Attention Deficit Hyperactivity Disorder (ADHD) in Children

1. Definition and Epidemiology

• Prevalence: 6-9% of children and adolescents worldwide; the DSM-5 conservatively estimates ~5% in children. The US National Survey of Children's Health reports 9.4% among 2- to 17-year-olds.
• Sex ratio: Boys are more likely to be diagnosed, and earlier, than girls. Girls more commonly present with the inattentive subtype, which is more easily missed.
• Persistence: Roughly 50% of affected children continue to meet diagnostic criteria into adulthood. Most affected children continue to meet criteria through adolescence.
• Bradley and Daroff's Neurology in Clinical Practice, p. 1407
• The Harriet Lane Handbook, 23rd ed., p. 820

2. Etiology

A. Genetic Factors

• Heritability of ADHD ranges from 0.70 to 0.88 in twin studies, making it one of the most heritable psychiatric conditions.
• Approximately one-quarter of first-degree relatives of a child proband with ADHD also has or had ADHD.
• ADHD co-occurs with other neurobehavioral disorders such as Tourette syndrome, OCD, anxiety disorders, and learning disabilities, raising the possibility of shared susceptibility genes.
• Specific causative genes have not yet been definitively identified; genome-wide association meta-analyses have been largely inconclusive to date.

B. Neurobiological Factors

• Neuropsychological deficits in ADHD are consistent with dysfunction of basal ganglia-frontal circuits.
• Core proposed deficits include:
  • Failure of inhibitory control
  • Dysregulation of brain systems mediating reward and response cost
  • Deficits in arousal, activation, and effortful control
• The key neurotransmitters implicated are dopamine (DA) and norepinephrine (NE). Stimulant medications (methylphenidate, amphetamines) work by blocking or reversing dopamine and norepinephrine transporters in the prefrontal cortex and striatum.

C. Environmental and Medical Factors

• Prenatal exposure to tobacco, alcohol, or lead
• Prematurity: ADHD occurs in approximately 20% of preterm infants
• High co-occurrence with epilepsy (up to 30% in childhood epilepsy with centrotemporal spikes, BECTS)
• Adverse childhood events (ACEs) and trauma can produce an ADHD-like presentation
• Perinatal hypoxia, infections, and head trauma are also recognized contributing factors

D. Other Factors

• People with ADHD are relatively more likely to use nicotine products; tobacco smoke contains MAOIs which may temporarily benefit ADHD symptoms - though this is not a treatment
• Psychosocial factors (e.g., family conflict, institutional upbringing) can worsen severity but do not cause ADHD alone
• Bradley and Daroff's Neurology in Clinical Practice, pp. 1537-1543
• The Maudsley Prescribing Guidelines in Psychiatry, 15th ed., p. 934

3. Clinical Features

A. Inattention Symptoms (DSM-5)

1. Fails to give close attention to details or makes careless mistakes in schoolwork
2. Has difficulty sustaining attention in tasks or play
3. Does not seem to listen when spoken to directly
4. Does not follow through on instructions; fails to finish schoolwork or chores
5. Has difficulty organizing tasks and activities
6. Avoids or is reluctant to engage in tasks requiring sustained mental effort (e.g., homework)
7. Loses things necessary for tasks or activities (pencils, books, keys)
8. Is easily distracted by extraneous stimuli
9. Is often forgetful in daily activities

B. Hyperactivity-Impulsivity Symptoms (DSM-5)

1. Fidgets or squirms in seat
2. Leaves seat in situations where remaining seated is expected
3. Runs about or climbs in inappropriate situations (in adolescents, may be just restlessness)
4. Cannot play or engage in leisure activities quietly
5. Is "on the go" as if "driven by a motor"
6. Talks excessively
7. Blurts out answers before questions have been completed
8. Has difficulty awaiting turn
9. Interrupts or intrudes on others

C. DSM-5 Subtypes

D. Preschool Nuances (Additional Signs in Young Children)

• High activity level, poor persistence and follow-through
• Problems staying with the class during group activities
• Over-eager physical play; silliness unusual for age
• Requires constant supervision
• Anxiousness/difficult behavior when required to wait
• Toileting accidents due to forgetfulness

E. Severity Classification

• Mild: Few or no symptoms beyond what is needed for diagnosis; minor impairments
• Moderate: Functional impairment between mild and severe
• Severe: Many excess symptoms, several particularly severe, or marked impairment in social/occupational functioning

F. Comorbidities

• Oppositional Defiant Disorder (ODD) and Conduct Disorder
• Anxiety disorders and depression
• Learning disabilities
• Tic disorders and Tourette syndrome
• Sleep difficulties
• Bradley and Daroff's Neurology in Clinical Practice, pp. 1403-1540
• The Harriet Lane Handbook, 23rd ed., p. 820

4. Diagnosis

A. DSM-5 Core Requirements (All Must Be Met)

1. Symptom count: ≥6 symptoms of inattention AND/OR ≥6 symptoms of hyperactivity-impulsivity (≥5 if age ≥17)
2. Duration: Symptoms persist for at least 6 months
3. Age of onset: Several symptoms present before age 12 years
4. Multiple settings: Symptoms present in ≥2 settings (e.g., home and school)
5. Functional impairment: Symptoms interfere with or reduce quality of academic, social, or occupational functioning
6. Developmental inappropriateness: Symptoms are excessive for the developmental level
7. Exclusions: Symptoms do not occur exclusively during schizophrenia or another psychotic disorder, and are not better explained by another mental disorder

B. Evaluation Tools

• Vanderbilt Diagnostic Rating Scales (parent and teacher versions) - recommended for all children with academic or behavioral concerns. Can also monitor treatment response.
• Behavioral questionnaires should be obtained from both parents and teachers, as symptoms must be present in multiple settings
• Psychological and neuropsychological testing is not required for diagnosis but is recommended when academic or developmental concerns are also present
• If medical history is unremarkable, no laboratory or other specific testing is required

C. Differential Diagnosis

• Conduct disorder
• Oppositional Defiant Disorder (ODD)
• Anxiety disorder
• Depression
• Learning disorder
• Adverse childhood events / trauma (can produce an ADHD-like picture)
• Thyroid disease, anemia, hearing/vision impairment, sleep disorders
• Absence epilepsy (can mimic inattentive ADHD)

• The Harriet Lane Handbook, 23rd ed., pp. 820-821
• Bradley and Daroff's Neurology in Clinical Practice, p. 1405

5. Management

A. Behavioral and Psychosocial Interventions

• Behavioral therapy is recommended as an adjunct to pharmacologic treatment and works best in combination with medication.
• For preschool-aged children (4-5 years old), behavioral therapy alone should be tried first before initiating stimulant medication.
• Parent training in behavior management is a core component
• School-based accommodations (extended test time, preferential seating, reduced distraction environments)
• Evidence-based behavioral management includes contingency management, token economies, and social skills training

B. Pre-Treatment Cardiac Screening

• Take a cardiac history to exclude: cardiac symptoms, Wolff-Parkinson-White syndrome, family history of sudden cardiac death, hypertrophic cardiomyopathy, and long QT syndrome
• If positive cardiac history: refer to cardiologist before initiating treatment
• Screening ECG is NOT required if there is no personal or family history of cardiac disease

C. Pharmacologic Treatment

First-Line: Stimulant Medications

• 65-75% of stimulant-treated youth respond
• Response rates are similar for methylphenidate and amphetamine preparations
• Extended-release (ER) formulations are first-line - they enhance adherence, provide sustained symptom control, and have lower abuse potential than immediate-release (IR) preparations
• A "booster" dose of immediate-release stimulant in the afternoon is not uncommon when ER preparations are used

• Adequate methylphenidate trial: >0.8 mg/kg/day
• Adequate amphetamine trial: ≥0.5 mg/kg/day
• Titrate to maximal symptom control with minimal side effects; symptom control is expected within 1 week of initiation
• No buildup period needed; titrations can be made weekly

Second-Line / Non-Stimulant Options

• In youth with partial response to stimulants, adding guanfacine or clonidine may boost ADHD response
• α-agonists are supported by multiple RCTs as monotherapy and combination therapy

Other Adjunctive/Off-Label Agents

• Bupropion (useful when ADHD co-occurs with depression)
• Tricyclic antidepressants (second-line; cardiac monitoring required)
• SSRIs (for comorbid anxiety or depression)
• Modafinil (non-stimulant wakefulness agent)

D. Common Side Effects of Stimulants

• Appetite suppression (most common) - can affect growth velocity
• Abdominal pain and headaches
• Palpitations; mild increases in heart rate and blood pressure
• Sleep dysregulation (insomnia)
• Emotional lability / irritability
• Rebound effects as medication wears off

E. Monitoring Treatment Response

• Vanderbilt scales can be re-administered to monitor behavioral changes
• Monitor height, weight, heart rate, and blood pressure at each visit
• Monthly physician follow-up during titration phase is ideal (as per the MTA study protocol)

F. Key Clinical Trials Informing Practice

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry, pp. 10370, 11967-11970
• The Harriet Lane Handbook, 23rd ed., pp. 820-821
• Bradley and Daroff's Neurology in Clinical Practice, pp. 1601-1617

Summary Table