Epidemiology
Etiology
Pathophysiology
- Neurodevelopmental disorder characterized by dysregulation of catecholamines (dopamine [DA] & norepinephrine [NE]) in the prefrontal cortex.
- Strong genetic component; frequently associated with variants in dopamine transporter genes (DAT1).
- Environmental risk factors: maternal smoking or alcohol use during pregnancy, low birth weight.
Clinical features
- Core Features: A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development.
- Inattention: Difficulty sustaining attention, makes careless mistakes, doesn’t seem to listen, trouble organizing tasks, avoids sustained mental effort, loses things, easily distracted, forgetful.
- Hyperactivity/Impulsivity: Fidgets, leaves seat when sitting is expected, runs/climbs inappropriately, unable to play quietly, often “on the go,” talks excessively, blurts out answers, difficulty waiting turns, interrupts others.
- Symptoms occur in at least 2 settings (home, school) & cause functional impairment
- Patients generally have normal intelligence, but school/work performance is impaired due to symptoms.
Diagnostics
- DSM-5 Diagnostic Criteria:
- Symptom Count:
- Children (<17 yo): ≥6 symptoms in either category (or both for combined).
- Adolescents (≥17 yo) & Adults: ≥5 symptoms required.
- Age of Onset: Several symptoms present prior to age 12.
- Pervasiveness: Symptoms must be present in ≥2 settings (e.g., home, school, social settings, work). c
- Duration: Symptoms persistent for ≥6 months.
- Functional Impairment: Clear interference with social, academic, or occupational functioning.
- Symptoms not attributable to another psychiatric disorder (e.g., psychosis, mood disorder, anxiety).
- Symptom Count:
- Assessment Tools:
- Standardized behavioral rating scales (e.g., Vanderbilt, Conners) completed by both parents and teachers to confirm pervasiveness across settings.
Treatment
Options include stimulant and nonstimulant therapy. Stimulant therapy is usually first-line treatment for children ≥ 6 years of age and adults.
Stimulant therapy
- Options: methylphenidate or amphetamine analogues (e.g., lisdexamfetamine, dextroamphetamine)
- Mechanism of action
- ADHD is understood to involve hypoactivity (under-activity) in key brain circuits, particularly the prefrontal cortex, which is responsible for executive functions like attention, impulse control, and planning.
- This dysfunction is linked to insufficient levels or inefficient signaling of the neurotransmitters dopamine (DA) and norepinephrine (NE).
- Adverse effects
- Sympathomimetic effects
- Anxiety, agitation, restlessness, bruxism, tics
- Difficulty falling asleep (insomnia)
- Reduced appetite, nausea, vomiting, weight loss
- Increased arterial blood pressure, tachycardia
- Sympathomimetic effects
Nonstimulant therapy
- Atomoxetine: c2
- MOA: Selective NE Reuptake Inhibitor (SNRI).
- Use: Pts with substance use Hx or tic disorders.
- Key SE: Suicidal ideation (black box warning).
- Alpha-2 Agonists:
- Drugs: Guanfacine, Clonidine.
- Use: Adjunctive, especially for comorbid tics or insomnia; Not very efficient in adult ADHD.
- Key SEs: Sedation, hypotension.
Tip
SSRI is not used since ADHD pathophysiology is primarily linked to dysregulation of dopamine (DA) and norepinephrine (NE)