What is the pathophysiology and treatment approach for Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients?

ADHD Disease Process and Treatment

Pathophysiology

ADHD is a neurodevelopmental disorder characterized by dysfunction in prefrontal cortex executive functions, with impaired dopamine and norepinephrine neurotransmission in frontal-striatal pathways. 1

• The prefrontal cortex controls executive functions including planning, impulse control, working memory, and sustained attention—all of which are impaired in ADHD 1
• PET scanning demonstrates 8.1% lower cerebral glucose metabolism in untreated adults with ADHD, with greatest reductions in superior prefrontal cortex and premotor areas 1
• Stimulant medications bind to dopamine transporters in the striatum, increasing synaptic dopamine and norepinephrine, which enhances executive control processes and ameliorates deficits in inhibitory control and working memory 1
• The disorder manifests as persistent inattention, hyperactivity, and impulsivity that causes functional impairment across multiple life domains 1

Critical caveat: No single neuropsychological test, genetic marker, or neuroimaging finding is pathognomonic for ADHD—diagnosis remains clinical based on DSM-5 criteria 2

Diagnostic Criteria

Diagnosis requires meeting DSM-5 criteria: at least 6 symptoms of inattention and/or hyperactivity-impulsivity (5 for adolescents ≥17 years) persisting ≥6 months, onset before age 12, and documented functional impairment in at least 2 settings (home, school, work, social). 1, 3

• Obtain standardized rating scales from multiple observers—parents, teachers, and the patient when possible—combined with comprehensive clinical history 3
• Rule out alternative causes including mood disorders, anxiety, sleep disorders, learning disabilities, and substance use 1, 4
• Screen for common comorbidities present in 12-60% of cases: anxiety disorders, depression, oppositional defiant disorder, conduct disorder, learning disabilities, and tics 1, 3, 2

Treatment Algorithm by Age

Preschool Children (Ages 4-5 Years)

Prescribe evidence-based parent-administered and/or teacher-administered behavior therapy as first-line treatment. 1, 3

• Behavior therapy involves training parents in specific techniques: positive reinforcement for desired behaviors, planned ignoring for unwanted behaviors, and appropriate consequences when goals are not met 1
• Add methylphenidate only if behavioral interventions provide insufficient improvement and moderate-to-severe functional impairment persists 1, 3
• Weigh risks of starting medication before age 6 against harm of delaying treatment when behavioral therapy is unavailable 1

Elementary School Children (Ages 6-11 Years)

Prescribe FDA-approved stimulant medications (methylphenidate or amphetamine preparations) as first-line pharmacotherapy, combined with behavioral parent training and classroom behavioral interventions. 1, 3

• Stimulants produce the strongest effects on core ADHD symptoms with effect sizes around 1.0, significantly outperforming behavioral therapy alone 3
• More than 70% of children respond optimally to one stimulant medication when systematic titration is used 3
• The MTA study demonstrated combined treatment (medication + behavior therapy) offered greater improvements on academic and conduct measures when ADHD coexisted with anxiety or in low socioeconomic environments 1
• Combined treatment allows lower stimulant dosages, reducing adverse effect risk 1
• Parents and teachers report significantly greater satisfaction with combined therapy 1

Medication hierarchy by evidence strength: Stimulants (methylphenidate or amphetamine) have the strongest evidence, followed by atomoxetine, extended-release guanfacine, then extended-release clonidine 1

Adolescents (Ages 12-18 Years)

Prescribe FDA-approved ADHD medications with the adolescent's assent, preferably combined with evidence-based behavioral interventions targeting organizational skills and time management. 1, 3

• Before initiating medication, assess for substance use symptoms; if active use is identified, refer to subspecialist for consultative support 1
• Monitor prescription refill requests for signs of medication misuse or diversion to parents, classmates, or acquaintances 1, 5
• Provide medication coverage for symptom control while driving using longer-acting or late-afternoon short-acting medications 1

Medication Management Protocol

Titration Strategy

Titrate doses to achieve maximum benefit with minimum adverse effects rather than using strict weight-based dosing, with weekly assessment during initial titration. 3

• For pediatric patients ≥6 years: start methylphenidate 5 mg twice daily before breakfast and lunch (30-45 minutes before meals), increase by 5-10 mg weekly, maximum 60 mg daily 5
• For adults: administer 2-3 times daily 30-45 minutes before meals, average dose 20-30 mg daily, maximum 60 mg daily 5
• If medication taken late causes insomnia, administer last dose before 6 PM 5

Monitoring Schedule

Assess treatment response using standardized parent and teacher rating scales: weekly during dose titration, monthly during first 3-6 months, then every 3-6 months once stable. 3

• Monitor common stimulant adverse effects: appetite loss, abdominal pain, headaches, sleep disturbance, and growth velocity (1-2 cm reduction over time) 3
• If paradoxical aggravation or adverse reactions occur, reduce dosage or discontinue 5
• If no improvement after appropriate dosage adjustment over one month, discontinue 5

School-Based Interventions

Educational interventions and individualized instructional supports are necessary components of any ADHD treatment plan, formalized through an IEP or 504 Rehabilitation Plan. 1, 3

• Classroom adaptations include preferred seating, modified work assignments, test modifications (location and time), and behavioral plans 1, 3
• Children with ADHD qualify as children with special health care needs requiring chronic care model management 1

Critical Warnings

Methylphenidate has high potential for abuse and misuse leading to substance use disorder; assess each patient's risk before prescribing and monitor throughout treatment for signs of abuse, misuse, or diversion. 5

• Contraindicated in patients receiving MAOIs or within 14 days of MAOI discontinuation due to hypertensive crisis risk 5
• Contraindicated in patients with known hypersensitivity to methylphenidate (angioedema and anaphylaxis reported) 5
• Assess for cardiac disease (careful history, family history of sudden death or ventricular arrhythmia, physical exam) before treatment 5
• Evaluate family history and clinically assess for motor/verbal tics or Tourette's syndrome before treatment 5