Multiple neuroimaging studies have documented consistent abnormalities in brain
structure and development with youth and adults with ADHD. Subjects with ADHD
have been shown to have reductions in global brain volume.
reduction in volume is most prominent in the prefrontal cortex, basal ganglia,
cerebellum, and parieto-temporal regions.
24 Functional magnetic resonance imaging
studies have also shown hypoperfusion with memory tests in the anterior cingulate
25 This area of the brain is responsible for behavioral and
functional abilities that may manifest in patients with ADHD as difficulties in
organization, mood, motivation, self-regulation, and ability to retain specific
information while performing a particular task, which are abilities referred to as
executive functioning. These findings are research population–based findings. These
studies are not yet useful in clinical practice for accurate diagnosis.
ADHD is a heterogeneous behavioral disorder with a variety of theorized etiologies.
Clearly, the research suggests a strong genetic component. However, to this point, no
specific genetic risk factor has been identified.
20 As a result, other environmental and
congenital etiologies have been considered and studied. Examples of studied
etiologies for ADHD include maternal smoking, dietary factors, prematurity/low
birth weight, and family environment/parenting behavior. Of these proposed factors,
low birth rate is the factor with the most confirming research evidence.
potential impact of parenting behavior, in particular, is a complex question as youth
with ADHD often present more significant challenges to parents. Further, as ADHD
is highly heritable, many parents of youth with ADHD may have ADHD themselves.
DIAGNOSIS, SIGNS, AND SYMPTOMS
The diagnosis of ADHD is a clinical diagnosis that may be supported by various
types of screening tools and neuropsychologic assessment. The diagnosis of ADHD
in a child is based upon the DSM-5 criteria (Table 89-1). The evaluation should
include clinical interviews with the patient and/or parent, physical examination
(including neurologic status), obtaining history regarding functional pattern in school
or daycare setting, evaluation for comorbid psychiatric disorders, and review of the
patient’s medical, social and family histories.
2 Other sources of valuable information
include performance reports (e.g., report cards or job reviews) and ADHD rating
scales scored in two different settings.
4 There are a number of validated rating scales
available both proprietarily and in the public domain. Some of the rating scales have
different versions for parents and teachers. Rating scales are helpful both for
diagnosis and for monitoring treatment outcome.
The recent publication of DSM-5 included a number of revisions to the diagnostic
criteria for ADHD. To meet criteria for ADHD, the child must have six or more
symptoms present in two different settings (e.g., home, school, etc.) for a minimum of
6 months. Furthermore, there must be evidence that these symptoms were present
before the age of 12 years. Based on these criteria, three types of ADHD are
identified: predominantly inattentive, predominately hyperactive/impulsive, and
combined. The diagnostic criteria require that the symptoms interfere with or impact
functioning in daily life so that care providers will look for symptoms that have a
negative impact on the child’s education, relationships, or social life (see Table 89-
1). On occasion, however, parents or teachers may “pressure” clinicians into writing
psychostimulant prescriptions for a “let’s see if it helps” trial. If the medication is
helpful, they may assume incorrectly that the diagnosis of ADHD is validated.
Additionally, DSM-5 eliminated the exclusion criteria for Autism Spectrum
Disorder. However, the DSM-5 mandates that the symptoms of ADHD “do not occur
exclusively during the course” of another psychiatric disorder.
Diagnostic Criteria for Attention Deficit Hyperactivity Disorder
home, school, or physician’s office.)
Careless mistakes or inattention to detail
Cannot follow instructions and does not complete tasks
Difficulty organizing tasks and activities
Avoids and/or dislikes chores or homework
Loses things needed for tasks and activities
Easily distracted by extraneous stimuli
Hyperactivity/Impulsivity Factor
home, school, or physician’s office.)
Fidgets with hands/feet or squirms in chair
Cannot remain seated in the classroom
Uncontrollable/inappropriate restlessness
Difficulty in engaging in play or leisure activities quietly
Often on the go and appearing driven by a motor
Blurts out answer prior to completion of question
Interrupts or intrudes on others
Establishing a diagnosis of ADHD in an adult who has never been treated for the
disorder during childhood is difficult. In adults, ADHD is a clinical diagnosis that
relies on their recollection of ADHD symptoms as a child to which DSM-5 criteria
validated for children are applied. Unlike teachers who are ordinarily familiar with
the symptoms associated with ADHD in children, spouses, coworkers, and
employers are often unfamiliar with ADHD as a disorder that can also affect adults.
They may attribute the individual’s difficulties to being lazy or to underachievement.
Between the ages of 10 and 25 years, the signs and symptoms of ADHD decrease in
frequency and severity by about 50% every 5 years but will generally persist into
In the differential diagnosis of ADHD, it is critically important to
distinguish ADHD from various behavioral, developmental, or medical conditions.
Psychiatric comorbidity is more common with ADHD as up to 87% of children will
be diagnosed with at least one additional psychiatric disorder and 67% have at least
Other psychiatric conditions that frequently coexist or imitate symptoms of ADHD
include conduct disorder, oppositional defiant disorder, Tourette syndrome,
depression, anxiety disorders, and obsessive–compulsive disorder. Of these
conditions, anxiety disorders and mood disorders are most commonly misdiagnosed
as ADHD. The comorbidity of ADHD and learning disabilities is both complex and
often leads to significant academic challenges. Studies suggest that 25% to 35% of
youth with ADHD will also have language-based or other learning disabilities.
Clinical wisdom suggests that ADHD often presents early in the child’s academic
career (e.g., kindergarten or first grade), whereas learning disabilities may present
later in the elementary years, when children are “reading to learn” rather than
“learning to read.” Medication is a central treatment component for ADHD, whereas
learning support and specialized teaching strategies are the interventions of choice
for youth with learning disabilities. Medications are not helpful for the treatment of
It has been known for decades that family histories from first-degree relatives of
probands with ADHD reveal increased rates of ADHD (25% concordance rate),
polysubstance dependence, antisocial personality disorder, depression, and anxiety
28 Children with ADHD are at an increased risk of having antisocial
behavior, depression, and substance abuse problems as adults. ADHD symptoms
persist into adulthood in the majority of these comorbid patients.
ADHD are usually self-sufficient, but they have poorer academic performance,
poorer job performance, and lower socioeconomic status than do their siblings. They
also have more frequent divorces, job changes, and car accidents. Most adults with
ADHD report a high level of subjective distress (79%) and interpersonal problems
Medical conditions often complicate the diagnosis of ADHD and should be
excluded before initiating treatment. These medical conditions include head injuries,
seizure disorders, metabolic disorders, cerebral infection, toxic exposures (e.g.,
chronic lead exposure), sleep problems, substance abuse, and hyperthyroidism.
QUESTION 1: M.T. is a 12-year-old girl who recently started middle school. M.T.’s mother calls the
you think about the differential diagnosis?
Depression is the most prominent diagnosis that comes to mind. However, it is
important to remember that comorbidity is quite common in youth with psychiatric
disorders. It is important to consider if there are underlying, less obvious disorders
or circumstances that may be contributing.
CASE 89-1, QUESTION 2: What are the next steps in the evaluation?
The pediatrician refers M.T. to a child/adolescent psychiatrist for evaluation. The
professionals help the parents request an educational assessment through the school.
The latter includes both an academic and psychologic assessments. The assessments
suggest underlying poor self-esteem. However, there is also evidence of slow
processing speed and other evidence of ADHD and executive functioning deficits.
The Vanderbilt rating scales confirm the diagnosis of ADHD.
There are a number of validated instruments to assist with the diagnosis and
clinical management of ADHD. Often, these instruments have a parent and teacher
version. Commonly used instruments include the Conners Global Index, the SNAP
IV, DuPaul Rating Scale for ADHD, and the Vanderbilt Rating Scale. Some rating
scales are proprietary and others such as the Vanderbilt is in the public domain.
CASE 89-1, QUESTION 3: What are the first-line interventions?
The psychiatrist provides psychoeducation to M.T. and her parents about ADHD.
They discuss that ADHD may be missed more commonly in girls, and that youth with
ADHD often develop concurrent depression, anxiety, conduct disorders, and
substance-use disorders because their experience in school and activities often leads
to feelings of inadequacy. Additionally, an Individualized Educational Plan (IEP) is
developed for M.T. to provide more supports in the school setting. Special
accommodations such as added time for exams, a seat in the front of the class, and the
availability of fidget toys are specified in the IEP.
M.T. continues in counseling with the social worker, in which they focus on
cognitive and behavioral strategies to manage both her ADHD symptoms and her
depression and poor self-esteem. All agree that it is prudent to hold off on any
medication for depression to see if the other interventions are effective in alleviating
The ADHD symptoms are tracked with Vanderbilt rating scales completed by
parents and teachers. Medication treatments for ADHD are discussed. With informed
consent, a trial of a psychostimulant is begun.
Optimal strategies to manage ADHD symptoms that are moderate to severe in nature
should focus on the combined use of behavioral and pharmacotherapy interventions.
It is important to recognize that ADHD is a chronic disorder with symptoms that
frequently continue into adolescence and adulthood. Before developing a treatment
plan, defined and realistic treatment goals should be established collaboratively with
the child, parent, and school.
Several ADHD consensus statements, practice parameters, and guidelines have
been developed, based on both evidence-based literature evaluation and expert
opinions, to assist clinicians in evaluating, diagnosing, and managing patients with
During the years, numerous psychosocial or educational programs have been studied
for their potential benefit in controlling ADHD symptoms and maximizing function.
Behavioral interventions have been among the most popular nonpharmacologic
approaches, with programs emphasizing the creation of a structured environment
containing minimal distractions both at home and in school. Contingency training is
another common component of behavioral therapy for ADHD, with children
receiving tokens for specific tasks or achievements, as well as punishments (e.g.,
revoking privileges) for maladaptive behaviors. Although most treatment guidelines
continue to advocate trying some type of structured behavioral modification, the
empiric evidence that such programs improve functioning or prognosis is certainly
not as strong as it is for pharmacotherapy.
The previously mentioned Multimodal Treatment Study of Children with ADHD
was a landmark study in reviewing the relative impact of medication and
14 The MTA Cooperative Group study, as it is commonly
known, was designed to compare long-term medication and behavioral treatments
with respect to efficacy and acceptability. A group of 579 children between 7 and 10
years of age with the combined type of ADHD were recruited and randomly assigned
to four different treatment groups: medication management, behavioral treatment,
medication plus behavioral treatment, or typical community treatment. Behavioral
interventions were delivered in a group-based recreational setting and included an 8-
week, 5-days/week, 9-hours/day, intensive program administered by a counselor or
aide. Once school started, the subjects in this arm of the study received 60 school
days of a part-time, behaviorally trained, paraprofessional aide who worked directly
with the child. In addition, the child’s teacher received 10 to 16 sessions of biweekly
consultation that focused on classroom behavior management strategies. Daily
behavior report cards were sent home to parents. At the same time, families were
involved in 27 group therapy meetings plus 8 individual family meetings. Of the
children receiving medication, 75% received methylphenidate, 10% received
dextroamphetamine, and 15% received pemoline, imipramine, clonidine, guanfacine,
or bupropion. After the 14-month study, it was concluded that drug treatment was
more effective than behavioral treatment according to parents’ and teachers’ ratings
of inattention, and teachers’ ratings of hyperactivity/impulsivity. Combined treatment
(drug treatment plus behavioral modification) was preferred by parents, but the
therapeutic advantage versus medication did not achieve statistical significance.
Combined treatment was significantly more effective than behavioral treatment and
community care for reducing ADHD symptoms, according to both parent and teacher
reports, but a subgroup analysis of children with comorbid conditions (e.g., conduct,
oppositional defiant, anxiety, or affective disorders) found behavior management to
be as effective as monotherapy. A 3-year follow-up study revealed that all four
interventions were equally effective in improving academic performance and social
functioning with time, but given the costly and labor-intensive nature of the
behavioral modification, in particular pharmacotherapy, it continues to be regarded
as the first-line treatment for children with at least moderate ADHD symptoms.
There have been a variety of school-based, clinic-based, and home-based
interventions to address ADHD symptoms, mainly with positive results.
Additionally, specialized summer treatment programs have been established to
provide more intensive intervention when school is not in session.
Stimulants are considered the most effective option to treat ADHD, with more than
60 years of clinical experience accrued. Currently there are two basic types of
stimulants marketed in the United States, methylphenidate based and amphetamine
based, and they have all been reported to improve academic performance and
behavior in children with ADHD (Table 89-2).
Overview of Common Drugs to Treat Attention Deficit Hyperactivity Disorder
Methylphenidate C-II Aptenso XR
Dexmethylphenidate C-II Focalin
Dextroamphetamine C-II Dexedrine
Vyvanse Long 30–70 mg a day 30–70 mg a day
Methamphetamine Desoxyn Long 5–25 mg a day No approved
Noradrenergic Reuptake Inhibitor
Atomoxetine Strattera Long 40–100 mg a day 40–100 mg a
disintegrating tablet; CD, controlled delivery.
A review of short-term clinical trials that evaluated the safety and efficacy of
stimulants in nearly 6,000 children and adults with ADHD showed a 75% to 80%
improvement in patients treated with stimulants compared with 5% to 30% treated
36 Although stimulant drugs are grouped as a class based on their
pharmacologic effect of increasing dopamine and norepinephrine levels in the
synapse, the mechanisms by which stimulant drugs exert this effect varies slightly.
These subtle differences in the mechanism of action support the possibility that
patients who respond partially to one stimulant may respond completely to another. In
fact, approximately 20% to 25% of those who respond poorly to one medication will
respond positively to another and up to 90% of children will respond if both are
37 Stimulants also are rapid acting and have predictable effects, with response
Methylphenidate and dexmethylphenidate block the reuptake of dopamine from the
synaptic cleft into the presynaptic neuron via the dopamine transporter protein.
Methylphenidate is metabolized into ritalinic acid via carboxylesterase CES1A1, a
The most common side effects of methylphenidate include appetite suppression,
insomnia, headache, nausea and vomiting, and abdominal pain.
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