Summary
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 12th 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.
Epidemiology
- Sex: ♂ > ♀ [1]
- Age of onset: usually before 12 years [2]
- Prevalence: ∼ 5% [1]
Epidemiological data refers to the US, unless otherwise specified.
Etiology
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
Clinical features
- Symptoms of inattention and/or hyperactivity (see “Diagnostics” below)
Diagnostics
| 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
| |
| B |
| |
| C |
| |
| D |
| |
| E |
| |
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).
Differential diagnoses
- Hearing or visual impairment
- Absence seizures
- Thyroid disorders
- Sleep disorders
The differential diagnoses listed here are not exhaustive.
Treatment
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
- ADHD: 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
-
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
- Adverse sympathomimetic effects
- 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.
Prognosis
- 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.