Practice Essentials
Attention deficit hyperactivity disorder (ADHD) is a developmental condition of inattention and distractibility, with or without accompanying hyperactivity.
Signs and symptoms
According to the Diagnostic and Statistical Manual of Mental Health Disorders, Fifth Edition, Text Revision (DSM-5-TR), the three types of attention deficit hyperactivity disorder (ADHD) are (1) predominantly inattentive, (2) predominantly hyperactive/impulsive, and (3) combined. The current DSM-5-TR criteria are provided below. [1]
Inattentive
This must include at least six of the following symptoms of inattention that must have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:
-
Often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities
-
Often has difficulty sustaining attention in tasks or play activities
-
Often does not seem to listen to what is being said
-
Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions)
-
Often has difficulties organizing tasks and activities
-
Often avoids or strongly dislikes tasks (such as schoolwork or homework) that require sustained mental effort
-
Often loses things necessary for tasks or activities (school assignments, pencils, books, tools, or toys)
Background
The term attention deficit is misleading. In general, the current predominating theories suggest that persons with attention deficit hyperactivity disorder (ADHD) actually have difficulty regulating their attention; inhibiting their attention to nonrelevant stimuli, and/or focusing too intensely on specific stimuli to the exclusion of what is relevant. In one sense, rather than too little attention, many persons with ADHD pay too much attention to too many things, leading them to have little focus.
Three basic forms of ADHD are described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) of the American Psychiatric Association (APA). [1] They are (1) predominantly inattentive, (2) predominantly hyperactive/impulsive, and (3) combined.
The major neurologic functions disturbed by the neurotransmitter imbalance of ADHD fall into the category of executive function. The six major tasks of executive function that are most commonly distorted with ADHD (ADD) include (1) shifting from one mindset or strategy to another (ie, flexibility), (2) organization (eg, anticipating both needs and problems), (3) planning (eg, goal setting), (4) working memory (ie, receiving, storing, then retrieving information within short-term memory), (5) separating affect from cognition (ie, detaching one's emotions from one's reason), and (6) inhibiting and regulating verbal and motoric action (eg, jumping to conclusions too quickly, difficulty waiting in line in an appropriate fashion).
Contrary to some media accounts, ADHD is not new. In the early 1900s, diagnosis emphasized the hyperactivity component. Today, hyperactivity, impulsivity, and inattention are the areas of focus. However, reports have alluded to disorders involving hyperactivity, impulsivity, and inattention in conjunction with distractibility and inappropriate arousal patterns throughout medical history. What is new is the enhanced awareness of ADHD secondary to rapidly accumulating research findings and its addition to the DSM in 1980.
Pathophysiology
Findings from neuropsychological studies suggest that the frontal cortex and the circuits linking them to the basal ganglia are critical for executive function and, therefore, to attention and exercising inhibition. Many findings support this view, including those described below.
Executive functions are major tasks of the frontal lobes. MRI of the right mesial prefrontal cortex in persons with attention deficit hyperactivity disorder (ADHD) strongly supports decreased activation (low arousal) during tasks that require inhibition of a planned motor response and timing of a motor response to a sensory cue. MRI in persons with ADHD also strongly supports weakened activity in the right inferior prefrontal cortex and left caudate during a task that involves timing of a motor response to a sensory cue.
In an effort to explore neural correlates that mediate response inhibition deficits in children with ADHD, Spinelli, et al examined functional MRI brain activation patterns of children aged 8–13 years with and without ADHD on a go/no-go task. While lapses in attention preceded response inhibition errors in the children without ADHD, brain circuitry involved in response selection and control was activated prior to errors in the children with ADHD. [5]
The catecholamines are the main neurotransmitters with frontal-lobe function. Catecholamine controlled dopaminergic and noradrenergic neurotransmission appear to be the main targets for medications used to treat ADHD.
A 10-year study by National Institute of Mental Health (NIMH) demonstrated that the brains of children and adolescents with ADHD are 3–4% smaller than those of children without the disorder, and that pharmacologic treatment is not the cause. The more severe patients' ADHD symptoms were, as rated by parents and clinicians, the smaller their frontal lobes, temporal gray matter, caudate nucleus, and cerebellum were.
Data from 357 healthy subjects, obtained from the NIH MRI Study of Normal Brain Development, noted that a thinner cortex and slower cortical thinning was associated with higher attention problem scores, suggesting a link between attention and cortical maturation. [6]
In addition to the role of the neurotransmitters most commonly associated with the frontal lobes and the pathways mentioned above, some investigations have begun exploring a possible role for 5-hydroxytryptamine (5-HT). Although the brain’s motor regions are innervated by 5-HT projections, no connection between 5-HT and ADHD motor pathology has yet been identified. However, connections have been made to attention-related processes. Altered 5-HT activity does appear to be at least part of the cause for difficulties with perceptual sensitivity and the appropriate recognition of the relative significance of stimulation.
Epidemiology
Frequency
The prevalence of attention deficit hyperactivity disorder (ADHD) in children appears to be 3–7%. ADHD is associated with significant psychiatric comorbidity. Approximately 50–60% of individuals with this disorder meet DSM-5-TR criteria for at least one of the possible coexisting conditions, which include learning disorders, restless legs syndrome, ophthalmic convergence insufficiency, depression, anxiety disorders, antisocial personality disorder, substance abuse disorder, and conduct disorder. The likelihood of a person having ADHD (ADD) if a family member has ADHD or one of the disorders commonly associated with ADHD is significant.
People with ADHD have been identified in every country studied, with comparable frequency.
Mortality/morbidity
The morbidity for ADHD widely varies. This range is a function of many factors, including the specific area of deficit, the patient's environmental response to and interaction with the deficits, the therapy provided, and the presence of coexistent conditions.
Sex
ADHD is more frequently diagnosed in boys than in girls. Most estimates of the male-to-female ratio range between 3:1 and 4:1 in clinic populations. However, many community-based samples produce a ratio of 2:1. Recognition of ADHD has improved over the last decade, and the male-to-female ratio has been decreasing; this may be the result of the increased recognition of inattentive ADHD.
Age
Data concerning the likelihood that a child with ADHD will also have the disorder as an adult are conflicting. As definitions of ADHD subtypes improve, some subtypes that cause more adult dysfunction than others will likely be found.
Approximately 30–80% of children with ADHD have the disorder as adults. Most experts believe that the rate is well above 50%.
Hyperactive symptoms may decrease with age because of developmental trends toward self-control and changes in brain composition (ie, pruning of abundant neural connections) that occur during late adolescence. However, persons with ADHD developmentally mature later than the average population. Inattentive symptoms do not appear to have a similar developmental advantage and tend to remain constant into adulthood.
Prognosis
The prognosis for patients with attention deficit hyperactivity disorder (ADHD) is excellent if the following conditions are present:
-
The patient has no major comorbidity.
-
Medication management takes into account minor comorbidities and the great range of individual responses.
-
Patients and caregivers receive appropriate education about ADHD and ADHD management.
-
Adherence to therapy continues.
-
Any and all coexisting learning disabilities are diagnosed, and remediation is scheduled and undertaken.
-
Any and all coexisting emotional problems are investigated and treated appropriately by a primary care provider or the patient is referred to a mental health professional.
Patient Education
Provide information about the pathophysiology in lay terms.
Provide information about complementary therapeutic approaches to medication (eg, involvement of education specialists, counseling or coaching, school accommodations, parent training).
Provide clinical medication information.
Include appropriate follow-up parameters.
Attend to administrative issues related to medication (eg, prescription writing and safety, compliance with state laws).
Provide emergency information.
Seek school accommodations.
Provide contact information for local and national support organizations.
Provide literature or written resources (eg, books, periodicals).
Tables
Medication |
Initial Pediatric Dose |
Pediatric Dosage Range and Maximum Dose* |
Common Pediatric Dose* |
Preparations |
Methylphenidate immediate release (IR) (Ritalin, Methylin, generic) |
2.5-5 mg |
0.1-0.8 mg/kg/dose PO qd to 5 times/d; not to exceed 60 mg/d |
0.3-0.5 mg/kg/dose PO tid/qid |
All preparations available as 5-mg, 10-mg, or 20-mg scored tabs; Methylin also available as 2.5-mg, 5-mg, or 10-mg chewable tab and PO solution (5 mg/5 mL and 10 mg/mL) |
Methylphenidate sustained-release (SR) (Ritalin LA, Metadate CD) |
Convert from IR or use 10 mg. |
0.2-1.4 mg/kg/dose PO qd/tid; not to exceed 60 mg/d |
0.6-1 mg/kg/dose PO qd/bid |
10-mg, 20-mg, 30-mg, or 40-mg tabs (Metadate also has 50-mg and 60-mg tabs.); can be sprinkled into soft food (Do not cut, crush, or chew.) |
Methylphenidate extended release (ER)‡ (Ritalin SR, Methylin ER, Metadate ER, Quillivant XR, generic SR) |
Convert from IR May initiate treatment with Quillivant XR |
0.2-1.4 mg/kg/dose PO qd/tid; not to exceed 60 mg/d Quillivant XR: Once daily dosing |
0.6-1 mg/kg/dose PO qd/bid |
20-mg Spansules (Do not cut, crush, or chew) Quillivant XR 5 mg/mL suspension |
Methylphenidate OROS tablets (Concerta) |
Convert from IR or use 18 mg. |
0.3-2 mg/kg PO qd; not to exceed 54 mg/d |
0.8-1.6 mg/kg PO qd |
18-mg, 27-mg, 36-mg, and 54-mg tabs (Do not cut, crush, or chew.) |
Methylphenidate Delay-release/extended-release (Jornay PM) |
20 mg PO at 8 pm | Titrate weekly in increments of 20 mg; not to exceed 100 mg/day | Adjust timing of administration between 6:30 pm and 9:30 pm to optimize tolerability and efficacy the next morning and throughout the day | 20-mg, 40-mg, 60-mg, 80-mg, 100-mg capsules; can be sprinkled into soft food (Do not cut, crush, or chew) |
Methylphenidate transdermal patch (Daytrana)† |
Convert from IR or use 10 mg (12.5 cm2 patch) released over 9 h and titrate up prn. |
0.3-2 mg/kg released over 9 h; not to exceed one 30-mg patch |
10-30 mg released over 9 h |
10-mg, 15-mg, 20-mg, 30-mg patches, applied to the hip |
Dexmethylphenidate IR (Focalin) |
2.5-5-mg |
0.1-0.5 mg/kg/dose PO qd to qid; not to exceed 20 mg/d |
0.2-0.3 mg/kg/dose PO bid/tid |
2.5-mg, 5-mg, or 10-mg scored tabs (Do not cut, crush, or chew.) |
Dexmethylphenidate extended release (Focalin-XR) |
5-10-mg |
0.2-1 mg/kg/dose PO qd to bid; not to exceed 20 mg/d |
0.4-0.6 mg/kg/dose PO qd/bid |
5-mg, 10-mg, or 20-mg scored tabs; can be sprinkled into soft food (Do not cut, crush, or chew.) |
| Serdexmethylphenidate/dexmethylphenidate (Azstarys) | 26.1mg/5.2mg | After 1 week, increase to 52.3 mg/10.4 mg qAM
OR
Decrease to 26.1 mg/5.2 qAM |
Not to exceed 52.3 mg/10.4 mg | Capsules: 26.1mg/5.2mg; 39.2mg/7.8mg; 52.3mg/10.4mg
May open capsule and sprinkle entire contents into 50 mL of water or over 2 tablespoons of applesauce |
Dextroamphetamine (Dexedrine, Dextrostat) |
2.5-5 mg |
0.1-0.7 mg/kg/dose PO qd/qid; not to exceed 60 mg/d |
0.3-0.5 mg/kg/dose PO qd/tid |
Dexedrine: 5-mg scored tabs; Dextrostat: 5-mg and 10-mg scored tabs |
Dextroamphetamine Spansules (Dexedrine CR) |
5 mg |
0.1-0.75 mg/kg/dose PO qd/bid; not to exceed 60 mg/d |
0.3-0.6 mg/kg/dose PO qd/bid |
5-mg, 10-mg, or 15-mg Spansules; can be sprinkled into soft food (Do not cut, crush, or chew.) |
| Dextroamphetamine Transdermal (Xelstrym) | 6-17 years: Apply 4.5 mg/9 hr patch initially |
May increase by increments of 4.5 mg/week; not to exceed 18 mg/9 hr Titrate dose according to patient’s clinical response and tolerability |
4.5 mg/9hr to 18 mg/9hr |
Apply to application site 2 hr before an effect is needed and remove within 9 hr after application
Use only 1 patch/24 hr |
Mixed amphetamine salts IR (Adderall, generic) |
2.5-5 mg |
0.1-0.7 mg/kg/dose PO qd/qid; not to exceed 40 mg/d |
0.3-0.5 mg/kg/dose PO tid/qid |
5-mg, 7.5-mg, 10-mg, 12.5-mg, 15-mg, 20-mg, or 30-mg scored tabs |
Mixed amphetamine salt XR (Adderall-XR) |
Convert from IR or use 5-10 mg |
0.2-1.4 mg/kg/dose PO qd/tid Not to exceed 30 mg/d |
0.6-1 mg/kg/dose PO qd/bid |
5-mg, 10-mg, 15-mg, 20-mg, 25-mg, or 30-mg Spansules; can be sprinkled into soft food (Do not cut, crush, or chew.) |
Lisdexamfetamine (Vyvanse) |
30 mg PO qam |
30-70 mg PO qam |
Data limited |
20-mg, 30-mg, 40-mg, 50-mg, 60-mg, or 70-mg caps (Swallow cap whole, sprinkle into soft food, or dissolve contents in glass of water and drink immediately.)Risk of apnea in patients with chronic pulmonary disease; closely monitor these patients, when initiating and titrating therapy; alternatively, consider the use of alternative non-opioid analgesics in these patients (see Black Box Warnings and Contraindications) |
| Amphetamine (Evekeo, Dyanavel XR), Adzenys XR-ODT | Evekeo: 2.5 mg PO BID/TID
Dyanavel XR: 2.5-5 mg PO once daily
Adzenys XR-ODT: 6.3 mg PO qAM |
Evekeo: 2.5 mg BID/TID; only in rare cases is it necessary to exceed 40 mg/day
Dyanavel XR: 2.5-5 mg/day; not to exceed 20 mg/day
Adzenys XR-ODT: Not to exceed 18.8 mg/day (aged 6-12 y) or 12.5 mg/day (aged 13-17 y) |
Data limited | Evekeo: 5-mg, 10-mg tablets
Dyanavel XR: 2.5-mg/mL extended-release oral suspension (do not substitute oral suspension for other amphetamine products on a milligram-per-milligram basis)
Adzenys XR-ODT: 3.1-mg, 6.3-mg, 9.4-mg, 12.5-mg, 15.7-mg, 18.8-mg extended-release oral disintegrating tablets |
Note. In general, when the terms methylphenidate, Dexedrine, and Ritalin are used without abbreviations for extended-release preparations (eg, continuous release [CR], SR, osmotic-release oral system [OROS]), a short-acting, IR preparation is implied. * Maximum pediatric dose suggested by the US Food and Drug Administration (FDA). Although some children benefit greatly from doses greater than these, benefit from use of either the lowest and highest ends of the dose range is uncommon. †The methylphenidate patch contains a different total methylphenidate dose than the name implies because it is designed to last 12 hours (eg, 10-mg patch [patch size 12.5 cm2] delivers about 10 mg over 9 h [estimated delivery rate is 1.1 mg/h for this particular patch]). Delivery rate varies depending on patch size. ‡Many patients describe their experience with methylphenidate SR preparations as erratic and uncomfortable. |
||||
