Chapter 9. Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is one of the most frequently encountered disorders in pediatric and adolescent medical practice. ADHD is a complex developmental disorder of brain and behavior that makes its initial appearance in preschool ages, persists into adolescence, and, in some individuals, into adult life.1 In 2007, the CDC summary of health statistics for U.S. children indicated that 4.5 million children (7%) between the ages of 3 and 17 years had been diagnosed with ADHD. The rate for boys (11%) was twice the rate for girls (4%).2 While the degree of persistence of this disorder into adulthood is still unclear, estimates from longitudinal studies suggest between 1% and 6% of the adult population has symptoms of ADHD.3

Historically, symptoms of impulsivity, hyperactivity, and inattention were first attributed by Still (1902) to neurological disorder. Therefore, early clinical diagnosis were based upon presumptive "organic" etiological factors such as brain trauma, encephalitis, or other brain conditions that resulted in problems of attention, impulse control, emotional disregulation, and cognition. Gradually, however, the clinical diagnostic emphasis shifted to what Shelton4 labeled "symptom-based" description of the disorder, which preceded current classification systems such as the American Psychiatric Association's DSM-IV. In 2000, the empirically updated DSM-IV-TR5 was published and provides the current diagnostic criteria and ICD-9 codes for several subtypes of ADHD. These include (1) Attention-Deficit/Hyperactivity Disorder, Combined Type (314.01); (2) Attention-Deficit/ Hyperactivity Disorder, Predominantly Inattentive Type (314.00); (3) Attention-Deficit/Hyperactivity Disorder, Predominantly Hyperactive–Impulsive Type (314.01); and (4) Attention-Deficit/Hyperactivity Disorder, Not Otherwise Specified (314.9). While the first three subtypes are differentiated from each other on the basis of predominant clinical presentation, the fourth subtype is reserved for those patients who, despite the presence of prominent symptoms of inattention or hyperactivity– impulsivity, do not meet full diagnostic criteria for a specific ADHD subtype. Similarly, for adolescents and/or adults who currently have symptoms but no longer meet full criteria, the label "In Partial Remission" would be added to the diagnostic code (eg, 314.01—In Partial Remission). Table 9-1 presents the common signs and symptoms described for diagnostic purposes under the three primary domains of inattention, hyperactivity, and impulsivity.

Current diagnostic criteria for any of the three ADHD subtypes noted above include

1. Six or more of the symptoms of inattention and six or more of the symptoms of hyperactivity– impulsivity must be present.

2. Symptoms must have been present for 6 or more months prior to diagnosis.

3. Some symptoms that have caused impairment must be present before age 7 years.

4. Symptoms causing some impairment must be present in two or more settings.

5. There must be clear evidence of clinically significant impairment in social, academic, or occupational functioning.

6. These symptoms do not occur exclusively during the course of another disorder, such as pervasive developmental disorder and are not better accounted for by another disorder.

There has been considerable controversy about the current diagnostic criteria,6 primarily focused on the age differences in presentation, gender differences in diagnosis, longitudinal course,7,8 and impact of comorbid behavioral, emotional, and cognitive disorders accompanying ADHD.9 What is not controversial is the need for careful, systematic diagnostic approaches to this very complex developmental disorder, and for continued refinement in our understanding of the disorder and its treatment.

A number of different causes of the brain dysfunctions that result in ADHD have been examined in the search for the etiology of this disorder. Among these are (1) differences in brain morphology and development, (2) differences in neurotransmitter activity, (3) differences in neuroelectrophysiology, (4) differences in genetics, and (5) interactions of genetic risk and environmental factors. Structural differences in the brains of children and adults with ADHD compared to normal control have included anterior and posterior regions of the corpus callosum, basal ganglia and related frontal-striatal structures, caudate nucleus, and prefrontal versus occipital volumes.10,11 Whether smaller volumes in these anatomic sites for ADHD result in the symptoms assumes that smaller size equates to less functional capabilities. However, there appears to be some support for the importance of prefrontal-striatal systems in development of behavioral response inhibition. More recently, longitudinal imaging studies have also supported the role of delayed maturation of superior and dorsolateral prefrontal cortex and in the middle and superior temporal cortex in children diagnosed with ADHD.12

Studies have employed functional neuroimaging techniques in order to assess for differences in brain activity in selected structures of the brains of children and adults with ADHD. Studies of dorsolateral prefrontal cortex and ventrolateral prefrontal cortex, dorsal anterior cingulate cortex, and striatum predominate because these anatomic areas have been implicated in functions such as vigilance, selective and divided attention behavioral inhibition, and aspects of executive functioning including planning, response selection, and response initiation. Support for hypofunction in dorsal anterior and posterior cingulate cortex has been demonstrated in a number of recent FMRI studies.13 Earlier PET and SPECT studies of ADHD subjects, although methodologically flawed due to lack of control groups, found increased regional cerebral blood flow in dorsolateral prefrontal cortex, caudate, and thalamus when methylphenidate was administered.13

Neuroelectrophysiological studies utilizing quantitative EEG (QEEG) and event-related potentials (ERPs), while problematic compared to MRI in terms of spatial resolution, have also been utilized to study brain functioning in ADHD subjects compared to controls. Results, however, have not yet enabled these two methodologies to explicitly address the specific anatomic substrates involved in the problems of inattention, impulsivity, and executive control functions in ADHD subjects. Genetic studies have focused upon the familial pedigree of individuals diagnosed with ADHD. Current views suggest that ADHD results from polygenetic rather than a single gene mode of inheritance with approximately 70% to 95% variance in symptoms. Concordance rates for identical twins are considerably higher compared to concordance rates in fraternal twins (70%-80% vs. 30%-40%). Specific dopamine receptor genes identified include DRD2 and DRD5, the dopamine transport gene DAT1, and potentially defective alleles of the dopamine beta hydroxylase enzyme (DBH) that is important in the dopamine-to-norepinepherine conversion.14 Recently, a large-scale assessment of 51 candidate genes in pathways related to dopamine, norepinepherine, and serotonin supported earlier reports of the role of DRD4 and DAT genes in the ADHD phenotype as well as 16 other potential genes, lending further support for the polygenetic model of ADHD.

A final group of studies have focused upon environmental factors, genetic profiles, and specific subtypes of ADHD. Previously, a number of acquired risk factors for the development of ADHD have been identified. These include pregnancy and birth complications, low birth weight, traumatic brain injury, prenatal substance exposure, and lead exposure. However, these factors likely carry less influence in the likelihood of developing ADHD, or at least are responsible for fewer cases, than genetic factors. Recently, Swanson and associates15 presented a potential model that addresses gene–environment interactions that may affect fetal adaptations in development of dopamine neurons and contribute to development of different subtypes of ADHD. The authors critically review the research literature that provides support for the dopamine deficit theory underlying ADHD, and suggests future studies, in particular those needed to address the emergence of the ADHD phenotype over time.

The clinical presentation of ADHD varies by age. Children from age 3 years through the adolescent years and even adults can present with symptoms of overactivity, inattention, and impulsivity. Parents of children 7 years or younger may report the presence of overactivity, impulsivity leading to sometimes risky behavior, sleep disorders (eg, difficulty falling asleep, disruptive sleep, and early morning awakening), short attention spans, and inability to sustain focused attention. Some of these behavioral problems may have been noticed in the preschool years but emerged as clearly problematic upon entry to prekindergarten or kindergarten classes. Once in the school environment, teacher reports are also included in the presentation. Typical teacher reports focus on problems such as failure to follow classroom rules, frequent out-of-seat behavior, difficulty completing assigned work, interrupting others, easily distracted, distracting other students trying to do classroom activities, failure to turn in assignments, and less frequently, aggression towards other students or arguing with others.

During the primary grades, problems in academic functioning and achievement may lead to questions regarding a learning disability in reading, mathematics, or spelling/writing. While research has suggested that both boys and girls may exhibit some or all of these behavioral problems, a subset of children (more commonly girls than boys) present with parental and school complaints of failure to complete assigned school work, inattentive (sometimes "spacey") behaviors, slowness in initiating or completing assignments, and disorderly school papers and work habits.

In general, most research has reported that primary symptoms of hyperactivity may diminish during adolescence and into adult years. However, continuing problems in short attention span, difficulties with sustained attention and distractibility, inattention to detail, problems meeting deadlines, and excessive daydreaming have been reported. For some adolescents and adults, impulsivity remains a problem that can lead to poor decision making and risk-taking behaviors. Employment and/or educational/vocational underachievement may lead to depressive and anxiety complaints. Higher rates of alcohol and substance abuse, marital discord, and legal problems have been described in some longitudinal studies of childhood ADHD.16,17

History and Examination

In 2007, the American Academy of Child and Adolescent Psychiatry issued practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder.18 The report was an update of an earlier set of guidelines published in 1997 and complements the guideline issued by the American Academy of Pediatrics in 2000.19 The following recommendations were made:

1. Screening for ADHD should be part of every patient's mental health assessment. Screening should specifically ask questions regarding presence of the major symptoms of ADHD (inattention, hyperactivity, and impulsivity) and whether these symptoms cause impairment. If the parent reports any symptoms or if the patient scores in the clinical range for ADHD symptoms, then a full evaluation is indicated.

2. Evaluation for ADHD should consist of clinical interview with patient and parent, obtaining information about the patient's school or day care functioning, review of patient's medical, social, and family history, and evaluation for comorbid psychiatric disorders.

3. Additional neuropsychological and neurological studies, including EEG, MRI, SPECT, or PET scanning, are not indicated for the diagnosis of ADHD in the presence of an unremarkable medical history.

4. Psychological and neuropsychological tests should be performed if the patient's history suggests low general cognitive ability or low achievement in language or mathematics relative to the patient's intellectual ability. Additional neuropsychological, speech and language assessments, and computerized testing of attention or inhibitory control may be indicated by the findings of standard psychological assessment.

5. The clinician must evaluate the patient with ADHD for the presence of comorbid psychiatric disorders. If the patient meets full DSM-IV criteria for a second disorder, then the clinician should develop a treatment plan to address each comorbid disorder in addition to ADHD.

6. A well thought-out and comprehensive treatment plan should be developed for the patient with ADHD.

7. The initial psychopharmacological treatment of ADHD should be a trial with an agent approved by the FDA for the treatment of ADHD (eg, dextroamphetamine, D- and DL-methyl-phenidate mixed salts amphetamine, and ato-moxetine).

8. If none of the above agents result in satisfactory treatment, the clinician should undertake a careful review of the diagnosis and then consider behavior therapy and/or the use of medications not approved by the FDA for treatment of ADHD.

9. During a psychopharmacological intervention for ADHD, the patient should be monitored for treatment-emergent side effects.

10. If a patient with ADHD has a robust response to psychopharmacological treatment and subsequently shows normative functioning in academic, family, and social functioning, then psychopharmacological treatment of ADHD alone is satisfactory.

11. If a patient with ADHD has a less than optimal response to medication, has a comorbid disorder, or experiences stressors in family life, then psychosocial treatment in conjunction with medication treatment is often beneficial.

12. Patients should be assessed periodically to determine whether there is continued need for treatment or if symptoms have remitted, treatment of ADHD should continue as long as symptoms remain present and cause impairment.

13. Patients treated with medication for ADHD should have their height and weight monitored throughout treatment.

Figure 9-1 presents a schematic of the diagnostic and intervention steps recommended by the AACAP.

Differential Diagnosis

As noted earlier, there are three subtypes of ADHD that have formal criteria for diagnoses in DSM-IV-TR (Attention-Deficit/Hyperactivity Disorder, Combined Type; Attention- Deficit/Hyperactivity Disorder, Predominantly Inattentive Type; and Attention-Deficit/hyperactivity Disorder, Predominantly Hyperactive–Impulsive Type). This listing of a total of 15 symptoms across the 3 domains of Inattention, Hyperactivity, and Impulsivity cannot occur exclusively during the course of a Pervasive Developmental Disorder, Schizophrenia, or other psychiatric disorders, and is not better accounted for by another mental disorder such as Mood Disorder, Anxiety Disorder, Dissociative Disorder, or Personality Disorder.

ADHD should also be distinguished from a number of medical disorders that can produce some of the symptoms, including sensory impairments (hearing and vision), brain injury, developmental language disorders, inborn errors of metabolism, renal insufficiency, endocrine deficiencies, lead toxicity, asthma, seizure disorders, progressive neurological disorders, and malnutrition.

Environmental factors that could lead to ADHD symptomatology include poor learning environment, curriculum not suited to the child, dysfunctional home environment, poor parenting, neglect or abuse, and parental psychopathology.

Comorbid psychiatric and developmental disorders that must also be identified and/or ruled out include specific learning disabilities, oppositional defiant disorder (ODD), conduct disorder (CD), developmental delay, anxiety disorder, obsessive-compulsive disorder (OCD), depressive disorders, and posttraumatic stress disorder. There is a fairly high incidence of four comorbid disorders in patients diagnosed with ADHD. These include Oppositional Defiant Disorder/Conduct Disorder (30%-50%), anxiety disorder (23%-30%), and depressive disorders (15%-38%). In addition, an estimated 20% to 25% of children with ADHD have a diagnosed learning disability as well. There is also an increased incidence of tic disorders among children diagnosed with ADHD (10%-15%). Table 9-2 presents the most frequent comorbid disorders among children and adolescents diagnosed with ADHD.

Diagnostic Tests

A recent review by Rapport and colleagues20 supported the assertion that there is no one test that, used alone, can diagnose ADHD. However, a number of different behavioral interviews, checklists, and rating scales for the diagnosis have been developed to assist the clinician who is evaluating a patient for ADHD. These include diagnostic interviews such as the Diagnostic Interview Schedule for Children–IV (DISC-IV)21 and the Diagnostic Interview for Children and Adolescents–IV (DICA-IV),22 which are based upon the DSM-IV diagnostic criteria. Behavioral checklists can be divided into two types: (1) broadband and (2) narrow band based upon the comprehensive sampling of problem behaviors. Broadband parent rating scales are often used in which parents rate a variety of problematic behaviors on Likert-type scales. Examples of these types of instruments include the Behavioral Assessment Rating System for Children–2 (BASC-2),23 the Child Behavior Checklist (CBCL)–Parent Report Form,24 and the Conners Rating Scales–3.25 Narrow band rating scales and checklists include the Brown Attention-Deficit Disorder Scale (BADDS)26 and the Swanson, Nolan, and Pelham Rating Scale (SNAP-IV).27 Teacher rating scales are often available in parallel to both broadband and narrow band rating scales to allow for determination of problematic behaviors in school settings. These enable the clinician to evaluate for the requirement of symptoms in two or more settings. There are other psychological instruments available that assess for mood disorders, such as the Child Depression Inventory (CDI)28 or the Revised Children's Manifest Anxiety Scale (RCMAS).29 Finally, the clinician may obtain report cards from school and results from standardized achievement tests that allow for determination of problems in academic classroom performance and achievement, consistent with potential comorbid learning disabilities.

Pharmacological treatment for the core symptoms of ADHD is typically the first-line intervention approach to this behavioral disorder.18 As recommended by the American Academy of Child and Adolescent Psychiatry (AACAP), the patient's treatment plan, once developed, may consist of pharmacological and behavior therapy. If a drug therapy approach is taken, the physician must review both effective therapies and the family's preferences for treatment approaches. Medications to be employed can be broadly categorized into "first-line," "second-line," and other types according to their FDA approval guidelines and those of the AACAP. Second-line and other medications, such as antipsychotics, have been used by some physicians to treat comorbid disorders or severe behavioral problems arising in the course of treatment for ADHD.

Table 9-3 presents a listing of medications that have been utilized in treating ADHD. The physician should follow guidelines regarding any required tests prior to initiating drug therapy (eg, EKG). Once drug therapy is initiated, the physician should monitor response to the type and dosage of the medication as well as any apparent side effects. For many practitioners, this requires more frequent visits during the initiation of drug treatment. Once the efficacy of the drug therapy is established for the patient, less frequent follow-up visits are needed.

Despite the prevalence of pharmacological interventions, many of the social, family, and academic problems experienced by the patient may not be alleviated without additional interventions. A variety of therapies are available that address the problems attendant to a history of ADHD symptomatology. These include individual behavior therapy, social skills training, family therapies, and combinations of these treatments. The recent guidelines of the AACAP, however, suggest that research on these additional interventions suggests their results show only a relatively minor impact on the course of treatment. Equally important is the need for psychoeducational interventions. For the child or adolescent with a diagnosed learning disability, an individualized educational plan (IEP) utilizing exceptional student education (ESE) resources is required by federal ADA legislation. For the child with academic deficiencies who does not meet criteria for the diagnosis of a learning disability, an IEP should still be developed under the 504 plan that may include modifications in classroom seating, weekly reports to parents, and academic support for identified areas of academic deficiencies. Most recently, school districts must also operationalize the specifics of any remediation plan and formally assess the child's response to the intervention (RTI).

A final concern to parents is the length of treatment. While clearly ADHD has been described as a chronic disorder with differing expression of symptoms (phenotype) with increasing age, the AACAP notes that the lack of large-scale longitudinal research in this disorder makes decisions regarding treatment "holidays" and duration difficult. For these, collaboration between physician and patient is critical to effective management of the child's care through his or her development. In particular, comorbid problems may emerge during adolescence, after high school matriculation, and extend into adult life.9,30