AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Attention deficit hyperactivity disorder (ADHD) is a developmental condition of inattention and distractibility, with or without accompanying hyperactivity. In the past, various terms were used to describe this condition, including hyperactive syndrome and, from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III), "minimal brain dysfunction." In the revised DSM-III, this condition was renamed ADHD. In the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR), adults or children must have had an onset of symptoms before age 7 years that caused significant social or academic impairment. More recently, attention has focused on adult forms of ADHD, which probably have been underdiagnosed.

Pathophysiology

The pathology of ADHD is not clear. Psychostimulants (which facilitate dopamine release) and noradrenergic tricyclics used to treat this condition have led to speculation that certain brain areas related to attention are deficient in neural transmission. PET scan imaging indicates that methylphenidate acts to increase dopamine.¹ The neurotransmitters dopamine and norepinephrine have been associated with ADHD.

The underlying brain regions predominantly thought to be involved are frontal and prefrontal; the parietal lobe and cerebellum may also be involved. In one functional MRI study, children with ADHD who performed response-inhibition tasks were reported to have differing activation in frontal-striatal areas compared to healthy controls. Adults with ADHD also have been reported to have deficits in anterior cingulate activation while performing similar tasks.

Individuals with ADHD have inhibition impairment, which is difficulty stopping their responses.³

Frequency

United States

Incidence in school-age children is estimated to be 3-7%.

International

In Great Britain, incidence is reported to be less than 1%. The differences between the US and British reported frequencies may be cultural ("environmental expectations") and due to the heterogeneity of ADHD (ie, the many etiological paths to get to inattention/distractibility/hyperactivity). Furthermore, the International Classification of Diseases, 10th Revision (ICD-10) criteria for ADHD used in Great Britain may be considered stricter than the DSM-IV-TR criteria. However, other studies suggest that the worldwide prevalence of ADHD is between 8% and 12%.

Mortality/Morbidity

• No clear correlation with mortality exists in ADHD. However, studies suggest that childhood ADHD is a risk factor for subsequent conduct and substance abuse problems, which can carry significant mortality and morbidity.
• ADHD may lead to difficulties with academics or employment and social difficulties that can profoundly affect normal development. However, exact morbidity has not been established.

Sex

• In children, ADHD is 3-5 times more common in boys than in girls. Some studies report an incidence ratio of as high as 5:1. The predominantly inattentive type of ADHD is found more commonly in girls than in boys.
• In adults, the sex ratio is closer to even.

Age

• ADHD is a developmental disorder that requires an onset of symptoms before age 7 years. After childhood, symptoms may persist into adolescence and adulthood, or they may ameliorate or disappear.
• The percentages in each group are not well established, but at least an estimated 15-20% of children with ADHD maintain the full diagnosis into adulthood. As many as 65% of these children will have ADHD or some residual symptoms of ADHD as adults.
• The prevalence rate in adults has been estimated at 2-7%.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The 3 types of attention deficit hyperactivity disorder (ADHD) are (1) predominantly hyperactive, (2) predominantly inattentive, and (3) combined. The DSM-IV-TR criteria are as follows⁴:

• Inattention - Must include at least 6 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)
  • Often is easily distracted by extraneous stimuli
  • Often forgetful in daily activities
• Hyperactivity/impulsivity - Must include at least 4 of the following symptoms of hyperactivity-impulsivity that must have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:
• • Hyperactivity evidenced by fidgeting with hands or feet, squirming in seat
  • Hyperactivity evidenced by leaving seat in classroom or in other situations in which remaining seated is expected
  • Hyperactivity evidenced by running about or climbing excessively in situations where this behavior is inappropriate (in adolescents or adults, this may be limited to subjective feelings of restlessness)
  • Hyperactivity evidenced by difficulty playing or engaging in leisure activities quietly
  • Impulsivity evidenced by blurting out answers to questions before the questions have been completed
  • Impulsivity evidenced by showing difficulty waiting in lines or awaiting turn in games or group situations
• Onset is no later than age 7 years.
• Symptoms must be present in 2 or more situations, such as school, work, or home.
• The disturbance causes clinically significant distress or impairment in social, academic, or occupational functioning.
• Disorder does not occur exclusively during the course of a pervasive developmental disorder, schizophrenia, or other psychotic disorder and is not better accounted for by mood, anxiety, dissociative, or personality disorder.
• Numeric codes indicating type based on criteria (adapted from DSM-IV-TR) are as follows:
• • 314.00 ADHD: Predominantly inattentive type if inattention criterion is met for the past 6 months, but hyperactivity/impulsivity criterion is not met
  • 314.01 ADHD: Predominantly hyperactive/impulsive type if hyperactivity/impulsivity criterion is met for the past 6 months, but inattention criterion is not met
  • 314.01 ADHD: Combined type if both inattention and hyperactivity/impulsivity criteria are met for past 6 months (Note that this code is the same as that used for the predominantly hyperactive type.)
  • 314.9 ADHD not otherwise specified (NOS): Other disorders with prominent symptoms of attention-deficit or hyperactivity-impulsivity that do not meet DSM-IV-TR criteria

Physical

• No physical findings have been well correlated with ADHD.
• Mental Status Examination may note the following:
• • Appearance: Most often, appointments are difficult to structure and maintain due to hyperactivity and distractibility. Children with ADHD may present as fidgety, impulsive, and unable to sit still, or they may actively run around the office. Adults with ADHD may be distractible, fidgety, and forgetful.
  • Affect/mood: Affect usually is appropriate and may be elevated, but it should not be euphoric. Mood usually is euthymic, except for periods of low self-esteem and decreased (dysthymic) mood. Mood and affect are not primarily affected by ADHD, although irritability may frequently be associated with ADHD.
  • Speech/thought processes: Speech is of normal rate but may be louder due to impulsivity. Thought processes are goal-directed but may reflect difficulties staying on a topic or task. Evidence of racing thoughts or pressured speech should not be present. These symptoms are more consistent with a manic state (bipolar disorder).
  • Hallucinations or delusions: Not present.
  • Thought content/suicide: Content should be normal, with no evidence of suicidal/homicidal or psychotic symptoms.
  • Cognition: Concentration and storage into recent memory are affected. Patients with ADHD may have difficulty with calculation tasks and recent memory tasks. Orientation, remote memory, or abstraction should not be affected.

ADHD is associated with a number of other clinical diagnoses. Studies have a demonstrated that many individuals have both ADHD and antisocial personality disorder (ASD).⁵ These individual are at higher risk for self-injurious behaviors. ADHD is also linked to addictive behavior. The more severe the symptoms of ADHD, the greater the use of tobacco, alcohol, and marijuana.⁶ Some individuals have both ADHD and an autism spectrum disorder.⁷

Causes

• Genetics
• • Parents and siblings of children with ADHD are 2-8 times more likely to develop ADHD than the general population, suggesting that ADHD is a highly familial disease.
  • Concordance of ADHD in monozygotic twins is greater than in dizygotic twins, suggesting some contribution of genetics. Studies estimate the mean heritability of ADHD to be 76%, indicating that ADHD is one of the most heritable psychiatric disorders.
  • The involved genes or chromosomes are not definitively known. Vulnerability to ADHD may be due to many genes of small effect. For example, several genes that code for dopamine receptors or serotonin products, including DRD4, DRD5, DAT, DBH, 5-HTT, and 5-HTR1B, have been moderately associated with ADHD.
  • ADHD risk is significantly increased in the presence of one risk allele in genes DRD2 (OR=7,5), 5-HTT (OR=2,7), and DAT1 (OR=1,6). ADHD risk is significantly increased at homozygotes for risk alleles in genes DRD2 (OR=54,8), 5-HTT (OR=6,7), and DAT1 (OR=6,6).⁸
  • Studies of cognitive deficits reveal another facet to the genetic contributions to ADHD.⁹
• Environment
• • Hypotheses exist that include in utero exposures to toxic substances, food additives or colorings, or allergic causes. However, diet, especially sugar, is not a cause of ADHD.
  • How much of a role family environment has in the pathogenesis of ADHD is unclear, but it certainly may exacerbate symptoms.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Generalized resistance to thyroid hormone
Learning disorders
Malnutrition
Medication-induced hyperactivity
Metabolic disturbances
Hearing impairment

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The diagnosis of attention deficit hyperactivity disorder (ADHD) is based on clinical evaluation. No laboratory-based medical tests are available to confirm the diagnosis.
• Basic laboratory studies that may help confirm diagnosis and aid in treatment are as follows:
• • Serum CBC count with differential
  • Electrolyte levels
  • Liver function tests (before beginning stimulant therapy)
  • Thyroid function tests

Imaging Studies

• Brain imaging, such as functional MRI or single photon emission computed tomography (SPECT) scans have been useful for research, but no clinical indication exists for these procedures because the diagnosis is clinical.

Other Tests

• Psychological testing
• • The Conners Parent-Teacher Rating Scale is a questionnaire that can be given to both the parents and the child's teachers.
  • Barkley Home Situations Questionnaire may be useful.
  • The Wender Utah Rating Scale may be helpful in diagnosing ADHD in adults.
  • The Continuous Performance Tests (CPTs) are computer-based tasks that often are used to test attention and may be used in conjunction with clinical information to make a diagnosis. A currently popular example is the Test of Variable Attention (TOVA). While these tests can be supportive of the diagnosis in a full clinical evaluation, they have low sensitivity and specificity and should not be the sole basis for diagnosis.
• Vision and hearing should be checked.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Recent data suggest that carefully crafted stimulant therapy is more effective than behavioral therapy or regular community care (medication management by primary care provider). This finding has been born out for the treatment of adults with ADHD as well. Stimulants represent the best first-line therapeutic option.¹⁰ For related areas of functioning, such as social skills and academic performance, medications combined with behavioral treatments may be indicated. Pharmacotherapy includes the following:

• Stimulants (methylphenidate, dextroamphetamine)
• • These are first-line therapy and probably the most effective treatment.
  • All stimulants have similar efficacy but differ by dosing, duration of action, and adverse effect profiles in individual patients. Care should be made to start at the lowest dose and titrate up for clinical efficacy or to intolerance.
  • Targeted symptoms include impulsivity, distractibility, poor task adherence, hyperactivity, and lack of attention.
  • Some stimulants come in sustained-release preparations, which may decrease the number of total daily doses. Otherwise, dosing should be spaced every 4-6 hours.
  • Care should be taken to not dose too close to bedtime because stimulants may cause significant insomnia.
  • Other common adverse effects include appetite suppression and weight loss, headaches, and mood effects (depression, irritability).
  • Stimulants may exacerbate tics in children with underlying tic disorders.
  • Whether growth might be affected while a child is taking stimulants remains unclear. Drug holidays (during summer or on weekends) may or may not be recommended to allow periods of normal growth. The decision is based on the child's growth rate chart and behavior and cognition off medication.
  • There has been a long concern that the use of stimulate therapy leads to substance abuse. Recent studies have demonstrated that stimulant therapy does not increase the risk of future substance use or abuse.¹¹ Furthermore, 112 people with ADHD were observed for a period of 10 years. At the time of the follow-up assessment, 82 (73%) had been treated previously with stimulants and 25 (22%) were undergoing stimulant treatment. No statistically significant associations were noticed between stimulant treatment and alcohol, drug, or nicotine use disorders. The findings revealed no evidence that stimulant treatment increases or decreases the risk for subsequent substance use disorders in children and adolescents with ADHD when they reach young adulthood.¹²
  • Stimulant medications do enhance mental executive functions for those with ADHD.¹³
• Atomoxetine (Strattera) has become a second-line and, in some cases, first-line treatment in children and adults with ADHD because of its efficacy and classification as a nonstimulant. However, studies have reported that the overall effect of atomoxetine has not been as extensive as that reported of stimulants.
• Recent data suggest that bupropion or venlafaxine may be effective. Dosages are similar to those used to treat depression.
• Tricyclic antidepressants (imipramine, desipramine, nortriptyline) have been found effective in numerous studies in children with ADHD; however, because of potential adverse effects, they are rarely used for this purpose. If these agents are used, obtain a baseline ECG because these agents can affect cardiac conduction. A few reports have described sudden death in boys taking desipramine, but the exact cause of death was unclear and may have been unrelated to desipramine use.
• Clonidine and guanfacine have been used with mixed reports of efficacy. Sudden deaths have been reported in children taking clonidine with methylphenidate at bedtime. Again, the etiology of these deaths is unclear, and this remains a controversial topic.
• Modafinil (Provigil) has recent placebo-controlled data supporting its efficacy in children with ADHD. This medication may currently be used as a third- or fourth-line treatment.
• Magnesium pemoline (Cylert) had been used in the 1990s, but concerns of rare, potentially fatal hepatotoxicity have made it a rarely used medication.
• Behavioral psychotherapy often is effective when used in combination with an effective medication regimen.
• • Working with parents and schools to ensure environments conducive to focus and attention is necessary.
  • Behavioral therapy or modification programs can help diminish uncertain expectations and increase organization.
  • For adults with ADHD, working to establish ways of decreasing distractions and improving organizational skills may be helpful.

Psychosocial Interventions

Diet

• For decades, speculation and folklore have suggested that foods containing preservatives or food coloring or foods high in simple sugars may exacerbate ADHD. Many controlled studies have examined this question. To date, no adequate data set has confirmed the speculation.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Although health care providers, parents, and teachers have hoped for effective therapies and methods that do not involve medications for children with attention deficit hyperactivity disorder (ADHD), evidence to date supports that the specific symptoms of ADHD are poorly treated without medication. Perhaps the mildest cases of ADHD can be treated with moderate success with environmental restructuring and behavioral therapy, but other than these limited situations, pharmacotherapy often is needed.

Drug Category: Stimulants

These agents are known to treat ADHD effectively.

Drug Category: Atypical antidepressants

Recent studies support efficacy of venlafaxine and bupropion in ADHD. They may have a slower onset of action than stimulants but potentially fewer adverse effects.

Drug Category: Tricyclic antidepressants

See article entitled Depression. Patients may require lower doses for ADHD. They may have a quicker onset of action.

Drug Category: Alpha-adrenergic agonists

Centrally acting antihypertensives clonidine and guanfacine have been used to treat children with ADHD. Inhibition of norepinephrine release in brain may be mechanism of action.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

Psychiatric hospitalization is indicated if the person becomes suicidal or homicidal.

Further Outpatient Care

Regular follow-up is needed long-term for patients with attention deficit hyperactivity disorder (ADHD). Like diabetes or hypertension, ADHD is not an illness for which one can hand the patient a prescription for pills and assume recovery is automatic with the medication.

Prognosis

• Childhood ADHD may confer a higher risk of diagnosis with conduct disorders and substance abuse into adolescence and adulthood. These may be primary coexisting disorders or disorders secondary to untreated or undertreated ADHD.
• Most children with ADHD have relatively good psychiatric outcomes once they reach adulthood.
• At least 15-20% continue to have full ADHD as adults, and as many as 65% may continue to have problematic symptoms of ADHD that interfere with full realization of academic or work potential.

Patient Education

• The educational requirements of these patients and their family members are high. Family members include parents and siblings of children, spouses and children of adults, and grown children of elderly patients. Encouragement of medication use, education on time structuring and behavioral control, social skill training, and frequent cognitive redirecting is needed.
• For excellent patient education resources, visit eMedicine's Mental Health and Behavior Center. Also, see eMedicine's patient education article Attention Deficit Hyperactivity Disorder.

• Some useful Web sites are as follows:
• • National Institute of Mental Health, Attention Deficit Hyperactivity Disorder (ADHD)
  • National Institute of Neurological Disorders and Stroke, Attention Deficit-Hyperactivity Disorder Information Page
  • CDC, Attention-Deficit/Hyperactivity Disorder (ADHD)
• • In addition, the CDC support the National Resource Center (NRC) on AD/HD: A Program of Children and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD). The NRC is a national information resource center dedicated to providing evidence-based information about ADHD to the public.
  • • If you have a question about ADHD for yourself, your child, or a family member, please contact the NRC.
    • Visit the National Resource Center website.
    • Call 1-800-233-4050 to speak with a knowledgeable health information specialist.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• If the medications used are schedule-II controlled substances (d-amphetamine, methylphenidate), patients should transport the drugs or travel with them in their original pharmacy bottle.
• The event of a stimulant-abusing individual presenting with a complaint of attention deficit hyperactivity disorder (ADHD) in order to get substances to abuse is surprisingly rare. It does occur, however, so remain alert for the possibility.

Special Concerns

• ADHD can be comorbid with the following conditions:
• • Other developmental learning disorders
  • Conduct disorder or oppositional defiant disorder
  • Bipolar disorder
  • Tourette syndrome
  • Pervasive developmental disorder
  • Mental retardation
• When evaluating a patient with any of these disorders, special care should also be made to evaluate for ADHD thoroughly. ADHD, like bipolar disorder, is readily treatable.
• ADHD is a heterogeneic disorder that carries significant comorbidity. Symptoms consistent with ADHD can present as other disorders, or these signs and symptoms could be a precursor in childhood to later disorders such as bipolar disorder or schizophrenia.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: May 21, 2008