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• ADHD is a neurodevelopmental disorder affecting many children
• Core symptoms involve inattention and/or hyperactivity-impulsivity that impair functioning and development
• Diagnosis is outlined in the DSM-5

Diagnostic Criteria for ADHD

• Requires a persistent pattern of inattention and/or hyperactivity-impulsivity
• Symptoms must interfere with functioning or development
• The DSM-5 requires at least six symptoms of inattention or hyperactivity-impulsivity
• The behaviors must be evident prior to 12 years of age
• Behaviors must be evident in two or more settings
• The behaviors must have a clear impact on psychosocial functioning

Subtypes of ADHD

• Predominantly hyperactive/impulsive
• Predominantly inattentive
• Combined

ADHD Inattention Symptoms

• Often fails to give close attention to details or makes careless mistakes
• Often has difficulty sustaining attention
• Often does not seem to listen when spoken to directly
• Often does not follow through on instructions and fails to finish tasks
• Often has difficulty organizing tasks and activities
• Often avoids tasks that require sustained mental effort
• Often loses things necessary for tasks or activities
• Is often easily distracted by extraneous stimuli
• Is often forgetful in daily activities

ADHD Hyperactivity/Impulsivity Symptoms

• Often fidgets or squirms in seat
• Often leaves seat when remaining seated is expected
• Often runs about or climbs excessively in inappropriate situations
• Often has difficulty playing or engaging in leisure activities quietly
• Is often "on the go" or acts as if "driven by a motor"
• Often talks excessively
• Often blurts out answers before questions have been completed
• Often has difficulty awaiting turn
• Often interrupts or intrudes on others

Additional Diagnostic Considerations

• Clinicians, parents, and teachers must report at least six of nine behaviors from either the inattention or hyperactivity/impulsivity list
• For combined type ADHD, more than six symptoms must be present from both lists
• Behaviors must have an onset prior to 12 years of age and a duration of at least 6 months
• Behaviors must be evident in two or more settings like home and school
• Behaviors must have a clear impact on psychosocial functioning
• Symptoms do not occur exclusively during a pervasive disorder or are better accounted for by another mental disorder

Prevalence

• ADHD is common, with a worldwide prevalence estimated at approximately 5%
• It is one of the more common childhood disorders, representing one-third to one-half of referrals to child mental health services
• Occurs more often in boys than in girls

Developmental Course

• Symptoms may decline with age, about 40% of children continue to meet full criteria in adulthood
• Hyperactive/impulsive and combined subtypes are more common in younger children
• The disorder can progress from hyperactive/impulsive or combined to predominantly inattentive as children get older
• The first signs are developmentally inappropriate inattentive and overactive behavior, peaking between 3 and 4 years of age
• Psychosocial impairment in relationships and functioning across multiple settings becomes more apparent in middle childhood

Impacts of ADHD

• Behavioral problems around chores, self-help activities, and interactions with siblings
• Academic performance and classroom behavior are often erratic, contributing to underachievement
• Impaired relationships with teachers and peers
• Poor social skills eventually create a pattern of social rejection

Comorbidity

• ADHD is often comorbid with other psychiatric conditions, developmental and health risks, and functional impairments
• 44%-87% of children with ADHD have at least one other disorder

Psychiatric Disorders

• Oppositional defiant disorder (ODD) and conduct disorder (CD) are the most common comorbid disorders with ADHD
• About 50-60% of children with ADHD meet criteria for ODD
• Most common comorbid disorder in adolescents, ODD is characterized by negativistic, hostile, and defiant behavior
• About 25% of children meet CD criteria, which describes a pattern of behavior violating age-appropriate social norms and the rights of others

Mood and Anxiety Disorders

• Commonly observed in children with ADHD
• Anxiety disorders may exist in about 25% of children with ADHD

Tics

• 21%-90% of children with Tourette syndrome may also have ADHD
• Tics may not be exacerbated by stimulant agents

Functional Impairment

• Includes deficits in executive functions (EF), delay aversion, and temporal processing

Executive Functions (EF)

• Encompass high-order cognitive functions including working memory, cognitive flexibility, and inhibitory control
• EF deficits may manifest as forgetfulness and difficulty in planning and coordinating everyday tasks

Delay Aversion

• Evidenced by the fact that children with ADHD display a preference for smaller immediate rewards rather than larger later ones

Temporal Processing Deficits

• Slower rate at which the brain processes auditory information
• People with speech and learning disorders require 300 milliseconds to process basic speech sounds, where normal processing takes about 25 milliseconds

Social/Peer Functioning

• Children with ADHD often display impaired social performance and are more likely to be nominated by their peers as someone they would least like to be friends with
• Combined type ADHD are more aggressive and intrusive
• Inattentive type ADHD may appear withdrawn and display poorer memory of interactions

Academic Functioning

• Academic under-achievement is a common feature from pre-school through adolescence
• ADHD children are more likely to require specialist academic support or repeat a school year

Developmental Risks

• 30-50% of children with ADHD demonstrate poor motor coordination or motor performance and balance
• Difficulties in motor coordination can result in clumsiness

Health Risks

• Sleep problems occur twice as often in ADHD as in control children
• Problems include settling difficulties, longer time to fall asleep, instability of sleep duration, tiredness at awakening or frequent night waking

Etiology

• Biological explanations include genetics and brain structure
• Environmental explanations include parenting, diet, and exposure to environmental toxins

Genetics

• ADHD is considered one of the most heritable psychiatric conditions
• Genetic factors account for 80% of the etiology of ADHD
• ADHD is clustered significantly among biological relatives
• Genes involved include those regulating dopaminergic transmission such as the DAT1 gene (dopamine transporter 1) and overexpression of the DRD4/7R gene

Brain Structure

• MRI studies suggest that the brain circuit linking the pre-frontal cortex, striatum, and cerebellum are not functioning normally
• Compromised brain morphology is related to behavioral measures of inhibition and attention

Parenting Styles

• ADHD is viewed as a "gene x environment interaction"
• Children with genetic predisposition will express the disorder in a chaotic parenting environment
• Improvements in ADHD symptoms occur when parents are taught alternative parenting skills

Diet Considerations

• Large randomized control trial demonstrated a general adverse effect of food coloring agents and benzoate preservatives on hyperactive behavior

Management of ADHD

• A combination of pharmacological and psychosocial treatment provides better long-term outcomes

Pharmacological Treatment

• Stimulants like methylphenidate and lisdexamphetamine dimesylate (LDX)
• Non-stimulants like atomoxetine (ATX)
• Anticonvulsants, atypical antipsychotics or lithium for comorbid conditions like CD or ODD

Methylphenidate

• CNS stimulant prescribed under specialist supervision
• Blocks the reuptake of norepinephrine and dopamine
• Increase release of these monoamines into the extra-neuronal space
• Available in modified-release formulations that enable once-daily dosing, also available as transdermal delivery patch

Extended Release Stimulants

• Provides continuous coverage for controlling ADHD symptoms throughout the school day

Transdermal System

• Minimizes the potential for diversion

Common Adverse Effects of Treatment

• Insomnia, nervousness, headache, decreased appetite
• Abdominal pain and cardiovascular effects such as tachycardia, palpitations and minor increases in blood pressure
• Treatment initiated at a dose of 18 mg once daily, maximum of 54 mg once daily

Atomoxetine (ATX)

• Non-stimulant medication approved for use in the treatment of ADHD
• Updated guidelines recommend ATX as a first-line treatment option
• Generally takes longer to have a full effect: ATX is dispensed in capsules of 10, 18, 25, 40, 60, 80, and 100 mg
• Mechanism of action is related to inhibition of the presynaptic norepinephrine transporter
• The maximum daily dose approved by the US FDA for children and adolescents who weight ≤ 70 Kg is 1.4 mg/kg/day, 100mg/day if over
• Tapering is not necessary when discontinuing ATX

Common Adverse Effects

• Abdominal pain, decreased appetite, nausea and vomiting
• Early morning awakening, irritability, mood swings
• Increased heart rate and small increases in blood pressure

Methylphenidate-Containing Products

• Includes various immediate and extended-release formulations
• Duration of effects vary, ranging from 3 to 12 hours

Amphetamine-Containing Products

• Mixed amphetamine salts immediate and extended release
• Lisdexamfetamine dimesylate

Norepinephrine Reuptake Inhibitor

• Atomoxetine
• May be considered first-line therapy for children with active substance abuse problem
• Comorbid anxiety or tics

Alpha-Adrenergic Receptor Agonists

• Clonidine and Guanfacine extended release
• May be more effective for hyperactivity than inattention

Available Pharmacologic Agents

• Some children respond better to one stimulant type than another
• Ramp effect: Behavioral effects are proportional to the rate of methylphenidate absorption into the central nervous system

Adverse Effects and Precautions

• Headache, stomachache, loss of appetite, and insomnia
• Use with caution in patients with glaucoma, tics, psychosis, and concomitant monoamine oxidase inhibitor use
• Insomnia, anorexia, and tics occur more often with transdermal patch, also mild skin reactions

Potential Association of Stimulants with Sudden Cardiac Death (SCD)

• The frequency of SCD is no higher in children taking stimulants
• The AAP recommends targeted cardiac history and physical examination
• Routine electrocardiography is not recommended unless history and physical examination suggest cardiac disease

Non-Stimulant Medications

• Norepinephrine reuptake inhibitors
• Adverse effects: Dyspepsia, decreased appetite, weight loss, and fatigue
• Black box warning about increased risk of suicidal ideation in children and adolescents
• Does not exacerbate tics

Alpha-Adrenergic Receptor Agonists

• Antidepressants:
  • Non-FDA label approved for the treatment of ADHD
  • Noradrenergic antidepressant (e.g., bupropion [Wellbutrin])
  • Baseline electrocardiogram is recommended, desipramine should be used with extreme caution

Non-Pharmacological Treatment

• Parenting interventions
• Classroom interventions
• Child psychosocial therapy