Attention Deficit-Hyperactivity Disorder

Attention deficit-hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in the pediatric population. Based on parental reports, approximately 6.4 million children and teenagers in the United States (11% of children aged 4-17 years) have received a diagnosis of ADHD. The etiology of ADHD is uncertain but appears to be multifactorial and include genetic, environmental, and psychosocial factors. Given its prevalence, all pediatric providers should have an understanding of the diagnosis and management of ADHD. When ADHD impairs a child’s function, medications are generally safe, effective, and tolerable. Data show that medication is particularly effective when paired with behavioral interventions at home and at school.

Diagnosis

The diagnosis of ADHD is clinical and based on history and examination. This diagnosis should be considered for any child aged 4 years or older who presents with symptoms of inattention, hyperactivity, impulsivity, and academic or behavioral difficulties. Although at least some symptoms are required to have been present before the age of 12 years, many individuals with ADHD do not meet full diagnostic criteria until adolescence. Individuals with high cognitive reserve or in highly structured and supportive environments may not experience significant impairment related to their symptoms, and therefore may not present until demands exceed their reserve or the supports in the environment change. Although neurocognitive or neuropsychological testing or behavioral rating scales may be helpful in elucidating symptoms, strengths, and weaknesses of a particular child, no specific tests reliably distinguish between people with ADHD and those without the disorder, and such testing is not required to make the diagnosis.

ADHD Subtypes

The three clinical subtypes of ADHD are based on the presenting symptoms:

• Predominantly inattentive presentation (ADHD-I) meets criterion A1 but not criterion A2.

• Predominantly hyperactive-impulsive presentation (ADHD-HI) meets criterion A2 but not criterion A1.

• Combined presentation (ADHD-C) meets both criterion A1 and criterion A2.

Symptoms in each of these domains have slightly different courses. Children with significant hyperactivity symptoms are likely to present at a younger age, sometimes in preschool. Although overt physical hyperactivity often decreases significantly with age, individuals with ADHD-HI or ADHD-C may still experience significant fidgetiness and restlessness in adolescence and adulthood. Symptoms of inattentiveness typically become more prominent as demands increase in elementary school and often persist into adolescence or adulthood. ADHD overall is more common in boys than in girls, but girls are more likely to present with ADHD-I.

While patients with the different subtypes of ADHD may benefit from the employment of different psychosocial supports or coping mechanisms, the pharmacologic treatments for all ADHD subtypes are the same.

Screening

Multiple standardized assessment tools are available; the National Institute for Children’s Health Quality (NICHQ) Vanderbilt Assessment Scales and Conners Rating Scales are the most widely used. These scales include patient self-assessment (for children old enough to complete) as well as parent and teacher assessments and can be used initially to aid diagnosis and later to monitor treatment efficacy during follow-up.

Neuropsychological Testing

Neuropsychological testing involves a battery of standardized assessments designed to measure psychological functions that are linked to particular brain structures and pathways, including processing speed, attention and concentration, memory, and cognitive ability. This testing is administered by doctorate-level clinicians and requires several hours to complete. Although impairments in attention or concentration can be detected on neuropsychological testing and can aid in diagnostic clarification, the diagnosis of ADHD remains a clinical one. Absence of attention or concentration deficits on neuropsychological testing does not rule out a diagnosis of ADHD. Children do not require neuropsychological testing if history and screening suggest a clear diagnosis of ADHD.

Differential Diagnosis

It is important to consider other conditions that can be mistaken for ADHD or the possibility of comorbid conditions:

• Anxiety: ADHD and anxiety are frequently comorbid conditions; some children require treatment for both. Anxiety on its own can also negatively affect attention.

• Mood disorder: Both depression and mania can impair concentration.

• Learning disability: A child with a learning disability may have difficulty cognitively accessing the material and therefore can appear to have poor concentration or hyperactivity. Neuropsychological testing can be very helpful in this situation.

• Delirium related to acute medical illness: The first sign of delirium is impaired attention (detectable on exam prior to disorientation).

• Psychosis: Patients with schizophrenia or other psychotic illnesses often have impaired attention.

• Substance intoxication or withdrawal: If clinically appropriate, toxicology screens can be useful in clarifying this diagnostic confounder.

• Trauma: Ongoing and historical abuse, neglect, and other adverse childhood experiences can impact attention and impulse control/reactivity. (See the section on Attachment, Trauma, and Other Stressor-Related Disorders in this rotation guide.)

Management

Stimulant medicines are highly effective and are generally considered first-line treatment for impairing ADHD. Nonstimulant medications can be helpful but are less effective than stimulants. Behavioral management and therapy are useful adjunct treatments that can improve outcomes by treating distressing symptoms associated with ADHD, including mood and behavioral issues. In the Multimodal Treatment of Attention Deficit Hyperactivity Disorder (MTA) Study, 579 children (aged 7-9 years) with ADHD were randomly assigned to one of four groups: intensive medication management (once monthly 30-minute visits); intensive behavioral treatment (child-focused treatment, parent training, school interventions); combination treatment (both intensive medication and intensive behavioral treatment); or standard community care (an initial visit and then follow-up at the provider’s discretion). Although all groups showed improvement, children in the intensive medication group and the combination treatment group demonstrated the most improvement. Children in the standard community-care group typically received lower doses of stimulants and did not improve as much as those in the intensive medication-management group. This study highlights the importance of both medication and behavioral management of ADHD, as well as the need to optimize medication dosing. Behavioral interventions, such as cognitive behavioral therapy (CBT) or executive function coaching (specialized instruction around organization, planning, prioritizing, and recognizing when off track) can also be useful interventions. The most efficacious treatment a family is willing to consider should be offered.

Pharmacologic Management

Stimulants

Stimulant medications are safe and effective and the mainstay of treatment for ADHD. The two classes of stimulants are:

• Methylphenidates: The methylphenidates primarily inhibit presynaptic dopamine transporters in the prefrontal cortex and thus increase dopaminergic neurotransmission indirectly.

• Amphetamines: Amphetamines primarily act directly on the dopamine transporter as a pseudosubstrate and increase catecholamine release.

Adverse effects: Some patients tolerate methylphenidates better, some tolerate amphetamines better, and some tolerate either. Common, dose-dependent adverse effects of stimulant medications include insomnia and appetite suppression. Mood lability is not uncommon and can be related either to stimulant doses that are too high or stimulant formulations with overly rapid offset of action. A careful history about timing of symptoms can help distinguish whether mood symptoms are experienced at peak serum levels or as the medication is wearing off.

Medical monitoring: Stimulant medications can increase heart rate (HR) and blood pressure (BP), but these effects are clinically insignificant in most patients (average increase in systolic BP, 3-4 mm Hg; average increase in diastolic BP, 1-2 mm Hg; average increase in HR, 3-4 beats per minute). Prior to initiating a stimulant, patients should be screened for current or congenital cardiac pathology and family history should be reviewed. Screening electrocardiogram (ECG) is not routinely necessary but should be considered in patients with family history of arrhythmia or sudden unexplained death. During treatment with a stimulant, height and weight should be monitored given the potential for decreased appetite and resultant growth effects. Current or prior substance use complicates treatment and might require referral to psychiatry.

Nonstimulant Medication

Nonstimulant medications can be used when stimulants are not tolerated, stimulant therapy alone is not sufficient, or comorbid concerns (anxiety, substance use) warrant a different treatment approach. Nonstimulant medications include:

• alpha-adrenergic agents (clonidine, guanfacine)

• atomoxetine

• viloxazine

• bupropion

Bupropion is not currently approved by the FDA for treatment of ADHD.

Nutritional Supplements

Current evidence suggests that many children with ADHD utilize complementary and alternative medicine (CAM) or dietary interventions, including supplementation and elimination diets. Although these alternatives have not demonstrated as much efficacy as stimulant medication, they are important to be aware of as potential adjuncts and given patient and family preference for such treatment options.

• Polyunsaturated fatty acids (PUFAs) are a well-studied CAM therapy for ADHD.

  • Omega-3 fatty acids are anti-inflammatory, may reduce oxidative stress, and can affect serotonin and dopamine neurotransmission (especially in the frontal cortex). Some evidence suggests the efficacy of omega-3 fatty acid supplementation at a dose of 1-2 grams daily in a formulation with high eicosapentaenoic acid content.

• Melatonin has demonstrated efficacy for sleep-related problems in patients with ADHD (either related or unrelated to stimulant treatment) but not as a treatment for core ADHD symptoms. Notably individuals with ADHD have an increased prevalence of sleep disorders, including delayed sleep phase syndrome, for which melatonin can be effective.

• Vitamin D supplementation as adjunctive therapy to methylphenidate has been linked with small improvements in ADHD symptoms without adverse effects. However, the evidence is too limited to support widespread use.

• No evidence to date supports the use of minerals (iron, zinc) except in the context of deficiencies. Herbal supplements, such as ginkgo biloba and St. John’s wort, have not demonstrated benefit and have the potential for adverse effects.

Prognosis

Recent data suggest that there is significant variability in the longitudinal trajectory of ADHD symptoms. However, it is clear that most (60%-85%) children with ADHD continue to meet criteria for the disorder during adolescence. The data are less clear on adult outcomes. Evidence suggests that many adults continue to have symptoms of ADHD and experience functional impairment in their day-to-day lives, but such symptoms sometimes do not meet full diagnostic criteria for ADHD. This could be secondary to many factors, including change of reporter (parent vs. patient) and compensation for symptoms.

When to Refer

• diagnostic uncertainty

• multiple failed stimulant trials

• patient inability to tolerate stimulants

• comorbidity that increases complexity of management (e.g., substance use)