Attention Deficit Hyperactivity Disorder

Pamela Hoffman, M.D.
Emily R. Katz, M.D.

Basic Information

Definition

Attention deficit hyperactivity disorder (ADHD) is a chronic disorder of attention and/or hyperactivity-impulsivity. Symptoms must be present before 12 yr of age, last at least 6 mo, and cause functional impairment in multiple settings. The diagnostic keys for ADHD are described in Table 1.

TABLE1 Diagnostic Keys for Attention Deficit Hyperactivity Disorder

1.
Inattention
1. a.
  
  Careless mistakes in schoolwork, work, or other activities
2. b.
  
  Seems not to listen when spoken to directly
3. c.
  
  Poor follow-through on schoolwork or chores
4. d.
  
  Difficulty organizing
5. e.
  
  Easily distracted by extraneous stimuli and is forgetful

2.
Hyperactivity
1. a.
  
  Trouble sitting still
2. b.
  
  May act as if “driven by a motor”
3. c.
  
  May talk excessively

3.
Impulsivity
1. a.
  
  Trouble holding back in class
2. b.
  
  Trouble taking turns
3. c.
  
  Interrupts

Synonyms

Hyperactivity
Hyperkinetic disorder
Attention deficit disorder (ADD)
ADHD

ICD-10CM CODES
F90.0	Attention-deficit hyperactivity disorder, predominantly inattentive type
F90.1	Attention-deficit hyperactivity disorder, predominantly hyperactive type
F90.2	Attention-deficit hyperactivity disorder, combined type
F90.8	Attention-deficit hyperactivity disorder, other type
F90.9	Attention-deficit hyperactivity disorder, unspecified type
DSM-5 CODES
314.00, 314.01

Epidemiology & Demographics

Peak Incidence

Diagnosis is usually first made in school-aged children (6 to 9 yr).

Prevalence

Five percent to 10% of school-aged children (most prevalent neurodevelopmental disorder among children) and 2% to 5% of adults. Children from families with low socioeconomic status and children with public insurance are diagnosed with ADHD at higher rates than their peers.

Predominant Sex

Among children, male predominance with ratio of 2:1 to 4:1. Among adults, ratio is closer to 1:1 (sex difference may reflect referral bias).

Predominant Age

Some symptoms must occur before age 12 yr. Symptoms (especially motoric hyperactivity) tend to diminish with age. Up to 70% continue to meet criteria in adolescence, and an estimated 40% to 65% have some symptoms in adulthood.

Genetics

Strong polygenetic component. First-degree relatives of ADHD patients have 5 times greater risk of ADHD relative to controls. Studies suggest potential involvement of several genes, including those associated with serotonin and glutamate transporters as well as dopamine metabolism in addition to neuronal development.

Risk Factors

Possible risk factors include in utero tobacco/drug exposure or hypoxia, low birth weight, prematurity, pregnancy, lead exposure (though most children with elevated lead levels do not develop ADHD), head trauma in young children, family dysfunction, low socioeconomic status. Evidence supports possible association between dietary factors (e.g., refined sugar, food additives) and ADHD in a small percentage of patients. A causal link between environmental toxins and ADHD has not been clearly established.

Physical Findings & Clinical Presentation

•
Three types:
1. 1.
  
  Predominantly inattentive: difficulty organizing, planning, remembering, concentrating, starting/completing tasks; symptoms may not be present during preferred activities.
2. 2.
  
  Predominantly hyperactive-impulsive: edgy/restless, talkative, disruptive/intrusive, disinhibited, impatient.
3. 3.
  
  Combined.
•

Usually diagnosed in elementary school when achievement is compromised and behavioral problems are not tolerated. Children with academic underproductivity, problems with peer and family relations, or discipline issues are often referred for evaluation. Of the more than 4 million children in the U.S. who have ADHD, most have comorbid conditions (see the following) and nearly half use special education and mental health services.
•

Up to 50% may have associated disorders such as psychiatric diagnoses (oppositional defiant disorder, conduct disorder, depression, anxiety, eating disorders), learning disabilities, or substance abuse.
•

In adults, motoric hyperactivity is less common, but restlessness, edginess, and difficulty relaxing are often seen. Disorganization and difficulty completing tasks are other common complaints.

Etiology

Strongest evidence exists for genetic inheritance. Other theories include abnormal metabolism of brain catecholamines, structural brain abnormalities, reduced activation in the basal ganglia and anterior frontal lobe, as well as environmental factors (see earlier).

Diagnosis

Differential Diagnosis

•

Medical: visual/hearing impairment, seizure disorder, head injury, sleep disorder, medication interactions, mental retardation intellectual disability, specific learning disorder, autism spectrum disorder/development delay, thyroid abnormalities, lead toxicity, movement disorders.
•

Psychiatric: depression, bipolar disorder, disruptive mood, dysregulation disorder, anxiety, obsessive-compulsive disorder, oppositional defiant disorder, intermittent explosive disorder, conduct disorder, posttraumatic stress disorder, reactive attachment disorder, and substance abuse.
•

Psychosocial: mismatch of learning environment with ability, family dysfunction, abuse/neglect.

Workup

•

Clinical interview should include assessment of symptoms and impact on work/school and relationships; developmental history; personal and family psychiatric history, including substance abuse; social history, including family dysfunction; medical history.
•

Physical examination should be performed to investigate medical causes for symptoms, coexisting conditions, and contraindications to treatment. Special focus should be paid to evaluation of dysmorphic features; neurologic examination, including assessment for neurocutaneous findings; and assessment of hearing and vision.
•

Information from collateral sources (parents, partners, teachers) is crucial to diagnosis. Many patients will not display symptoms during an office visit and may underreport or overreport symptoms.
•

Self-rating scales and standardized symptom-specific questionnaires from collateral sources can help diagnose and assess response to treatment. The use of ADHD-specific rating scales over broadband behavioral scale is associated with improved sensitivity and specificity.
•

Laboratory or imaging studies should be undertaken only if indicated by history or physical examination.
•

The FDA has approved a quantitative EEG test to aid in the diagnosis of ADHD in children, but sufficient evidence to support its routine use is lacking.
•

Ancillary testing (e.g., IQ/achievement testing, language evaluation, and mental health assessment) may be indicated based on clinical findings and may require referral.

Treatment

Nonpharmacologic Therapy

•

The majority of studies comparing the efficacy of pharmacologic vs nonpharmacologic interventions demonstrate the superiority of pharmacologic treatments.
•

Studies on combined treatments have not shown significant improvements in core ADHD symptoms when behavioral treatments are added to stimulant medications. However, improvements in related areas of concern such as parent-child relations, aggressiveness, teacher-rated social skills, and reaching achievement have been seen in combined treatment groups.
•

Prevailing opinion favors a multimodal approach in which nonpharmacologic behavioral therapies including parent-child behavioral therapy and social skills training can be used to target comorbid conditions or behaviors that have not responded to medication.
•

Behavioral therapy alone is often considered when children are under 6 yr, symptoms and impairment are mild, if parents are opposed to or patients cannot tolerate medications, or if there is uncertainty or disagreement about the diagnosis (e.g., between parents and teachers).
•

Educational interventions are recommended, particularly in the setting of learning disabilities. Children with ADHD are entitled to reasonable educational accommodations under a 504 Plan or the Individuals with Disabilities Education Act.
•

Behavioral interventions (e.g., goal setting and rewards systems) show short-term efficacy and are endorsed by most national organizations (e.g., American Academy of Pediatrics, American Medical Association). Time management and organizational skills appear useful. Social skills training may also be useful.
•

Psychotherapy such as cognitive therapy, play therapy, or insight-oriented therapy are unlikely to be useful in addressing the core symptoms of ADHD. However, it may be beneficial in treating comorbid psychiatric conditions.
•

Preliminary research concentrating on improving diagnosis, treatment outcomes, and medication compliance using eHealth (telemedicine, mobile apps, text reminders) have been promising.
•

Elimination diets are not routinely recommended.
•

Many support and advocacy groups provide education and other resources (e.g., Children and Adolescents with ADHD, National ADD Association, American Academy of Child and Adolescent Psychiatry).

Acute General Rx

•

Most studies on treatment of ADHD are performed in children; limited data available on adults.
•

Mainstay of treatment is stimulant medications. Second-line therapies include antidepressants and alpha-agonists.
•
Stimulants:
1. 1.
  
  Release or block uptake of dopamine and norepinephrine.
2. 2.
  
  Include short- and long-acting methylphenidate, dextroamphetamine, and dextroamphetamine/amphetamine combinations (mixed amphetamine salts). A methylphenidate patch (Daytrana) is available, as is a pro-drug form of dextroamphetamine, lisdexamfetamine (Vyvanse), which is designed to limit the abuse potential. A long-acting oral suspension of methylphenidate (Quillivant XR), a long-acting chewable tablet of methylphenidate (QuilliChew ER), a long-acting orally disintegrating tablet of mixed amphetamine preparation (Adzenys XR-ODT) and a long-acting liquid amphetamine preparation (Dyanavel XR) are now available.
3. 3.
  
  All stimulants equally effective; however, not all patients improve with stimulants. Patients who do not respond well to one stimulant may respond to another.
4. 4.
  
  Do not cause euphoria or lead to addiction when taken as directed.
5. 5.
  
  Improve cognition, inattention, impulsiveness/hyperactivity, and driving skills. Limited impact on academic performance, learning, and emotional problems.
6. 6.
  
  Side effects are usually mild, reversible, and dose dependent, including anorexia, weight loss, sleep disturbances, increased heart rate and blood pressure, irritability, moodiness, headache, onset or worsening of motor tics, reduction of growth velocity (but not adult height). Do not worsen seizures in patients on adequate anticonvulsant therapy. Rebound of symptoms can occur with withdrawal of medication.
7. 7.
  
  Stimulants have generally been associated with cardiovascular events and death. Patients should be carefully evaluated for cardiovascular disease before beginning therapy and be periodically monitored, including blood pressure checks, while they are treated. However, despite concerns regarding cardiovascular risk, these medications are generally safe. Recent studies have shown that among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, is not associated with an increased risk of serious cardiovascular events. Routine, pre-treatment screening with ECGs is not currently recommended by the American Academy of Pediatrics or the American Academy of Child and Adolescent Psychiatry.
•
Atomoxetine (Strattera):
1. 1.
  
  Selective norepinephrine reuptake inhibitor.
2. 2.
  
  Generally felt to be less effective than stimulants, but a useful alternative in patients who have not tolerated or responded to stimulants or in the setting of patient or family substance abuse.
3. 3.
  
  Efficacy and safety of use beyond 2 years of treatment have not been studied. There have been reports of behavioral abnormalities and increased suicidality in children and adolescents.
4. 4.
  
  Side effects: gastrointestinal upset, sleep disturbance, decreased appetite, dizziness, sexual side effects in men. Cardiovascular side effects have also been reported.
5. 5.
  
  There have been rare reports of severe liver injury in adults and children.
•
Antidepressants (bupropion, imipramine, desipramine, nortriptyline):
1. 1.
  
  May be useful in patients with coexisting psychiatric disorders.
2. 2.
  
  Studies comparing efficacy versus stimulants are inconclusive.
3. 3.
  
  Side effects: arrhythmias, anticholinergic effects, lowering of seizure threshold.
•
Alpha-2-adrenergic agonists (clonidine, guanfacine):
1. 1.
  
  Appear to be less effective than stimulants, but may be particularly useful as an adjunctive treatment to stimulants, particularly in patients with a partial stimulant response or who experience side effects such as sleep disturbance or concurrent symptoms of overarousal, irritability, or aggression.
2. 2.
  
  Extended-release formulations of guanfacine (Intuniv) and clonidine (Kapvay) have been approved by the FDA for treatment of ADHD in children ages 6 to 17 yr. A transdermal clonidine patch is also available.
3. 3.
  
  Potential side effects include sedation, fatigue, headache, bradycardia, hypotension, and depression.
•

Use of medications, particularly stimulants (which are monitored under the Controlled Substance Act), requires frequent monitoring.

Disposition

•

Although symptoms may change over time, for many patients ADHD represents a chronic condition that requires lifelong management.
•

Patients are at higher risk for academic underachievement, lower socioeconomic status, work and relationship difficulties, high-risk behavior, and psychiatric comorbidities.

Referral

•

Diagnosis complicated by difficult-to-treat comorbid psychiatric conditions, developmental disorders, or mental retardation
•

Lack of adequate response to stimulants/atomoxetine/alpha-adrenergic agents

Pearls & Considerations

•

The World Health Organization’s Adult Self-Report Scale (ASRS) v1.1 has good sensitivity and adaptability to the primary care setting.
•

Among adults with persistent ADHD symptoms treated with medication, trials have shown that the use of cognitive behavioral therapy compared with relaxation with educational support resulted in improved ADHD symptoms, which were maintained at 12 mo.
•

ADHD has been associated with criminal behavior in some studies. Data analysis has shown that among patients with ADHD, rates of criminality are lower during periods when they receive ADHD medication.
•

Recommendations for the diagnosis and management of ADHD have been published by the Centers for Disease Control and Prevention (www.cdc.gov/ncbddd/adhd/treatment/treatment.html).

Ferri – Attention Deficit Hyperactivity Disorder