eMedicine Specialties > Psychiatry > Child

Attention Deficit Hyperactivity Disorder

Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA
Kiki D Chang, MD, Director, Pediatric Bipolar Disorders Clinic, Associate Professor, Department of Psychiatry, Division of Child Psychiatry, Stanford University School of Medicine

Updated: Aug 12, 2008

Introduction

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

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.

Differential Diagnoses

Other Problems to Be Considered

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

Workup

Laboratory 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

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

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.

Stimulants

These agents are known to treat ADHD effectively.

Methylphenidate (Ritalin, Metadate CD, Methylin ER, Ritalin SR)

DOC approved by FDA for ADHD in children aged 6 y or older. Most commonly used drug. Available in sustained-release forms.

Dosing

Adult

5 mg/d PO in am or divided bid; not to exceed 60 mg/d (stated in Physicians Desk Reference, but some selected individuals benefit from a somewhat higher dose without apparent adverse reactions)

Pediatric

IR: 2.5-5 mg PO up to qid, initial dose
Ritalin SR or Methylin ER: 10-20 mg/d PO initial dose
Metadate CD: 20 mg/d PO initial dose
Concerta: 18 mg/d PO, initial (unless replacing higher short-acting dose that is known as acceptable for patient)

Interactions

Reduces effects of guanethidine and bretylium; toxicity of phenytoin, tricyclic antidepressants, warfarin, primidone, and phenobarbital may increase when administered concurrently; MAOIs increase toxicity

Contraindications

Documented hypersensitivity; glaucoma, Tourette syndrome, motor tics; patients with agitation, tension, and anxiety; untreated hypertension; untreated glaucoma; substance abuse may be a relative contraindication in some patients (patients with untreated ADHD have higher rates of substance abuse than those treated for ADHD)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in dementia, seizures, and hypertension; potentially addictive

Dexmethylphenidate (Focalin, Focalin XR)

Contains the more pharmacologically active d-enantiomer of racemic methylphenidate. Blocks norepinephrine and dopamine reuptake into presynaptic neuron and increases release of these monamines into extraneuronal space. To allow once-daily dosing, each extended-release (XR) cap contains half the dose as immediate-release and half as enteric-coated, delayed-release.

Dosing

Adult

Focalin: 2.5 mg PO bid (if not currently taking racemic methylphenidate); if patient currently taking dexmethylphenidate, initiate dose at half that of methylphenidate; not to exceed 20 mg/d

Focalin XR (not currently taking dexmethylphenidate or racemic methylphenidate): 10 mg/d PO initially, may increase to 20 mg/d after 1 wk if warranted; not to exceed 20 mg/d

Focalin XR (currently taking dexmethylphenidate [Focalin]): Administer same total daily dose as Focalin but administer qd

Focalin XR (currently taking racemic methylphenidate): Switch to half total daily dose and administer qd; not to exceed 20 mg/d

Pediatric

<6 years: Not established
>6 years:
Focalin: 2.5 PO bid initially, may increase in 2.5- to 5-mg increments qwk if warranted; not to exceed 20 mg/d
Focalin XR: (not currently taking dexmethylphenidate or racemic methylphenidate): 5 mg/d PO initially, may increase in 5-mg increments qwk if warranted; not to exceed 20 mg/d
Focalin XR (currently taking dexmethylphenidate [Focalin]): Administer the same total daily dose as Focalin but administer qd
Focalin XR (currently taking racemic methylphenidate): Switch to half total daily dose and administer qd; not to exceed 20 mg/d

Interactions

Coadministration with MAOIs or within 14 d following discontinuation of MAOIs may result in hypertensive crisis and is contraindicated; coadministration with other vasopressors (eg, pseudoephedrine) may increase blood pressure; may counteract effect of antihypertensive drugs; may inhibit metabolism of warfarin, anticonvulsants (eg, phenobarbital, phenytoin, primidone), and TCAs (eg, imipramine, clomipramine, desipramine); serious adverse events reported with concomitant clonidine, although no causality established

Contraindications

Documented hypersensitivity to dexmethylphenidate or methylphenidate; marked anxiety, tension, or agitation; glaucoma; motor tics or Tourette syndrome; coadministration with MAOIs or within 14 d following discontinuation of MAOIs

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Not intended to treat severe depression or fatigue states; may exacerbate psychosis; may lower seizure threshold in patients with prior history or EEG abnormalities; may cause visual disturbances and increase blood pressure; caution with history of drug dependence or alcoholism; monitor CBC count, differential, and platelet count periodically with prolonged therapy; common adverse effects include nervousness, insomnia, decreased appetite, abdominal pain, and weight loss; XR formulation must be swallowed whole or sprinkled on a spoonful of applesauce (do not crush, chew, or divide)

Magnesium pemoline (Cylert)

Less frequently used because of rare but potential hepatotoxic effects and slower onset of action.
The United States Food and Drug Administration (FDA) concluded that the overall risk of liver toxicity from pemoline outweighs the benefits. In May 2005, Abbott chose to stop sales and marketing of their brand of pemoline (Cylert) in the U.S. In October 2005, all companies that produced generic versions of pemoline also agreed to stop sales and marketing of pemoline.

Dosing

Adult

37.5-112.5 mg/d PO

Pediatric

<6 years: Not established
>6 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; hepatic dysfunction

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with renal insufficiency; perform liver function tests prior to and during therapy

Dextroamphetamine and amphetamine mixtures (Adderall)

Produces CNS and respiratory stimulation. The CNS effect may occur in the cerebral cortex and reticular activating system. May have direct effect on both alpha- and beta-receptor sites in the peripheral system as well as release stores of norepinephrine in adrenergic nerve terminals.
Mixture contains various salts of amphetamine and dextroamphetamine.
Available as 5-, 7.5-, 10-, 12.5-, 15-, 20-, and 30-mg scored tablets.

Dosing

Adult

5-60 mg/d PO divided bid/tid

Pediatric

<3 years: Not established
3-6 years: 2.5 mg/d PO initially; increase by 2.5 mg qwk
>6 years: 5 mg/d PO or divided bid initially; increase by 5 mg qwk; not to exceed 40 mg/d

Interactions

Coadministration with MAOIs may precipitate hypertensive crisis; anesthetics may precipitate arrhythmias; dextroamphetamine may increase toxicity of phenobarbital, propoxyphene, meperidine, TCAs, phenytoin, and norepinephrine

Contraindications

Documented hypersensitivity; hypertension; advanced arteriosclerosis; hyperthyroidism; glaucoma; agitated states; within 14 d of MAOIs administration

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in nephritis, hypertension, angina, glaucoma, cardiovascular disease, psychopathic personalities, or history of drug abuse

Atomoxetine (Strattera)

Elicits selective inhibition of the presynaptic norepinephrine transporter. Used to improve symptoms of ADHD.

Dosing

Adult

40 mg/d PO initially; after 3 d, increase up to 80 mg/d PO or divided bid (morning and late afternoon); may increase dose further after 2-4 wk; not to exceed 100 mg/d

Pediatric

<70 kg: 0.5 mg/kg/d PO initially; after 3 d, increase to 1.2 mg/kg/d PO or divided bid (morning and late afternoon); not to exceed 1.4 mg/kg/d or 100 mg/d (whichever is less)
>70 kg: Administer as in adults

Interactions

Eliminated primarily via CYP450 2D6 isoenzyme (thus, enzyme inhibitors [eg, fluoxetine, paroxetine, quinidine] may increase atomoxetine levels); coadministration with vasopressors may increase HR and BP; do not use within 2 wk of MAOIs

Contraindications

Documented hypersensitivity; do not use MAOIs within 2 wk; narrow-angle glaucoma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Decrease dose with moderate-to-severe hepatic dysfunction; rare allergic reactions (eg, angioneurotic edema, urticaria, rash) have been reported; caution in patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease; may increase BP or HR; may cause urinary hesitancy or orthostatic hypotension; monitor growth (may decrease weight)

Dextroamphetamine (Dexedrine)

Commonly used first or in case of methylphenidate failure. Approved by FDA for use in children aged 3 y or older. Available in sustained-release forms, which may allow for daily dosing.

Dosing

Adult

Initial: 5 mg/d PO; not to exceed 40 mg/d (as listed in the Physicians Desk Reference); some selected patients may benefit from a slightly higher dose without adverse reaction

Pediatric

>6 years: 2.5 mg/d PO; may titrate up by 2.5 mg/d once or twice weekly

Interactions

Coadministration with MAOIs may precipitate hypertensive crisis and with anesthetics may precipitate arrhythmias; may increase toxicity of phenobarbital, propoxyphene, meperidine, tricyclic antidepressants, phenytoin, and norepinephrine

Contraindications

Documented hypersensitivity; hypertension; MAOIs; advanced arteriosclerosis; hyperthyroidism; glaucoma; substance abuse may be a relative contraindication is some patients (patients with untreated ADHD have higher rates of substance abuse than those treated for ADHD)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in angina, glaucoma, cardiovascular disease, and psychopathic personalities; potentially addictive

Lisdexamfetamine (Vyvanse)

Inactive prodrug of dextroamphetamine. Elicits CNS stimulant activity. Blocks norepinephrine and dopamine reuptake in presynaptic neurons and increases release of these monoamines in extraneuronal space. Indicated for ADHD for children aged 6 years or older.

Dosing

Adult

30 mg PO every am; if needed may increase by 20-mg/d increments at weekly intervals; not to exceed 70 mg/d

Pediatric

<6 years: Not established
>6 years: Administer as in adults
Swallow cap whole or dissolve contents in glass of water and drink immediately

Interactions

Reduces effects of guanethidine and bretylium; toxicity of phenytoin, tricyclic antidepressants, warfarin, primidone, phenobarbital, meperidine, and vasopressors may increase when administered concurrently; MAOIs increase toxicity of dextroamphetamine

Contraindications

Documented hypersensitivity; advanced arteriosclerosis; symptomatic cardiovascular disease; moderate-to-severe hypertension; hyperthyroidism; glaucoma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in dementia, seizures, hypertension, structural cardiac abnormalities, or other cardiovascular disease; increased risk for sudden death associated with use in patients with serious heart conditions; sudden death, stroke, and MI have also been reported in adults receiving stimulant drugs at usual doses; may exacerbate preexisting psychiatric disorders and increase potential for emergence of treatment-related psychotic or manic symptoms; may increase risk of temporary growth suppression

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.

Bupropion (Wellbutrin)

Inhibits neuronal dopamine reuptake in addition to being a weak blocker of serotonin and norepinephrine reuptake. Also available in sustained-release preparations (Wellbutrin SR)

Dosing

Adult

75 mg/d PO or 100 mg/d SR PO, initially; if initial dose ineffective and higher dose tolerated, increase gradually to maximum 150 mg tid or 200 mg SR bid

Pediatric

Not established, but often used "off label"

Interactions

Carbamazepine, cimetidine, phenytoin, and phenobarbital may decrease effects; toxicity increases with concurrent administration of levodopa and MAOIs

Contraindications

Documented hypersensitivity; seizure disorder; anorexia nervosa; concurrent use with MAOIs

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Doses >400 mg/d of SR preparation or 450 mg/d of immediate-release preparation associated with higher incidence of seizure; caution in patients with renal or hepatic insufficiency

Venlafaxine (Effexor)

May inhibit neuronal serotonin and norepinephrine reuptake. In addition, causes beta-receptor downregulation. Available in sustained-release preparations (Effexor XR)

Dosing

Adult

25 mg/d PO initially and increase as tolerated to 75-375 mg/d PO divided into bid dosing regimen

Pediatric

Not established

Interactions

Cimetidine, MAOIs, sertraline, fluoxetine class I-C antiarrhythmics, tricyclic antidepressants, and phenothiazine may increase effects

Contraindications

Documented hypersensitivity; patients taking MAOIs or who have taken them within 14 d of initiating therapy; uncontrolled hypertension (may cause slight increase in blood pressure at higher doses)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Patients may experience hypertension; fatal reaction may occur if taken concurrently with an MAOI; exercise caution in patients with cardiovascular disorders; may be associated with increased blood pressure at higher doses

Tricyclic antidepressants

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

Imipramine (Tofranil)

Inhibits the reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron. May be useful in pediatric ADHD.

Dosing

Adult

Not established

Pediatric

Initial: 10 mg/d PO; if tolerated and not effective, increase to 25 mg/d; titrate upward slowly by 25 mg/wk to effectiveness or intolerable adverse effects

Interactions

Increases toxicity of sympathomimetic agents such as isoproterenol and epinephrine by potentiating effects and inhibiting antihypertensive effects of clonidine

Contraindications

Problems of slowed or irregular cardiac conduction; untreated glaucoma; recent or concurrent MAOIs

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Overdose may be lethal; may impair mental or physical abilities required for performance of potentially hazardous tasks; caution in patients with cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, or those receiving thyroid replacement therapy

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.

Clonidine (Catapres)

Not approved by FDA for any psychiatric uses in children. However, may be effective in ADHD. Available in tabs or transdermal skin patches.

Dosing

Adult

0.1-0.3 mg PO divided bid/tid

Pediatric

Not established

Interactions

Concurrent CNS depressants may increase effects; tricyclic antidepressants may decrease levels; sudden death reported in patients taking clonidine with methylphenidate at bedtime

Contraindications

Documented hypersensitivity; cardiovascular disease; depressive symptoms

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in cerebrovascular disease, coronary insufficiency, sinus node dysfunction, and renal impairment

Guanfacine (Tenex)

Has similar mechanism of action to clonidine but has longer half-life and may be less sedative. Not recommended for children <12 y.

Dosing

Adult

1-3 mg PO divided bid/tid

Pediatric

Not established

Interactions

Increases effect of other hypotensive agents; tricyclic antidepressants may decrease hypotensive effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in hepatic impairment, severe coronary insufficiency, and recent myocardial infarction

Follow-up

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 NationalResourceCenter website.
• Call 1-800-233-4050 to speak with a knowledgeable health information specialist.

Miscellaneous

Medicolegal 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

1. Rosack J. PET Scans Reveal Action of Methylphenidate in Brain. Psychiatric News. Sept 21, 2001;36, 18.

2. Volkow ND, Wang GJ, Newcorn J, Telang F, Solanto MV, Fowler JS, et al. Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. Aug 2007;64(8):932-40. [Medline].

3. Morein-Zamir S, Hommersen P, Johnston C, Kingstone A. Novel Measures of Response Performance and Inhibition in Children with ADHD. J Abnorm Child Psychol. May 9 2008;[Medline].

4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). 4th ed. Washington, DC: American Psychiatric Association; 2000. 78-85.

5. Semiz UB, Basoglu C, Oner O, Munir KM, Ates A, Algul A, et al. Effects of diagnostic comorbidity and dimensional symptoms of attention-deficit-hyperactivity disorder in men with antisocial personality disorder. Aust N Z J Psychiatry. May 2008;42(5):405-13. [Medline].

6. Upadhyaya HP, Carpenter MJ. Is attention deficit hyperactivity disorder (ADHD) symptom severity associated with tobacco use?. Am J Addict. May-Jun 2008;17(3):195-8. [Medline].

7. Reiersen AM, Todd RD. Co-occurrence of ADHD and autism spectrum disorders: phenomenology and treatment. Expert Rev Neurother. Apr 2008;8(4):657-69. [Medline].

8. Kopecková M, Paclt I, Petrásek J, Pacltová D, Malíková M, Zagatová V. Some ADHD polymorphisms (in genes DAT1, DRD2, DRD3, DBH, 5-HTT) in case-control study of 100 subjects 6-10 age. Neuro Endocrinol Lett. Apr 2008;29(2):246-51. [Medline].

9. Bellgrove MA, O'Connell RG, Vance A. Genetics of cognitive deficits in ADHD: clues for novel treatment methods. Expert Rev Neurother. Apr 2008;8(4):553-61. [Medline].

10. Tcheremissine OV, Salazar JO. Pharmacotherapy of adult attention deficit/hyperactivity disorder: review of evidence-based practices and future directions. Expert Opin Pharmacother. May 2008;9(8):1299-310. [Medline].

11. Volkow ND, Swanson JM. Does childhood treatment of ADHD with stimulant medication affect substance abuse in adulthood?. Am J Psychiatry. May 2008;165(5):553-5. [Medline].

12. Mannuzza S, Klein RG, Truong NL, Moulton JL 3rd, Roizen ER, Howell KH, et al. Age of methylphenidate treatment initiation in children with ADHD and later substance abuse: prospective follow-up into adulthood. Am J Psychiatry. May 2008;165(5):604-9. [Medline].

13. Semrud-Clikeman M, Pliszka S, Liotti M. Executive functioning in children with attention-deficit/hyperactivity disorder: Combined type with and without a stimulant medication history. Neuropsychology. May 2008;22(3):329-40. [Medline].

14. Pelham WE Jr, Fabiano GA. Evidence-based psychosocial treatments for attention-deficit/hyperactivity disorder. J Clin Child Adolesc Psychol. Jan 2008;37(1):184-214. [Medline].

15. Baving L, Laucht M, Schmidt MH. Atypical frontal brain activation in ADHD: preschool and elementary school boys and girls. J Am Acad Child Adolesc Psychiatry. Nov 1999;38(11):1363-71. [Medline].

16. Biederman J, Faraone S, Mick E. Attention-deficit hyperactivity disorder and juvenile mania: an overlooked comorbidity?. J Am Acad Child Adolesc Psychiatry. Aug 1996;35(8):997-1008. [Medline].

17. Biederman J, Faraone S, Milberger S. A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders. Arch Gen Psychiatry. May 1996;53(5):437-46. [Medline].

18. Biederman J, Faraone SV, Milberger S. Is childhood oppositional defiant disorder a precursor to adolescent conduct disorder? Findings from a four-year follow-up study of children with ADHD. J Am Acad Child Adolesc Psychiatry. Sep 1996;35(9):1193-204. [Medline].

19. Bush G, Frazier JA, Rauch SL. Anterior cingulate cortex dysfunction in attention- deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop. Biol Psychiatry. Jun 15 1999;45(12):1542-52. [Medline].

20. Casey BJ, Castellanos FX, Giedd JN. Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. - Sarfatti SE;36(3):374-83. [Medline].

21. Dulcan M. Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder. American Academy of Child and Adolescent Psychiatry. J Am Acad Child Adolesc Psychiatry. Oct 1997;36(10 Suppl):85S-121S. [Medline].

22. Faraone SV, Perlis RH, Doyle AE, et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. Jun 1 2005;57(11):1313-23. [Medline].

23. Faraone SV, Sergeant J, Gillberg C, Biederman J. The worldwide prevalence of ADHD: is it an American condition?. World Psychiatry. Jun 2003;2(2):104-113. [Medline].

24. Green WH. Child and Adolescent Clinical Psychopharmacology. Baltimore, Md: Williams & Wilkins; 1995:56-77.

25. Greenhill LL. Diagnosing attention-deficit/hyperactivity disorder in children. J Clin Psychiatry. 1998;59 Suppl 7:31-41. [Medline].

26. Hauser P, Zametkin AJ, Martinez P. Attention deficit-hyperactivity disorder in people with generalized resistance to thyroid hormone. N Engl J Med. Apr 8 1993;328(14):997-1001. [Medline].

27. Jensen PS. Fact versus fancy concerning the multimodal treatment study for attention-deficit hyperactivity disorder. Can J Psychiatry. Dec 1999;44(10):975-80. [Medline].

28. Kaplan HI, Sadock BJ, Grebb JA. Kaplan and Sadock's Synposis of Psychiatry. 7^th ed. Baltimore, Md: Williams & Wilkins; 1994:1063-8.

29. MTA Cooperative Group. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Arch Gen Psychiatry. Dec 1999;56(12):1073-86. [Medline].

30. Multimodal Treatment Study. Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder: the Multimodal Treatment Study of children with Attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. Dec 1999;56(12):1088-96. [Medline].

31. Rugino TA, Samsock TC. Modafinil in children with attention-deficit hyperactivity disorder. Pediatr Neurol. Aug 2003;29(2):136-42. [Medline].

32. Rutter M, Taylor E, Hersov L. Child and Adolescent Psychiatry: Modern Approaches. 3^rd ed. Oxford, UK: Blackwell Science; 1994:285-307.

33. Shillington AM, Reed MB, Lange JE, Clapp JD, Henry S. College undergraduate Ritalin abusers in Southwestern California: Protective and Risk Factors. J Drug Iss. 2006;36:4:999-1014.

34. Spencer T, Biederman J, Wilens T. Nonstimulant treatment of adult attention-deficit/hyperactivity disorder. Psychiatr Clin North Am. Jun 2004;27(2):373-83. [Medline].

35. Vaidya CJ, Austin G, Kirkorian G. Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study. Proc Natl Acad Sci U S A. Nov 24 1998;95(24):14494-9. [Medline].

36. White BP, Becker-Blease KA, Grace-Bishop K. Stimulant medication use, misuse, and abuse in an undergraduate and graduate student sample. J Am Coll Health. Mar-Apr 2006;54(5):261-8. [Medline].

Keywords

ADHD, attention deficit hyperactivity disorder, hyperactive, hyperactivity, attention deficit disorder, ADD, hyperactive syndrome, minimal brain dysfunction, inattention, distractibility, adult attention deficit hyperactivity disorder, adult attention deficit disorder, adult hyperactivity, adult ADHD, adult ADD, dopamine, norepinephrine, predominantly hyperactive ADHD, predominantly inattentive ADHD, combined ADHD, impulsivity, Tourette syndrome, Tourette disease, Tourette's syndrome, Tourette's disease, bipolar disorder

Contributor Information and Disclosures

Author

Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA
Stephen Soreff, MD is a member of the following medical societies: American College of Mental Health Administration and American Psychosomatic Society
Disclosure: Nothing to disclose.

Coauthor(s)

Kiki D Chang, MD, Director, Pediatric Bipolar Disorders Clinic, Associate Professor, Department of Psychiatry, Division of Child Psychiatry, Stanford University School of Medicine
Kiki D Chang, MD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry and American Psychiatric Association
Disclosure: Abbott Laboratories Consulting fee Consulting; AstraZeneca Grant/research funds None; Lilly Grant/research funds None; Lilly Consulting fee None; Otsuka Consulting fee None; Otsuka Grant/research funds None; GSK  None

Medical Editor

Denis F Darko, MD, Executive Director, Clinical Research and Development, Global Neuroscience, AstraZeneca
Denis F Darko, MD is a member of the following medical societies: American College of Physicians and American Psychiatric Association
Disclosure: AstraZeneca Salary Management position

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Eduardo Dunayevich, MD, Adjunct Assistant Professor, Department of Psychiatry, University of Cincinnati; Clinical Research Physician, Neuroscience, Lilly Research Laboratories
Eduardo Dunayevich, MD is a member of the following medical societies: American Psychiatric Association
Disclosure: Nothing to disclose.

CME Editor

Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry and Department of Medicine, Froedtert Hospital, Medical College of Wisconsin
Harold H Harsch, MD is a member of the following medical societies: American Psychiatric Association
Disclosure: lilly Honoraria Speaking and teaching; Forest Labs Honoraria Speaking and teaching; AstraZeneca Honoraria Speaking and teaching; Pfizer Grant/research funds Speaking and teaching; Northstar Grant/research funds Research; Novartis Grant/research funds research; Pfizer  Speaking and teaching; Sanofi-avetis Grant/research funds research; Otsuke Grant/research funds reseach; GlaxoSmithKline Grant/research funds research

Chief Editor

Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA
Stephen Soreff, MD is a member of the following medical societies: American College of Mental Health Administration and American Psychosomatic Society
Disclosure: Nothing to disclose.

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