Attention Deficit Hyperactivity Disorder

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Synonyms and related keywords: ADHD, attention deficit hyperactivity disorder, hyperactive, hyperactivity, attention d
hyperactive syndrome, minimal brain dysfunction, inattention, distractibility, adult attention deficit hyperactivity disorder, a
disorder, adult hyperactivity, adult ADHD, adult ADD, dopamine, norepinephrine, predominantly hyperactive ADHD, pred
ADHD, combined ADHD, impulsivity, Tourette syndrome, Tourette disease, Tourette's syndrome, Tourette's disease, bipo
AUTHOR INFORMATION Section
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Author: Kiki D Chang, MD, Director, Pediatric Mood Disorders Clinic, Assistant Professor, Departme
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 A
Psychiatry, American Psychiatric Association, and Association for Academic Psychiatry
Editor(s): Denis F Darko, MD, Director, Central Nervous System Clinical Research, Clinical Science
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eduardo Dunayevich, M
Assistant Professor, Department of Psychiatry, University of Cincinnati; Clinical Research Physician,
Lilly Research Laboratories; Harold H Harsch, MD, Program Director of Geropsychiatry, Departmen
Geriatrics/Gerontology, Associate Professor, Department of Psychiatry, Assistant Professor, Departm
Froedtert Hospital, Medical College of Wisconsin; and Stephen Soreff, MD, President of Education
Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA

Disclosure

INTRODUCTION Section 2 of
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Background: Attention deficit hyperactivity disorder (ADHD) is a developmental condition of inatten

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

Pathophysiology: The pathology of ADHD is not clear. Findings indicating that psychostimulants (w
dopamine release) and noradrenergic tricyclics treat this condition have led to speculation that certa
related to attention are deficient in neural transmission. The neurotransmitters dopamine and norepin
associated with ADHD.

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

Frequency:

In the US: Incidence in school-age children is estimated to be 3-7%.

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

Mortality/Morbidity:

No clear correlation with mortality exists in ADHD. However, studies suggest that childhood A
for subsequent conduct and substance abuse problems, which can carry significant mortality

ADHD may lead to difficulties with academics or employment and social difficulties that can pr
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 inc
high as 5:1. The predominantly inattentive type of ADHD is found more commonly in girls than

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. Af
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
maintain the full diagnosis into adulthood. As many as 65% of these children will have ADHD
symptoms of ADHD as adults.

The prevalence rate in adults has been estimated at 2-7%.

 CLINICAL Section 3 of
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

History: The 3 types of attention-deficit/hyperactivity disorder (ADHD) are (1) predominantly hypera
predominantly inattentive, and (3) combined. The DSM-IV-TR criteria are as follows:

Inattention - Must include at least 6 of the following symptoms of inattention that must have pe
months to a degree that is maladaptive and inconsistent with developmental level:

o Often fails to give close attention to details or makes careless mistakes in schoolwork,
activities

o Often has difficulty sustaining attention in tasks or play activities

o Often does not seem to listen to what is being said

o Often does not follow through on instructions and fails to finish schoolwork, chores, or
workplace (not due to oppositional behavior or failure to understand instructions)

o Often has difficulties organizing tasks and activities

o Often avoids or strongly dislikes tasks (such as schoolwork or homework) that require
effort

o Often loses things necessary for tasks or activities (school assignments, pencils, books

o Often is easily distracted by extraneous stimuli

o Often forgetful in daily activities

Hyperactivity/impulsivity - Must include at least 4 of the following symptoms of hyperactivity-im

have persisted for at least 6 months to a degree that is maladaptive and inconsistent with dev

o Hyperactivity evidenced by fidgeting with hands or feet, squirming in seat

o Hyperactivity evidenced by leaving seat in classroom or in other situations in which rem

expected

o Hyperactivity evidenced by running about or climbing excessively in situations where th

 inappropriate (in adolescents or adults, this may be limited to subjective feelings of res

o Hyperactivity evidenced by difficulty playing or engaging in leisure activities quietly

o Impulsivity evidenced by blurting out answers to questions before the questions have b

o Impulsivity evidenced by showing difficulty waiting in lines or awaiting turn in games or

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 occ
functioning.
Disorder does not occur exclusively during the course of a pervasive developmental disorder,
other psychotic disorder and is not better accounted for by mood, anxiety, dissociative, or per
Numeric codes indicating type based on criteria (adapted from DSM-IV-TR) are as follows:

o 314.00 ADHD: Predominantly inattentive type if inattention criterion is met for the past
hyperactivity/impulsivity criterion is not met
o 314.01 ADHD: Predominantly hyperactive/impulsive type if hyperactivity/impulsivity crit
past 6 months, but inattention criterion is not met
o 314.01 ADHD: Combined type if both inattention and hyperactivity/impulsivity criteria a
months (Note that this code is the same as that used for the predominantly hyperactive

o 314.9 ADHD not otherwise specified (NOS): Other disorders with prominent symptoms
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:

o Appearance: Most often, appointments are difficult to structure and maintain due to hyp
distractibility. Children with ADHD may present as fidgety, impulsive, and unable to sit s
actively run around the office. Adults with ADHD may be distractible, fidgety, and forget

o Affect/mood: Affect usually is appropriate and may be elevated, but it should not be eup
is euthymic, except for periods of low self-esteem and decreased (dysthymic) mood. M
not primarily affected by ADHD, although irritability may frequently be associated with A

o Speech/thought processes: Speech is of normal rate but may be louder due to impulsiv
processes are goal-directed but may reflect difficulties staying on a topic or task. Evide
thoughts or pressured speech should not be present. These symptoms are more consi
state (bipolar disorder).

o Thought content/suicide: Content should be normal, with no evidence of suicidal/homic

 symptoms.

o Cognition: Concentration and storage into recent memory are affected. Patients with A
difficulty with calculation tasks and recent memory tasks. Orientation, remote memory,
should not be affected.

Causes:

Genetics

o Parents and siblings of children with ADHD are 2-8 times more likely to develop ADHD
population, suggesting that ADHD is a highly familial disease.

o Concordance of ADHD in monozygotic twins is greater than in dizygotic twins, suggest

contribution of genetics. Studies estimate the mean heritability of ADHD to be 76%, ind
one of the most heritable psychiatric disorders.

o The involved genes or chromosomes are not definitively known. Vulnerability to ADHD
many genes of small effect. For example, several genes that code for dopamine recep
products, including DRD4, DRD5, DAT, DBH, 5-HTT, and 5-HTR1B, have been modera
ADHD.

Environment

o Hypotheses exist that include in utero exposures to toxic substances, food additives or
causes. However, diet, especially sugar, is not a cause of ADHD.

o How much of a role family environment has in the pathogenesis of ADHD is unclear, bu
exacerbate symptoms.

DIFFERENTIALS Section 4 of
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Anxiety Disorders
Bipolar Affective Disorder
Depression
Dysthymic Disorder
Hyperthyroidism
Posttraumatic Stress Disorder
Sleep Disorders

Other Problems to be Considered:

Generalized resistance to thyroid hormone

Learning disorders
Malnutrition
Medication-induced hyperactivity
Metabolic disturbances

WORKUP
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Lab Studies:

The diagnosis of attention-deficit/hyperactivity disorder (ADHD) is based on clinical evaluation

available to confirm the diagnosis.

Basic laboratory studies that may help confirm diagnosis and aid in treatment are as follows:

o Serum CBC count with differential

o Electrolyte levels

o Liver function tests (before beginning stimulant therapy)

o Thyroid function tests

Imaging Studies:

Brain imaging, such as functional MRI or single photon emission computed tomography (SPE
but no clinical indication exists for these procedures because the diagnosis is clinical.

Other Tests:

Psychological testing

o The Conners Parent-Teacher Rating Scale is a questionnaire that can be given to both

o Barkley Home Situations Questionnaire may be useful.

o The Wender Utah Rating Scale may be helpful in diagnosing ADHD in adults.

o The Continuous Performance Tests (CPTs) are computer-based tasks that often are us
conjunction with clinical information to make a diagnosis. A currently popular example i
While these tests can be supportive of the diagnosis in a full clinical evaluation, they ha
not be the sole basis for diagnosis.

Vision and hearing should be checked.

 TREATMENT
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Medical Care: Recent data suggest that carefully crafted stimulant therapy is more effective than be
(medication management by pediatricians). For related areas of functioning, such as social skills and
combined with behavioral treatments may be indicated. Pharmacotherapy includes the following:

Stimulants (methylphenidate, dextroamphetamine)

o These are first-line therapy and probably the most effective treatment.
o All stimulants have similar efficacy but differ by dosing, duration of action, and adverse
should be made to start at the lowest dose and titrate up for clinical efficacy or to intole
o Targeted symptoms include impulsivity, distractibility, poor task adherence, hyperactivit
o Some stimulants come in sustained-release preparations, which may decrease the num
should be spaced every 4-6 hours.

o Care should be taken to not dose too close to bedtime because stimulants may cause
o Other common adverse effects include appetite suppression and weight loss, headach
o Stimulants may exacerbate tics in children with underlying tic disorders.
o Whether growth might be affected while a child is taking stimulants remains unclear. D
weekends) may or may not be recommended to allow periods of normal growth. The d
chart and behavior and cognition off medication.

Atomoxetine (Strattera) has become a second-line and, in some cases, first-line treatment in
deficit/hyperactivity disorder (ADHD) because of its efficacy and classification as a nonstimula
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 th
Tricyclic antidepressants (imipramine, desipramine, nortriptyline) have been found effective in
however, because of potential adverse effects, they are rarely used for this purpose. If these a
because these agents can affect cardiac conduction. A few reports have described sudden de
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
with methylphenidate at bedtime. Again, the etiology of these deaths is unclear, and this rema
Modafinil (Provigil) has recent placebo-controlled data supporting its efficacy in children with A
used as a third- or fourth-line treatment.
Magnesium pemoline (Cylert) had been used in the 1990s, but concerns of rare, potentially fa
medication.
Behavioral psychotherapy often is effective when used in combination with an effective medic

o Working with parents and schools to ensure environments conducive to focus and atte
o Behavioral therapy or modification programs can help diminish uncertain expectations

o For adults with ADHD, working to establish ways of decreasing distractions and improv

Diet:
 For decades, speculation and folklore have suggested that foods containing preservatives or
may exacerbate ADHD. Many controlled studies have examined this question. To date, no ad
speculation.

MEDICATION
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Although pediatricians, parents, and teachers have hoped for effective therapies and methods that d
attention-deficit/hyperactivity disorder (ADHD), evidence to date supports that the specific symptoms
medication. Perhaps the mildest cases of ADHD can be treated with moderate success with environm
but other than these limited situations, pharmacotherapy often is needed.

Drug Category: Stimulants -- These agents are known to treat ADHD effectively.

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

Drug Name approved by FDA for ADHD in children aged 6 y or older. Most comm
used drug. Available in sustained-release forms.
5 mg/d PO in am or divided bid; not to exceed 60 mg/d (stated in
Adult Dose Physicians Desk Reference, but some selected individuals benefit fr
somewhat higher dose without apparent adverse reactions)
Pediatric Dose 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 d
that is known as acceptable for patient)
Documented hypersensitivity; glaucoma, Tourette syndrome, motor
patients with agitation, tension, and anxiety; untreated hypertension
Contraindications untreated glaucoma; substance abuse may be a relative contraindic
in some patients (patients with untreated ADHD have higher rates o
substance abuse than those treated for ADHD)
Reduces effects of guanethidine and bretylium; toxicity of phenytoin
Interactions tricyclic antidepressants, warfarin, primidone, and phenobarbital ma
increase when administered concurrently; MAOIs increase toxicity
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Caution in dementia, seizures, and hypertension; potentially addictiv
Dexmethylphenidate (Focalin, Focalin XR) -- Contains the more
pharmacologically active d-enantiomer of racemic methylphenidate.
Blocks norepinephrine and dopamine reuptake into presynaptic neu
Drug Name
and increases release of these monamines into extraneuronal spac
allow once-daily dosing, each extended-release (XR) cap contains h
dose as immediate-release and half as enteric-coated, delayed-rele
Focalin: 2.5 mg PO bid (if not currently taking racemic methylphenid
patient currently taking dexmethylphenidate, initiate dose at half tha
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 afte
Adult Dose if warranted; not to exceed 20 mg/d

Focalin XR (currently taking dexmethylphenidate [Focalin]): Adminis

same total daily dose as Focalin but administer qd

Focalin XR (currently taking racemic methylphenidate): Switch to ha

daily dose and administer qd; not to exceed 20 mg/d
Pediatric Dose <6 years: Not established
>6 years:
Focalin: 2.5 PO bid initially, may increase in 2.5- to 5-mg increments
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 increme
qwk if warranted; not to exceed 20 mg/d
Focalin XR (currently taking dexmethylphenidate [Focalin]): Adminis
same total daily dose as Focalin but administer qd
Focalin XR (currently taking racemic methylphenidate): Switch to ha
 daily dose and administer qd; not to exceed 20 mg/d
Documented hypersensitivity to dexmethylphenidate or methylphen
marked anxiety, tension, or agitation; glaucoma; motor tics or Touret
Contraindications
syndrome; coadministration with MAOIs or within 14 d following
discontinuation of MAOIs
Coadministration with MAOIs or within 14 d following discontinuation
MAOIs may result in hypertensive crisis and is contraindicated;
coadministration with other vasopressors (eg, pseudoephedrine) ma
increase blood pressure; may counteract effect of antihypertensive
Interactions
may inhibit metabolism of warfarin, anticonvulsants (eg, phenobarbi
phenytoin, primidone), and TCAs (eg, imipramine, clomipramine,
desipramine); serious adverse events reported with concomitant clo
although no causality established
Pregnancy C - Safety for use during pregnancy has not been established.
Not intended to treat severe depression or fatigue states; may exac
psychosis; may lower seizure threshold in patients with prior history
EEG abnormalities; may cause visual disturbances and increase blo
pressure; caution with history of drug dependence or alcoholism; mo
Precautions CBC count, differential, and platelet count periodically with prolonge
therapy; common adverse effects include nervousness, insomnia,
decreased appetite, abdominal pain, and weight loss; XR formulatio
be swallowed whole or sprinkled on a spoonful of applesauce (do no
crush, chew, or divide)
Magnesium pemoline (Cylert) -- Less frequently used because of ra
potential hepatotoxic effects and slower onset of action.
The United States Food and Drug Administration (FDA) conclud
that the overall risk of liver toxicity from pemoline outweighs th
Drug Name
benefits. In May 2005, Abbott chose to stop sales and marketin
their brand of pemoline (Cylert) in the U.S. In October 2005, all
companies that produced generic versions of pemoline also ag
to stop sales and marketing of pemoline.
Adult Dose 37.5-112.5 mg/d PO
<6 years: Not established
Pediatric Dose
>6 years: Administer as in adults
Contraindications Documented hypersensitivity; hepatic dysfunction
Interactions None reported
Pregnancy C - Safety for use during pregnancy has not been established.
Caution in patients with renal insufficiency; perform liver function tes
Precautions
prior to and during therapy
Drug Name Dextroamphetamine and amphetamine mixtures (Adderall) -- Produ
CNS and respiratory stimulation. The CNS effect may occur in the
cerebral cortex and reticular activating system. May have direct effe
 both alpha- and beta-receptor sites in the peripheral system as well
release stores of norepinephrine in adrenergic nerve terminals.
Mixture contains various salts of amphetamine and dextroamphetam
Available as 5-, 7.5-, 10-, 12.5-, 15-, 20-, and 30-mg scored tablets.
Adult Dose 5-60 mg/d PO divided bid/tid
<3 years: Not established
3-6 years: 2.5 mg/d PO initially; increase by 2.5 mg qwk
Pediatric Dose
>6 years: 5 mg/d PO or divided bid initially; increase by 5 mg qwk; n
exceed 40 mg/d
Documented hypersensitivity; hypertension; advanced arteriosclero
Contraindications hyperthyroidism; glaucoma; agitated states; within 14 d of MAOIs
administration
Coadministration with MAOIs may precipitate hypertensive crisis;
anesthetics may precipitate arrhythmias; dextroamphetamine may
Interactions
increase toxicity of phenobarbital, propoxyphene, meperidine, TCAs
phenytoin, and norepinephrine
Pregnancy C - Safety for use during pregnancy has not been established.
Caution in nephritis, hypertension, angina, glaucoma, cardiovascula
Precautions
disease, psychopathic personalities, or history of drug abuse
Atomoxetine (Strattera) -- Elicits selective inhibition of the presynap
Drug Name
norepinephrine transporter. Used to improve symptoms of ADHD.
40 mg/d PO initially; after 3 d, increase up to 80 mg/d PO or divided
Adult Dose (morning and late afternoon); may increase dose further after 2-4 w
to exceed 100 mg/d
<70 kg: 0.5 mg/kg/d PO initially; after 3 d, increase to 1.2 mg/kg/d P
divided bid (morning and late afternoon); not to exceed 1.4 mg/kg/d
Pediatric Dose
mg/d (whichever is less)
>70 kg: Administer as in adults
Documented hypersensitivity; do not use MAOIs within 2 wk; narrow
Contraindications
glaucoma
Eliminated primarily via CYP450 2D6 isoenzyme (thus, enzyme inhi
[eg, fluoxetine, paroxetine, quinidine] may increase atomoxetine lev
Interactions
coadministration with vasopressors may increase HR and BP; do no
within 2 wk of MAOIs
Pregnancy C - Safety for use during pregnancy has not been established.
Decrease dose with moderate-to-severe hepatic dysfunction; rare a
reactions (eg, angioneurotic edema, urticaria, rash) have been repo
caution in patients with hypertension, tachycardia, or cardiovascular
Precautions
cerebrovascular disease; may increase BP or HR; may cause urina
hesitancy or orthostatic hypotension; monitor growth (may decrease
weight)
 Dextroamphetamine (Dexedrine) -- Commonly used first or in case
methylphenidate failure. Approved by FDA for use in children aged 3
Drug Name
older. Available in sustained-release forms, which may allow for dail
dosing.
Initial: 5 mg/d PO; not to exceed 40 mg/d (as listed in the Physician
Adult Dose Reference); some selected patients may benefit from a slightly high
dose without adverse reaction
Pediatric Dose >6 years: 2.5 mg/d PO; may titrate up by 2.5 mg/d once or twice we
Documented hypersensitivity; hypertension; MAOIs; advanced
arteriosclerosis; hyperthyroidism; glaucoma; substance abuse may
Contraindications
relative contraindication is some patients (patients with untreated AD
have higher rates of substance abuse than those treated for ADHD)
Coadministration with MAOIs may precipitate hypertensive crisis an
anesthetics may precipitate arrhythmias; may increase toxicity of
Interactions
phenobarbital, propoxyphene, meperidine, tricyclic antidepressants,
phenytoin, and norepinephrine
Pregnancy C - Safety for use during pregnancy has not been established.
Caution in angina, glaucoma, cardiovascular disease, and psychopa
Precautions
personalities; potentially addictive

Drug Category: Atypical antidepressants -- Recent studies support efficacy of venlafaxine and bupro
action than stimulants but potentially fewer adverse effects.

Bupropion (Wellbutrin) -- Inhibits neuronal dopamine reuptake in ad

Drug Name to being a weak blocker of serotonin and norepinephrine reuptake. A
available in sustained-release preparations (Wellbutrin SR)
75 mg/d PO or 100 mg/d SR PO, initially; if initial dose ineffective an
Adult Dose higher dose tolerated, increase gradually to maximum 150 mg tid or
mg SR bid
Pediatric Dose Not established, but often used "off label"
Documented hypersensitivity; seizure disorder; anorexia nervosa;
Contraindications
concurrent use with MAOIs
Carbamazepine, cimetidine, phenytoin, and phenobarbital may decr
Interactions effects; toxicity increases with concurrent administration of levodopa
MAOIs
Pregnancy C - Safety for use during pregnancy has not been established.
Doses >400 mg/d of SR preparation or 450 mg/d of immediate-relea
Precautions preparation associated with higher incidence of seizure; caution in p
with renal or hepatic insufficiency
Drug Name Venlafaxine (Effexor) -- May inhibit neuronal serotonin and norepine
reuptake. In addition, causes beta-receptor downregulation. Availab
 sustained-release preparations (Effexor XR)
25 mg/d PO initially and increase as tolerated to 75-375 mg/d PO di
Adult Dose
into bid dosing regimen
Pediatric Dose Not established
Documented hypersensitivity; patients taking MAOIs or who have ta
Contraindications them within 14 d of initiating therapy; uncontrolled hypertension (ma
cause slight increase in blood pressure at higher doses)
Cimetidine, MAOIs, sertraline, fluoxetine class I-C antiarrhythmics, t
Interactions
antidepressants, and phenothiazine may increase effects
Pregnancy C - Safety for use during pregnancy has not been established.
Patients may experience hypertension; fatal reaction may occur if ta
concurrently with an MAOI; exercise caution in patients with
Precautions
cardiovascular disorders; may be associated with increased blood
pressure at higher doses

Drug Category: Tricyclic antidepressants -- See article entitled Depression. Patients may require l
onset of action.

Imipramine (Tofranil) -- Inhibits the reuptake of norepinephrine or se

Drug Name (5-hydroxytryptamine, 5-HT) at presynaptic neuron. May be useful in
pediatric ADHD.
Adult Dose Not established
Initial: 10 mg/d PO; if tolerated and not effective, increase to 25 mg/
Pediatric Dose titrate upward slowly by 25 mg/wk to effectiveness or intolerable adv
effects
Problems of slowed or irregular cardiac conduction; untreated glauc
Contraindications
recent or concurrent MAOIs
Increases toxicity of sympathomimetic agents such as isoproterenol
Interactions epinephrine by potentiating effects and inhibiting antihypertensive e
of clonidine
Pregnancy C - Safety for use during pregnancy has not been established.
Overdose may be lethal; may impair mental or physical abilities requ
for performance of potentially hazardous tasks; caution in patients w
Precautions cardiovascular disease, conduction disturbances, seizure disorders,
urinary retention, hyperthyroidism, or those receiving thyroid replace
therapy

Drug Category: Alpha-adrenergic agonists -- Centrally acting antihypertensives clonidine and guanf
ADHD. Inhibition of norepinephrine release in brain may be mechanism of action.

Drug Name Clonidine (Catapres) -- Not approved by FDA for any psychiatric use
 children. However, may be effective in ADHD. Available in tabs or
transdermal skin patches.
Adult Dose 0.1-0.3 mg PO divided bid/tid
Pediatric Dose Not established
Documented hypersensitivity; cardiovascular disease; depressive
Contraindications
symptoms
Concurrent CNS depressants may increase effects; tricyclic
Interactions antidepressants may decrease levels; sudden death reported in pat
taking clonidine with methylphenidate at bedtime
Pregnancy D - Unsafe in pregnancy
Caution in cerebrovascular disease, coronary insufficiency, sinus no
Precautions
dysfunction, and renal impairment
Guanfacine (Tenex) -- Has similar mechanism of action to clonidine
Drug Name has longer half-life and may be less sedative. Not recommended for
children <12 y.
Adult Dose 1-3 mg PO divided bid/tid
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Increases effect of other hypotensive agents; tricyclic antidepressan
Interactions
decrease hypotensive effects
Pregnancy B - Usually safe but benefits must outweigh the risks.
Caution in hepatic impairment, severe coronary insufficiency, and re
Precautions
myocardial infarction
FOLLOW-UP
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Further Outpatient Care:

Regular follow-up is needed long-term for patients with attention-deficit/hyperactivity disorder

ADHD is not an illness for which one can hand the patient a prescription for pills and assume

Prognosis:

Childhood ADHD may confer a higher risk of diagnosis with conduct disorders and substance
These may be primary coexisting disorders or disorders secondary to untreated or undertreat

Most children with ADHD have relatively good psychiatric outcomes once they reach adulthoo

At least 15-20% continue to have full ADHD as adults, and as many as 65% may continue to
interfere with full realization of academic or work potential.
Patient Education:

The educational requirements of these patients and their family members are high. Family me
children, spouses and children of adults, and grown children of elderly patients. Encourageme
structuring and behavioral control, social skill training, and frequent cognitive redirecting is ne

For excellent patient education resources, visit eMedicine's Mental Health and Behavior Cent
article Attention-Deficit/Hyperactivity Disorder.

MISCELLANEOUS
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Medical/Legal Pitfalls:

If the medications used are schedule-II controlled substances (d-amphetamine, methylphenid

travel with them in their original pharmacy bottle.

The event of a stimulant-abusing individual presenting with a complaint of attention-deficit/hyp

substances to abuse is surprisingly rare. It does occur, however, so remain alert for the possib

Special Concerns:

ADHD can be comorbid with the following conditions:

o Other developmental learning disorders

o Conduct disorder or oppositional defiant disorder

o Bipolar disorder

o Tourette syndrome

o Pervasive developmental disorder

o Mental retardation

When evaluating a patient with any of these disorders, special care should also be made to e
bipolar disorder, is readily treatable.

ADHD is a heterogeneic disorder that carries significant comorbidity. Symptoms consistent wi

these signs and symptoms could be a precursor in childhood to later disorders such as bipola

BIBLIOGRAPHY
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography
 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders (DSM
Psychiatric Association; 2000. 78-85.
Baving L, Laucht M, Schmidt MH: Atypical frontal brain activation in ADHD: preschool and ele
Child Adolesc Psychiatry 1999 Nov; 38(11): 1363-71[Medline].
Biederman J, Faraone S, Milberger S: A prospective 4-year follow-up study of attention-deficit
Gen Psychiatry 1996 May; 53(5): 437-46[Medline].
Biederman J, Faraone SV, Milberger S: Is childhood oppositional defiant disorder a precursor
from a four-year follow-up study of children with ADHD. J Am Acad Child Adolesc Psychiatry 1
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