Attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that presents in childhood with symptoms such as impulsivity, hyperactivity, and inattention. A core feature of this disorder is that symptoms must impair social, occupational, or academic performance. The diagnosis of ADHD may be established at any age, though core symptoms must have been present prior to the patient's 12^th birthday. Management of ADHD is multimodal and typically consists of stimulants (e.g., methylphenidate) in combination with behavioral and school-based interventions. ADHD is associated with adverse long-term consequences including impaired educational and occupational performance and higher rates of substance use and personality disorders.

• Sex: ♂ > ♀ ^[1]
• Age of onset: usually before 12 years ^[2]
• Prevalence: ∼ 5% ^[1]

Epidemiological data refers to the US, unless otherwise specified.

Multifactorial disorder

The general mechanism is hypothesized to be related to an altered catecholamine metabolism.

• Genetic predisposition: family history of ADHD, polymorphisms of the dopamine, serotonin, or glutamate receptor subtypes
• Environmental factors
  • Prematurity, in-utero exposure to alcohol
  • A subset of patients may have symptoms that are susceptible to dietary factors (e.g., food additives, food sensitivities, mineral deficiencies, sugar). ^[3][4]

Comorbidities

• Oppositional defiant disorder
• Conduct disorder
• Learning disabilities
• Depression
• Anxiety disorders

• Symptoms of inattention and/or hyperactivity (see “Diagnostics” below)

Diagnostic criteria (according to the DSM-5) [5]
A	Pattern of inattention and/or hyperactivity that is inconsistent with the developmental level of the individual and lasts for ≥ 6 months Inattention is characterized by ≥ 6 of the following in children or ≥ 5 of the following in adolescents and adults (≥ 17 years of age): Poor attention to details at work/school Difficulty sustaining attention during tasks Does not listen when spoken to directly (e.g., distraction in the absence of an obvious interruption) Inability to complete tasks/instructions at work/school (e.g., easily sidetracked) Struggles to organize tasks/activities (e.g., disorganized work, misses deadlines) Prefers to avoid tasks that require a high amount of mental effort (e.g., homework, preparing reports) Loses things necessary to complete tasks (e.g., stationery, documents) Easily distracted Forgetful (e.g., does not pay bills, does not do homework) Hyperactivity and impulsivity are characterized by ≥ 6 of the following in children or ≥ 5 of the following in adolescents and adults (≥ 17 years of age): Fidgets or squirms in seat Often leaves their seat during inappropriate situations (e.g., during meetings or in class) Restless (runs about in inappropriate situations) Unable to carry out tasks quietly Talks excessively Answers questions prematurely or for others Difficulty waiting their turn (e.g., has problems with lines) Interrupts other people (e.g., in conversation, during activities)
B	Several symptoms are present at < 12 years of age.
C	Symptoms are present in ≥ 2 settings (e.g., school, home, work).
D	Symptoms interfere with important levels of functioning (e.g., school, work).
E	Symptoms are not due to a mental disorder.

Poor school performance in children with ADHD is due to inattention/hyperactivity. Their level of intelligence remains normal and is not directly affected by the disorder.

Establishing the diagnosis of ADHD involves identifying comorbid disorders (e.g., learning disability, psychiatric disorders) as well as ruling out disorders that may mimic ADHD (e.g., hearing or visual impairment, thyroid disorders, sleep disorders).

Behavioral interventions

• Indication: first-line therapy for preschool-aged children and adjunct therapies for school-aged children and adults
• Socio-educational measures
• Behavioral parent training (BPT): teaches parents how to understand and manage their child's condition, how to manage problematic situations, and how to support positive behavior using operant conditioning
• Operant conditioning: an approach in which the desired behavior is modified by positive reinforcement (reward) or negative reinforcement (absence of punishment)

Medication

Stimulants, amphetamine derivates

• Drugs: Methylphenidate, dextroamphetamine, methamphetamine, lisdexamfetamine
• Indication
  • ADHS: first-line therapy for patients ≥ 6 years of age
  • Other indications: narcolepsy, binge eating disorder
• Mechanism of action: indirect and central sympathomimetic activity → increased release and blocked reuptake of norepinephrine and dopamine (minor effect on serotonin) → increased concentration in the synaptic cleft
• Effect
  • Increased mental performance: improved concentration, cognition (learning, remembering, combining), short-term memory, and fine motor skills
  • Reduced potential for conflict
• Side effects
  • Adverse sympathomimetic effects
    • Anxiety, agitation, restlessness, bruxism, tics
    • Difficulties falling asleep (insomnia)
    • Reduced appetite; , nausea, vomiting (causes weight loss)
    • Increased arterial blood pressure, tachycardia
  • Epileptogenic potential: reduces the threshold for seizures and tics
  • Decreased growth rate (reversible if medication is stopped)
  • Euphoria
  • Rarely, priapism
• Dosage: slow titration schedule, as the drug affects each individual differently

Methylphenidate, amphetamines, and amphetamine derivatives are schedule II prescription drugs.

Atomoxetine (nonstimulant)

• Substance class: selective norepinephrine reuptake inhibitor (NRI) that increases the concentration of norepinephrine in the synaptic cleft
• Indications
  • Second-line therapy for patients with ADHD ≥ 6 years of age
  • Preferred in patients with substance abuse disorder or in patients in whom stimulant addiction may be a concern. ^[6]
• Advantage: no potential for addiction → not a schedule II prescription drug (normal prescription drug)
• Limitations: Meta-analyses revealed an increased rate of suicidal actions in children and adolescents being treated with atomoxetine.

Atomoxetine increases the risk of suicidal actions in children and adolescents, therefore, close monitoring (especially at the beginning of the therapy) is indicated.

Other

• Other nonstimulant alternatives with less proven efficacy include clonidine, guanfacine, bupropion, and/or nortriptyline.

• The persistence of symptoms after treatment predicts prognosis into adulthood.
• In 35–65% of patients, symptoms of ADHD and their associated functional impairment will persist into adulthood. ^[7]
• Patients with ADHD are at higher risk of injury (both unintentional and self-injury), substance use disorder, and antisocial personality disorder.