Attentiondeficit hyperactivity disorder ADHD

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Attention-deficit / hyperactivity disorder ADHD

• Nazir Kayali MD. FAAP.
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Attention-deficit/hyperactivity disorder ADHD

• is the most common neurobehavioral disorder of
  childhood
• One of the most prevalent chronic health
  condition affecting school-aged children
• The most extensively studied mental disorder of
  childhood

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• Epidemiology

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Epidemiology

• Studies of the prevalence of ADHD across the
  globe have generally reported that 5-10 of
  school-aged children are affected.
• although rates vary considerably by country,
  perhaps in part due to differing sampling and
  testing techniques.

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Epidemiology

• The prevalence rate in adolescent samples is
  2-6.
• Approximately 2 of adults have ADHD

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Epidemiology

• ADHD is often underdiagnosed in children and
  adolescents.
• Youth with ADHD are often undertreated with
  respect to what is known about the needed and
  appropriate doses of medications.

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• PATHOGENESIS

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PATHOGENESIS

• Functional MRI findings suggest
• 1- low blood flow to the striatum.

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PATHOGENESIS

• 2- a smaller brain volumes of specific
  structures, such as the prefrontal cortex and
  basal ganglia. Children with ADHD have
  approximately a 5-10 reduction in these brain
  structures.
• The prefrontal cortex and basal ganglia are rich
  in dopamine receptors.

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PATHOGENESIS

• This knowledge, plus data about the dopaminergic
  mechanisms of action of medication treatment for
  ADHD, has led to the dopamine hypothesis, which
  postulates that disturbances in the dopamine
  system may be related to the onset of ADHD

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• ETIOLOGY

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ETIOLOGY

• Multiple factors have been implicated in the
  etiology of ADHD.
• many unknowns

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ETIOLOGY / genetic

• There appears to be a strong genetic component to
  ADHD
• family history of ADHD, alcoholism, sociopathy,
  mood and anxiety disorders

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ETIOLOGY / genetic

• It was found that over 25 of the first-degree
  relatives of the families of ADHD children also
  had ADHD, whereas this rate was only about 5 in
  each of the control groups.
• Therefore, if a child has ADHD there is a
  five-fold increase in the risk to other family
  members.

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ETIOLOGY / genetic

• Approximately half of parents who have been
  diagnosed with ADHD themselves, will have a child
  with the disorder.

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ETIOLOGY / genetic

• They reported an 82 percent concordance rate for
  ADHD in identical twins as compared to a 38
  percent concordance rate for ADHD in
  non-identical twins.

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ETIOLOGY / Medical

• Mothers of children with ADHD are more likely to
  experience birth complications, such as toxemia,
  lengthy labor, and complicated delivery.

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ETIOLOGY / Medical

• children with severe traumatic brain injury are
  reported to have subsequent onset of substantial
  symptoms of impulsivity and inattention.
• CNS infections

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ETIOLOGY / Exposure

• Exposure to toxins, such as maternal smoking or
  alcohol use and postnatal exposure to lead, has
  also traditionally been correlated with ADHD

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ETIOLOGY / Exposure

• In a study that assessed hyperactivity behaviors,
  297 3-9 year-old were given drinks containing
  either placebo or artificial food coloring mixes.
  Children who received the artificially colored
  beverages had statistically significant
  hyperactivity scores.
• only some hyperactive children would respond
  favorably to elimination

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ETIOLOGY / Psychosocial

• family stressors may also contribute to or
  exacerbate the symptoms of ADHD.

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ETIOLOGY / Cultural

• much lower prevalence estimates in Europe and
  Japan than US

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• CLINICAL MANIFESTATIONS
• Diagnosis

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CLINICAL MANIFESTATIONS

• Three Sub-Types of ADHD
• Predominantly hyperactive type
• Predominantly inattentive type
• Mixed Type

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Diagnosis

• Parent interview is core assessment
• Obtain academic, behavioral, psychoeducational
  testing, and attendance reports from school
• Use parent and teacher rating scales (when
  possible)
• Complete medical history and physical examination
• Evaluate for comorbidity

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Diagnosis

• According to the 4th edition of the American
  Psychiatric Association's Diagnostic and
  Statistical Manual (DSM-IV), ADHD is
  characterized by
• (1) inattention, including increased
  distractibility and difficulty sustaining
  attention
• (2) poor impulse control and decreased
  self-inhibitory capacity
• (3) motor overactivity and motor restlessness

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Diagnosis

• DSM-IV diagnostic criteria for ADHD (American
  Psychiatric Association's diagnostic and
  statistical manual )
• 1- Developmentally inappropriate levels of
  inattention, hyperactivity, and impulsivity that
  begin in childhood and
• 2- cause impairment in school performance,
  intellectual functioning, social skills, driving,
  and occupational functioning
• 3 onset lt7 years of age (childhood onset)
• 4 disturbance lasting gt6 month

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Diagnosis

• 5 cross-situational (home, school, work)
• 6- Symptoms do not occur exclusively during the
  course of a pervasive developmental disorder (
  PDD ), schizophrenia, or other psychotic disorder
• 7- must not be secondary to another disorder
  (e.g., mood disorder, anxiety disorder,
  dissociative disorder, personality disorder)

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Diagnosis / Inattention

• Six (or more) of the following symptoms

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Diagnosis / Inattention

• 1- Often fails to give close attention to details
  or makes careless mistakes in schoolwork, work,
  or other activities
• 2- Often has difficulty sustaining attention in
  tasks or play activities
• 3- Often does not seem to listen when spoken to
  directly

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Diagnosis / Inattention

• 4- Often does not follow through on instructions
  and fails to finish schoolwork, chores, or duties
  in the workplace (not due to oppositional
  behavior or failure to understand instructions)
• 5- Often has difficulty organizing tasks and
  activities
• 6- Often avoids, dislikes, or is reluctant to
  engage in tasks that require sustained mental
  effort (such as schoolwork or homework)

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Diagnosis / Inattention

• 7- Often loses things necessary for tasks or
  activities (e.g., toys, school assignments,
  pencils, books, tools)
• 8- Is often easily distracted by extraneous
  stimuli
• 9- Is often forgetful in daily activities

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Diagnosis / Hyperactivity

• Six (or more) of the following symptoms of
  hyperactivity-impulsivity

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Diagnosis / Hyperactivity

• 1- Often fidgets with hands or feet or squirms in
  seat
• 2- Often leaves seat in classroom or in other
  situations in which remaining seated is expected
• 3- 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)

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Diagnosis / Hyperactivity

• 4- Often has difficulty playing or engaging in
  leisure activities quietly
• 5- Is often "on the go" or often acts as if
  "driven by a motor"
• 6- Often talks excessively

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Diagnosis / Hyperactivity

• Impulsivity
• 7- Often blurts out answers before questions have
  been completed
• 8- Often has difficulty awaiting turn
• 9- Often interrupts or intrudes on others (e.g.,
  butts into conversations or games)

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• Differential
• Diagnosis

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Differential Diagnosis

• 1- Chronic illnesses (migraine headaches, absence
  seizures, asthma and allergies, hematologic
  disorders, diabetes, childhood cancer, itch)
  affect up to 20 of children in the U.S.
• 2- substance abuse may result in declining school
  performance and inattentive behavior.

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Differential Diagnosis

• 3- Sleep disorders, including those secondary to
  chronic upper airway obstruction from enlarged
  tonsils and adenoids, frequently result in
  behavioral and emotional symptoms
• 4- Depression and anxiety disorders may cause
  many of the same symptoms as ADHD but, may also
  be comorbid conditions.

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Differential Diagnosis

• 5- Obsessive-compulsive disorder may mimic ADHD,
  particularly when recurrent and persistent
  thoughts, impulses, or images are intrusive and
  interfere with normal daily activities
• 6- Adjustment disorders secondary to major life
  stresses or parent-child relationship disorders

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Differential Diagnosis

• 7- Vision and hearing problems
• 8- Developmental or learning problems language
  deficits

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• Comorbidity

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Comorbidity

• The National Institute of Mental Health reported
  that
• 1) 15-25 of children with ADHD also have
  learning disabilities
• 2) 30-35 also have language disorders
• 3) 15-20 are also diagnosed with mood disorders
  
• 4) 20-25 have coexisting anxiety disorders
• 5) Also many associated medical issues tics,
  seizure disorder, etc

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• TREATMENT

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TREATMENT

• Psychosocial Treatments
• Behavior management
• Medications

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Treatment \ Psychosocial

• the parents and child should be educated with
  regard to the ways in which ADHD can affect
  learning, behavior, self-esteem, social skills,
  and family function.
• The clinician should set goals for the family to
  improve the child's interpersonal relationships,
  develop study skills, and decrease disruptive
  behaviors.

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TREATMENT \ Behavior management

• The goal of such treatment is for the clinician
  to identify targeted behaviors that cause
  impairment in the child's life
• and for the child to work on progressively
  improving his or her skill in these areas.
• The clinician should guide the parents and
  teachers in implementing rules, consequences, and
  rewards to encourage desired behaviors.

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TREATMENT

• Psychosocial Treatments
• Behavior management
• Medications

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Which Treatment Is Best forADHD?

• 540 children with ADHD for 24 months
• Medication alone was superior to all other
  treatments and equivalent or superior to any
  combination
• Behavior management was inferior to medication
• Although no improvement in performance was found
  with combined medication and behavior therapy,
  parents liked the addition of behavior therapy.
• Information Taken From Pediatrics 2004
  113754-761, Pediatrics 2004 113762-769

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TREATMENT / Medications

• The most widely researched medications used in
  the treatment of ADHD are the psychostimulant
  medications, including
• methylphenidate
• amphetamine, and/or various dextroamphetamine
  preparations

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TREATMENT / Psychostimulants

• Methylphenidate (MPH) and Mixed Amphetamine Salts
  (MAS)
• Remain treatment of choice
• Similar mechanism of action
• Slow reuptake of DA and NE
• MAS also release more NE

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TREATMENT methylphenidate compunds

• Ritalin
• Focalin, Focalin XR (d-MPH)
• Concerta (OROS-MPH)
• Metadate CD (biphasic), ER (extended)
• Ritalin LA (biphasic release)
• Ritalin SR (extended release)
• Methylin (liquid)
• Daytrana (transdermal MPH patch)

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TREATMENTAmphetamine salts compounds

• Adderall
• Adderall XR
• Vyvanse (prodrug of Adderall XR)
• Dextroamphetamine (dexedrine)

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Treatment

• The clinician should prescribe a stimulant
  treatment, either methylphenidate or an
  amphetamine compound.

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Treatment

• Over the first 4 wk, the physician should
  increase the medication dose as tolerated
  (keeping side effects minimal to absent) to
  achieve maximum benefit

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Treatment

• If this strategy does not yield satisfactory
  results, or if side effects prevent further dose
  adjustment in the presence of persisting
  symptoms, the clinician should use an alternative
  class of stimulants that was not used previously.

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Treatment

• Approximately 80 of children will respond
  favorably to one of them with satisfactory relief
  of major symptoms of ADHD

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TREATMENT Stimulant Adverse Events (AE)

• Mostly well-tolerated and AE improve with time
• Increased in younger children, neuroatypical
  (Autism/PDD, MR, brain-injured)

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TREATMENT Stimulant Adverse Events (AE)

• Most common anorexia/weight loss, insomnia,
  headache, abdominal pain, dry mouth (caries)
• Possible tics, picking/biting (OCD),
  anxiety/agitation, emotional changes (flatness,
  irritability, lability, depression/SI),
  hyperfocused (zombie), cardiovascular,
  sedation, skin changes
• Rare psychosis (hallucinations), sudden cardiac
  death (pre-existing condition)

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TREATMENT Stimulant Adverse Events (AE)

• These adverse symptoms usually remit when the
  dosage is lowered, or when an alternative
  stimulant preparation or another class of
  medication is used

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Treatment Non Stimulant

• If satisfactory treatment results are not
  obtained with the 2nd stimulant, clinicians may
  choose to prescribe atomoxetine

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TreatmentStrattera (atomoxetine)

• Selective norepinephrine reuptake inhibitor
• Slow onset, less robust, add-on to stimulants
• May help comorbid anxiety

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Treatment Strattera (atomoxetine)

• Atomoxetine should be initiated at a dose of 0.3
  mg/kg/day and titrated over 1-3 wk to a maximum
  dose of 1.2-1.8 mg/kg/day.

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TreatmentStrattera (atomoxetine)

• Side effects include hypertension, decreased
  appetite, weight loss, abdominal pain, nausea,
  vomiting, dizziness, sleepiness, fatigue Do not
  use with MAOI

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Other medications

• Wellbutrin (Bupropion)
• TricyclicAntidepressants
• Provigil (Modafanil)
• SNRI Antidepressants
• Central Alpha-2Agonists

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Treatment

• regular medication follow-up visits should be
  offered (4 or more times/yr)

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Treatment

• It should be noted that medication alone is not
  always sufficient to treat ADHD in children,
  particularly in instances where children have
  multiple psychiatric disorders or stressed home
  environments.

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Treatment

• When children do not respond to medication, it
  may be appropriate to refer them to a mental
  health specialist.

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• PROGNOSIS

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PROGNOSIS

• A childhood diagnosis of ADHD often leads to
  persistent ADHD throughout the life span.

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PROGNOSIS

• From 60-80 of children diagnosed with ADHD
  continue to experience symptoms in adolescence
• and up to 40-60 of adolescents exhibit ADHD
  symptoms into adulthood.

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PROGNOSIS

• In children diagnosed with ADHD, a reduction in
  hyperactive behavior often occurs with age.
• However, other symptoms associated with ADHD can
  become more prominent with age, such as
  inattention, impulsivity, and disorganization,
  and these exact a heavy toll on young adult
  functioning.

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PROGNOSIS

• A variety of risk factors can affect children
  with untreated ADHD as they become adults.

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PROGNOSIS / Risks

• These risk factors include
• Engaging in risk-taking behaviors (sexual
  activity, delinquent behaviors, substance use),
• Educational underachievement or employment
  difficulties
• Relationship difficulties.

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PROGNOSIS / Drug abuse

• 140 persons with ADHD vs. 120 controls at least
  age 15 years
• ADHD patients did not abuse stimulants
• Drug abuse was found in
• - 75 of unmedicated ADHD patients
• - 25 of medicated ADHD patients
• - 20 of controls
• Comorbidity increased substance abuse

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PROGNOSIS / Driving- injuries

• - Driving 2 to 4 times more likely to have MVA
• - Accidents are due to inattention not sleepiness
• - Accidents occur largely at night (worse between
  8 and 11 PM)
• J Nerv Ment Dis 2000
  188230-234
• - 3 times more likely to incur injuries of any
  sort
• Pediatr 1998
  1021415-1421

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• Summary

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Important Points about ADHD

• 1- Chronic condition affecting around 7
• of children and some adults
• 2- Strict attention to diagnostic criteria is
• required
• 3- Look for comorbidities
• 4- Team approach child, parents,
• physician, school personnel, psychologist,
• behavioral therapist

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Important Points about ADHD

• 5- Medication is a cornerstone of
• treatment
• 6- Behavior therapy may help some
• 7- Set targets reassess if targets are
• unmet
• 8- Reevaluate periodically 3 to 4 times a
• year at minimum

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• Questions ???

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Clinical presentation Preschool (ages 35)

• Motor restlessness (as if driven by a motor)
• Difficulty completing developmental tasks (eg,
  toilet training)
• Decreased and/or restless sleep
• Insatiable curiosity
• Family difficulties (eg, obtaining and keeping
  babysitters)
• Vigorous and often destructive play
• Demanding of parental attention, argumentative
• Delays in motor or language development
• Excessive temper tantrums (more severe and
  frequent)
• Low levels of compliance (especially in boys)

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Clinical presentation School-age (ages 612)

• Easily distracted
• Unable to sustain attention
• Homework is disorganized, incomplete, contains
  careless errors
• Blurts out answers before question is completed
  (often disruptive in class)
• Often interrupts or intrudes on others
• Often out of seat, acts like the class clown
• Perception of immaturity (unwilling or unable
  to complete chores at home)

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Clinical presentation Adolescent (ages 1318)

• Excessive motor activity tends to decrease
• May have a sense of inner restlessness (rather
  than hyperactivity)
• School work disorganized and shows poor
  follow-through fails to work independently
• Engaging in risky behaviors (speeding and
  driving mishaps)
• Difficulty with authority figures
• Poor self-esteem
• Poor peer relationships
• Anger, emotional lability

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Clinical presentation Adulthood

• Disorganized, fails to plan ahead
• Forgetful, loses things
• Difficulty in initiating and finishing projects
  or tasks
• Misjudges available time
• Makes impulsive decisions related to spending
  money, travel, jobs, or social plans
• Inattention/concentration problems
• Poor anger control
• May have job instability and marital difficulties

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PROGNOSIS

• With proper treatment, the risks associated with
  the disorder can be significantly reduced.

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Epidemiology

• Rates may be higher if symptoms (inattention,
  impulsivity, hyperactivity) are considered in the
  absence of functional impairment.

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Wellbutrin (Bupropion)

• Antidepressant that target norepinephrine
  reuptake and dopamine neurotransmission
• Not a first-line treatment (comorbid depression)
• Adverse events

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TricyclicAntidepressants

• Imipramine (Tofranil)
• Desipramine (Norpramin)
• Nortriptyline (Pamelor)
• AE (cholinergic, histaminergic, noradrenergic,
  quinidine-like, overdose risk)
• Overall, no longer first- or second-line options

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Provigil (Modafanil)

• Non-stimulant CNS acting compound
• Approved to treat sleep disorders (narcolepsy)
  but used off-label
• Better as add-on to first-line medication
• For ADHD or comorbidity
• Motivation spark, wakefulness, cognition
• Adverse events (including SJS, interactions OCs)

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SNRI Antidepressants

• Effexor XR, Cymbalta, Pristiq
• Affect serotonin and norepinephrine reuptake
• Similar role as Wellbutrin (more AE)

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Central Alpha-2Agonists

• Clonidine (Catapres)
• Tenex (Guanfacine)
• Intuniv (Guanfacine Extended Release)
• Approved for ADHD
• Role target hyperactivity/impulsivity, tics,
  insomnia (as primary or secondary)
• AE sedation/somnolence, less with Tenex, rebound
  hypertension, ?EKG

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New and EmergingPharmacotherapies in ADHD

• Stimulants
• Daytrana(MTS-patch)
• Amphetamine prodrug (Vyvanse)

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New and EmergingPharmacotherapies in ADHD

• Non-stimulants
• Modafanil
• Guanfacine ER
• Oral neuronal nicotinic modulator
• Reboxetine
• Novel DA-NE Ri

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Pervasive developmental disorders

• PDD include
• Autistic disorder
• Asperger disorder
• Childhood disintegrative disorder
• Rett disorder