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.
- Patients generally have normal intelligence, but school/work performance is impaired due to symptoms.
Diagnostics
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:
- 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.
- Key SEs: Sedation, hypotension.
Tip
SSRI is not used since ADHD pathophysiology is primarily linked to dysregulation of dopamine (DA) and norepinephrine (NE)