interactions
 Academic records (eg, report cards, standardized
testing, psychoeducational evaluations)
 Administrative reports (eg, disciplinary actions)

ADHD: Diagnostic Evaluation

Child/adolescent (as appropriate for child’s
age and developmental status):
Interview, including concerns regarding behavior,
family relationships, peers, school
 For adolescents: validated self –report instrument
of ADHD and coexisting conditions
 Report of child’s self-identified impression of
function, both strengths and weaknesses
 Clinician’s observations of child’s behavior
 Physical and neurologic examination

ADHD: Diagnostic Evaluation

Physical Examination







r/o findings that cld mimic ADHD or syndromes with a
high prevalence of ADHD behaviors
Visual acuity
Audiogram
Ht, Wt, HC, BP
Neurologic examination, expanded
Look for dysmorphic features (r/o FAS, FRAX)
Full or abbreviated neurodevelopmental screening tasks


Look for LD, language d/o,
May notice s/s of hyperactivity and/or inattentiveness resulting
from stress of tasks
ADHD: Diagnostic Evaluation
TASK
FUNCTION
Ask child to write a sentence
Written expression & dysgraphia
Ask child to tell about a movie or video
seen recently
Oral expression, memory, sequencing
Ask child to read a paragraph
Reading fluency & comprehension
appropriate for age (e.g., Grey Oral
Reading Test)
Ask child to repeat a series of random
numbers: both forward & reverse
Attention, short-term memory,
sequencing, working memory
Ask child a multiple-step task to complete Attention, memory, auditory processing
in order given
ADHD: Treatment
Medication & Behavior Therapy (eg, results of
MTA studies)
 Consider specific target outcomes to guide
management

Reflect the key symptoms of that child and specific
impairments
 Sample target outcomes –

Complying w parental commands at home
 Finishing homework and handing it in.

ADHD: Treatment
Medications:
 Most widely prescribed are the
psychostimulants: considered first line

Methylphenidate preparations
 Amphetamine preparations

Short Acting (3-6 hours)
 Intermediate acting (6-8 hours)
 Long acting (10 – 12 hours)

ADHD: Treatment

Appropriate initiation and follow-up
Initial counseling & education
 Start w low dose
 Follow weekly at first
 Titrate dose
 Periodic follow-up behavior assessment (parent &
school staff)
 Switch to another stimulant or formulation, if
necessary
 Determine the reason for treatment failure

ADHD: Treatment
Methylphenidate (mph) preparations
Amphetamine Preparations
Amphetamine Preparations
Non-Stimulants

Atomoxetine (Strattera)

Tricyclic antidepressants

Imipramine, desipramine, nortriptyline
Inhibite NE reuptake
 Limited by cardiac side effects


Bupropion (Wellbutrin and others)

Antidepressant with NE & DA properties
Non-Stimulants
Alpha-2 adrenergic agonists
 Clonidine



Long acting = Kapvay
Guanfacine

Long acting = Intuniv
Second-line preparations for ADHD
 Can be used to counteract stimulant SE’s
 For children with co-morbid aggressive behaviors
 Guanfacine can be used for children with ADHD,
tics, aggression.

Management of Side Effects
Complementary and Alternative
Therapies
Omega-3 fatty acid supplementation
 Melatonin
 Others: encourage parents to report what
they are using at home
