General Information (including ICD-9/-10 Codes)

Description :

  • childhood disorder, disruptive behavior disorder

Also called :

  • attention-deficit disorder (ADD), hyperkinetic syndrome, hyperkinetic impulse disorder, minimal brain damage/dysfunction

ICD-9 Codes :

  • 314.0 attention deficit disorder of childhood
    • 314.00 attention deficit disorder of childhood without mention of hyperactivity
    • 314.01 attention deficit disorder of childhood with hyperactivity
  • 314.1 hyperkinesis of childhood with developmental delay
  • 314.2 hyperkinetic conduct disorder of childhood
  • 314.8 other specified manifestations of hyperkinetic syndrome of childhood
  • 314.9 unspecified hyperkinetic syndrome of childhood

ICD-10 Codes :

  • F90.0 disturbance of activity and attention
  • F90.1 hyperkinetic conduct disorder
  • F90.8 other hyperkinetic disorders
  • F90.9 hyperkinetic disorder, unspecified
  • F98.8 other specified behavioural and emotional disorders with onset usually occurring in childhood and adolescence [used for attention deficit disorder without hyperactivity]

Who is most affected :

  • children, onset < 7 years old
  • boys 10x (probably overdiagnosed in boys, underdiagnosed in girls)
  • 3-9% at age 7-9, 1-2% teenagers (due to compensating skills)

Incidence/Prevalence :

  • #1 behavioral disorder of school-age children
  • 6.8% prevalence among school-aged children ages 6-12 years
    • based on systematic review of 14 studies
    • prevalences ranged from 4.2% to 26%
    • pooled prevalence estimates were 6.8% using DSM-III criteria, 10.3% using DSM-III-R criteria, and 6.8% in single study using DSM-IV criteria
    • prevalence 3 times higher for boys (9.2% vs. 3%) than girls, but did not vary with age
    • Reference - AHRQ evidence-based review (Evid Rep Technol Assess (Summ) 1999 Nov;(11):i-viii, 1-341)
  • 5.4% to 16% prevalence rates in children reported in subsequent studies in United States
    • 5.44% prevalence among 9,278 US children (mostly third graders) based on parental report of professional diagnosed ADHD
      • characteristics associated with lower rate of ADHD diagnosis were girls, black children, Hispanic children, living with biological father, western region of United States, and having white teacher
      • characteristics associated with higher rate of ADHD diagnosis were having older teacher and stricter state-level performance accountability laws
      • Reference - Pediatrics 2006 Apr;117(4):e601
    • 7.8% US children ages 4-17 years had ever had ADHD diagnosed, based on parental surveys of 102,353 children in 2003, 4.3% (56% of those with ADHD diagnosis) were taking medication for ADHD (MMWR 2005 Sep 2;54(34):842); 10.3% boys and 4% girls ages 5-17 years in US had ever had ADHD diagnosed (MMWR 2005 Nov 4;54(43):1107), summary can be found in Am Fam Physician 2006 Feb 15;73(4):730
    • lifetime prevalence estimates range from 7.5% to 16% during childhood; population-based birth cohort study followed 5,718 children for 19 years, 7.5% had definite ADHD (clinical diagnosis and supporting school or parent documentation); 9% had definite or probable ADHD (clinical diagnosis with or without documentation); 16% had definite, probable or questionable ADHD (clinical diagnosis OR documentation) (Arch Pediatr Adolesc Med 2002 Mar;156(3):217 in Pediatric Notes 2002 Apr 4;26(14):53 + in J Watch 2002 May 1;22(9):72)
    • 8.7% prevalence of ADHD by DSM-IV criteria in children aged 8-15 years in survey of 3,082 children in United States from 2001-2004 (Arch Pediatr Adolesc Med 2007 Sep;161(9):857) (* further peer review in progress)
  • cumulative incidence up to 2.69% at age 8 years in Taiwan
    • based on national data with 1,70,966 children born 1996-2001 and evaluated in 2004 based on database records, follow-up 3-8 years based on birth cohort
    • cumulative incidence of ADHD 0.55% at 3 years, 0.98% at 4 years, 1.52% at 5 years, 2.15% at 6 years, 2.59% at 7 years and 2.69% at 8 years
    • Reference - Pediatrics 2007 Feb;119(2):e435
  • cumulative incidence up to 0.42% at age 11 years in Denmark
    • based on national registries with all 669,995 children born in Denmark 1990-1999
    • cumulative incidence of hyperkinetic disorder per 10,000 children at selected ages
      • 0.4 to 0.6 at age 3 years
      • 2.3 to 7 at age 5 years, increasing from 1992 to 1999 birth cohorts
      • 10.4 to 20.2 at age 7 years, increasing from 1992 to 1997 birth cohorts
      • 24.7 to 35.2 at age 9 years, increasing from 1992 to 1995 birth cohorts
      • 42.2 at age 11 years, based on 1992-1993 birth cohort
    • Reference - Arch Pediatr Adolesc Med 2007 Feb;161(2):193
  • incidence of ADHD in children having a parent who is similarly affected is 1 in 4 (JAMA 1995 Jun 21;273(23):1871 in QuickScan Reviews in Fam Pract 1995 Dec:2)
  • prevalence varies from 1.7-16% in different studies with most commonly accepted ranges of 3-6% children (JAMA 1998 Apr 8;279(14):1100 in QuickScan Reviews in Fam Pract 1998 Oct;23(7):18)
  • little evidence of widespread overdiagnosis or misdiagnosis of ADHD or of widespread overprescription of methylphenidate by physicians (JAMA 1998 Apr 8;279(14):1100) (* further peer review in progress)

Causes and Risk Factors

Causes :

  • unknown, not a primary behavior problem

Pathogenesis :

  • current theory is dysfunction of prefrontal and subcortical striatal areas of brain that are implicated in inhibition of irrelevant responses and executive functions (Arch Gen Psychiatry 1996 Jul;53(7):607 in BMJ 1997 Oct 11;315(7113):894)
  • cortical brain size in ADHD patients reduced in inferior portions of dorsal prefrontal cortices and anterior temporal cortices bilaterally, and increased in posterior temporal and inferior parietal cortices bilaterally, based on MRI study of 27 children and adolescents with ADHD and 46 matched controls (Lancet 2003 Nov 22;362(9397):1699)
  • molecular genetic study suggests possible relation with D4 receptor gene (Molecular Psychiatry 1996 May;1(2):121 in BMJ 1997 Oct 11;315(7113):894)
  • possible phentoypic variation in catechol O-methyltransferase gene (COMT) in children with ADHD
  • intrinsic deficiency or dysregulation of dopamine and norepinephrine, causing dysregulation of cortical activities, especially in frontal lobe (Psychiatric Annals 1997 Aug;27(8):545)

Likely risk factors :

  • first-born boys
  • monozygotic twins > dizygotic twins
  • parents with hyperkinesis, sociopathy, alcoholism, conversion disorder

Possible risk factors :

  • prenatal smoking; 140 boys with ADHD compared with 120 controls, 22% vs. 8% mothers reported prenatal smoking; smoking also associated with lower children's IQs by an average 10 points (Am J Psychiatry 1996 Sep;153(9):1138 in J Watch Women's Health 1996 Oct;1(7):54)
  • ADHD associated with prenatal exposure to alcohol (odds ratio 2.5) and cigarettes (odds ratio 2.1) in case-control study with 522 subjects, retrospective study may have high chance of recall bias (J Am Acad Child Adolesc Psychiatry 2002 Apr;41(4):378 in Pediatric Notes 2002 Apr 11;26(15):60)
  • premature birth may be associated with ADHD
    • systematic review of cognitive and behavioral outcomes of children born preterm identified 15 studies comparing 1,556 cases vs. 1,720 controls with evaluations performed after age 5 years
    • 6 studies addressed ADHD outcomes, preterm-born children had 2.64 times risk for developing ADHD
    • results not affected by study quality in separate analyses of high-quality and low-quality studies
    • Reference - JAMA 2002 Aug 14;288(6):728
    • preterm birth and low birth weight associated with hyperkinetic disorder in case-control study with 834 cases and 20,100 controls (Arch Dis Child 2006 Aug;91(8):655)
  • hours of television viewing at age 1-3 years modestly associated with risk of attentional problems at age 7 years in prospective study of 1,345 children (Pediatrics 2004 Apr;113(4):708), editorial can be found in Pediatrics 2004 Apr;113(4):917, commentary can be found in Pediatrics 2004 Aug;114(2):511, commentary can be found in Pediatrics 2004 Nov;114(5):1372
  • food additives  might promote hyperactivity in children, but evidence limited and inconsistent
  • Turner syndrome; ADHD found in 12 (24%) of 50 girls with Turner syndrome (J Pediatr Psychol 2006 Oct;31(9):945)

Factors not associated with increased risk :

  • sugar intake does NOT affect behavior or cognitive performance

Complications and Associated Conditions

Complications :

  • delinquency, antisocial personality disorder, substance abuse in adulthood
  • ADHD associated with increased risk for substance abuse
    • ADHD associated with increased risk of drug use, as is "externalizing behavior problems" (aggressiveness, acting out, disruptive behaviors, conduct disorder, oppositional defiant disorder); psychostimulant use not associated with drug use, low parent monitoring and high peer drug use associated with increased drug use; based on study of 717 children evaluated at age 6 years and at age 11 years (J Am Acad Child Adolesc Psychiatry 1999 Nov;38(11):1347 in Pediatric Notes 1999 Nov 25;23(47):185)
    • untreated ADHD associated with increased risk for substance use disorder in adolescence, pharmacotherapy associated with 85% reduction in risk for substance use disorder; based on study of cumulative incidence of substance use disorder throughout adolescence compared in 56 medicated boys with ADHD (25% incidence of substance use disorder), 19 nonmedicated boys with ADHD (75% incidence), and 137 non-ADHD boys (18% incidence); study subjects were highly selected which may introduce bias (Pediatrics 1999 Aug;104(2):e20 full-text)
    • earlier initiation of smoking (J Am Acad Child Adolesc Psychiatry 1997 Jan;36(1):37 in Pediatric Notes 1997 Jan 16;21(3):10)
  • driving impairments
    • unmedicated ADHD patients have increased risk for having citations for speeding, suspended driving licenses, crashes and crashes causing bodily injury; based on study comparing 25 unmedicated young adults with ADHD with 23 young adults without ADHD (Pediatrics 1996 Dec;98(6 Pt 1):1089 in QuickScan Reviews in Fam Pract 1997 May;22(2):22)
    • adults with ADHD more likely than controls to collide with obstacle suddenly appearing from periphery during low stimulus setting in driving simulation (65% vs. 29%) in study comparing 20 adults with ADHD and 21 controls (Ann Gen Psychiatry 2007 Jan 30;6:4 full-text)
  • children with ADHD have comparable physical health but poorer health-related quality of life on all domains of psychosocial health, based on study of 131 children with ADHD (Pediatrics 2004 Nov;114(5):e541 full-text)

Associated conditions :

  • up to 50% learning disabilities
  • comorbid psychiatric conditions reported in 53 of 121 (44%) children ages 6-17 years with ADHD in a pediatric psychiatric referral population including 35 (29%) with multiple anxiety disorder, 18 (15%) with conduct disorder, 18 (15%) with major depression, and 8 (7%) with bipolar disorder (Arch Dis Child 2005 Oct;90(10):1010 in Pediatric Notes 2005 Nov 10;29(45):177)
  • conduct disorder, oppositional defiant disorder (more common than conduct disorder), specific developmental disorder, anxiety disorder, affective disorder (demoralized, 30% depression in teenagers), mental retardation, autism, Tourette's disorder (motor and vocal tic at 9-10)
  • occasionally epicanthal folds, hypertelorism, low-set or malformed ears, high-arched palate, clinodactyly (inward curvature) of 5th finger
  • increased incidence of traffic offenses and traffic accidents in New Zealand study of ages 15-18 years (J Am Acad Child Adolesc Psychiatry 1997 Apr;36(4):515 in Pediatric Notes 1997 Apr 24;21(17):67)
  • association with enuresis controversial
    • ADHD and enuresis associated; based on questionnaires from 153 parents of ADHD patients and 142 parents of controls; children with ADHD 2.7 times more likely to have nocturnal enuresis and 4.5 times more likely to have diurnal enuresis (South Med J 1997 May;90(5):503 in QuickScan Reviews in Fam Pract 1997 Nov;22(8):14)
    • ADHD and primary nocturnal enuresis not associated, i.e. have patterns of inheritance consistent with independent transmission (Acta Paediatr 1999 Dec;88(12):1364 in Pediatric Notes 2000 Jan 6;24(1):4)
  • attention-deficit/hyperactivity disorder (ADHD) may be associated with increased risk of unprovoked seizures; population-based case-control study in Iceland compared all children ages 3-16 years with newly diagnosed unprovoked seizures with matched controls (the next 2 same-sex births in population registry); history of ADHD was 2.5-fold more common in cases than controls, association statistically significant only for ADHD predominantly inattentive type (Arch Gen Psychiatry 2004 Jul;61(7):731 in JAMA 2004 Oct 13;292(14):1664)
  • growth abnormality
    • ADHD may be associated with higher level of prepubertal growth and earlier onset of growth spurt in stimulant-naive boys (* further peer review in progress)
      • based on retrospective cohort
      • growth data from 53 children and adolescents aged 6-17 years (48 boys) with ADHD were assessed
      • participants had never been medicated with stimulants
      • 0.33 cm/year higher velocity of growth of boys in the prepubertal stage (p = 0.001)
      • 5 months earlier onset of growth spurt (p = 0.002)
      • distinct suppression of growth was reported to be found in boys aged 9-14 years
      • Reference - Pediatrics 2008 Apr;121(4):e967, commentary can be found in Pediatrics 2008 Jul;122(1):221
    • ADHD may be associated with temporary deficits in height gain through midadolescence that may normalize by late adolescence
      • review of controlled study in 124 boys with ADHD
      • found small but significant differences in height early but not late in adolescence between children with and without ADHD
      • height deficits not related to psychotropic medications
      • Reference - Pediatrics 1998 Aug;102(2 Suppl):501
  • sleep problems reported to be common in children with ADHD
    • based on cross-sectional survey
    • 330 caregivers of a schoolage child with ADHD surveyed about child's sleep problems
    • 239 (74%) caregivers completed survey
    • mild sleep problems in 28.5%
    • moderate or severe sleep problems in 44.8%
    • Reference - Arch Pediatr Adolesc Med 2008 Apr;162(4):336

History

Chief Concern (CC) :

  • short attention span, impulsivity, hyperactivity, inattention or school problem
  • other symptoms in adult ADHD - compulsive eating, insomnia, restlessness during sleep

History of Present Illness (HPI) :

  • girls tend to have inattention, then depression in adulthood
  • boys tend to be hyperactive, aggressive, later oppositional
  • behavior rating scales helpful but cannot replace careful history
  • ADHD unlikely unless parental concerns or teacher concerns about hyperactivity
    • survey of 10,438 children ages 5-15 years in Great Britain
    • 2.2% had ADHD based on DSM-IV criteria
    • negative predictive values are percentages without a disorder (ADHD in this case) if informant(s) do(es) not express concern
    • 3.4% had parental report of hyperactivity which had 35% sensitivity, 97.3% specificity, 23% positive predictive value and 98.5% negative predictive value for ADHD
    • 3.7% had parental report of teacher concern about hyperactivity which had 58% sensitivity, 97.6% specificity, 35% positive predictive value and 99% negative predictive value for ADHD
    • 0.8% had parental report of hyperactivity and teacher concern about hyperactivity which had 23% sensitivity, 99.7% specificity, 62% positive predictive value and 98.3% negative predictive value for ADHD
    • Reference - BMJ 2005 Dec 17;351(7530):1435 full-text
  • ADHD toolkit, including parent and teacher rating scales, can be found at National Initiative for Children's Healthcare Quality (NICHQ)

Past Medical History (PMH) :

  • perinatal history
  • adults do not always remember having ADHD symptoms during childhood; in one study, only 60% of adults diagnosed as children recalled the diagnosis (Arch Gen Psychiatry 1995 Jun;52(6):429 in QuickScan Reviews in Fam Pract 1996 Jan:20)

Family History (FH) :

  • 40% have relative with ADHD

Social History (SH) :

  • wants to keep rules, just can't manage, poor judgment, early temperament
  • preschool and school history
  • maternal ratings of child behavior improve with treatment of maternal depression; study of 24 women with major depressive disorder evaluated before and 1-2 months after antidepressant treatment, improvements in Conners' Parent Rating Scale of child behavior correlated with maternal improvements in Beck Depression Inventory; most of reported behavioral changes were in conduct, learning problem and impulsive-hyperactive areas (Fam Med 2001 Oct;33(9):691)
  • food additives might promote hyperactivity
    • artificial food colors might promote hyperactivity in children with ADHD (level 2 [mid-level] evidence)
    • food additives do not clearly affect hyperactivity (level 2 [mid-level] evidence)
      • based on randomized crossover trial with high dropout rate
      • 397 children age 3 years randomized to fruit juice with food additives vs. fruit juice alone (placebo) for 1 week each in crossover trial preceded by and separated by 1-week no-fruit-juice no-food-additive washout periods
      • 277 completed the trial
      • no differences between food additive and placebo states in terms of hyperactivity or atopy by parent or researcher ratings
      • washout periods had less hyperactive behavior by parent ratings (not statistically significant) but no differences in atopy or researcher ratings
      • Reference - Arch Dis Child 2004 Jun;89(6):506 in CMAJ 2004 Aug 31;171(5):450), editorial can be found in Lancet 2004 Sep 4-10;364(9437):823, commentary can be found in Am Fam Physician 2004 Oct 15;70(8):1551
    • artificial colors and/or sodium benzoate might increase hyperactivity in children in general population (level 2 [mid-level] evidence)
      • based on randomized trial with borderline statistical significance
      • 153 children aged 3-4 years and 144 children aged 8-9 years in Southampton, UK were randomized in crossover trial over 6 weeks with artificial colors and sodium benzoate withdrawn from diet
        • week 0 was typical diet (baseline diet)
        • week 1 was withdrawal diet plus placebo drink
        • week 2 was randomized assignment to drink A, drink B or placebo drink
        • week 3 was washout period with placebo drink
        • week 4 was randomized assignment
        • week 5 was washout period with placebo drink
        • week 6 was randomized assignment
      • 3-year-old children consumed 300 mL/day of mixed fruit juices
        • drink A contained 20 mg of artificial food colorings and 45 mg of sodium benzoate
        • drink B contained 30 mg of artificial food colorings and 45 mg of sodium benzoate
      • 8/9-year-old children consumed 625 mL/day of mixed fruit juices
        • drink A contained 24.98 mg of artificial food colorings and 45 mg of sodium benzoate
        • drink B contained 62.4 mg of artificial food colorings and 45 mg of sodium benzoate
      • 137 (89.5%) children aged 3-4 years and 130 (90%) children aged 8-9 years completed the trial
      • primary outcome was global hyperactivity aggregate (GHA) which was composite of abbreviated teacher rating, parent rating, direct classroom observation, and (for children aged 8-9 years) computerized continuous performance test
      • results not reported for specific ratings, results only reported for GHA
      • estimated marginal means for GHA were lower with placebo than with either study drink
        • difference with drink A in 3-year-olds only reached statistical significance in subgroup with ≥ 85% consumption
        • difference with drink B in 3-year-olds did not reach statistical significance
        • difference with drink A in 8/9-year-olds only reached statistical significance in subgroup with 100% consumption
        • difference with drink B in 8/9-year-olds statistically significant but confidence interval included minimal effects
      • Reference - Lancet 2007 Nov 3;370(9598):1560, correction can be found in Lancet Nov 3;370(9598):1542, editorial can be found in Lancet 2007 Nov 3;370(9598):1524, commentary can be found in BMJ 2008 May 24;336(7654):1144
      • re-analysis by European Food Safety Authority finds little evidence for effect and insufficient evidence to change acceptable daily intakes of food additives (European Food Safety Authority opinion 2008 Mar 7 PDF) (* further peer review in progress)
    • synthetic food colorings reported to be associated with hyperactivity (level 3 [lacking direct] evidence) (* further peer review in progress)
      • based on 2 of 8 highly selected patients
      • 55 children with suspected hyperactivity followed Feingold diet for 6 weeks
      • 40 (73%) had improved behavior
      • 26 (47%) remained improved on liberalized diet for 3-6 months
      • 14 had parents who claimed behavior cluster was associated with synthetic food coloring
      • 8 of these children had tartrazine 50 mg or carmoisine 50 mg daily for 2 weeks each with placebo lead-in and washout
      • 2 of these 8 children had behavioral pattern (extreme irritability, restlessness, sleep disturbance) associated with food coloring
      • Reference - Aust Paediatr J 1988 Apr;24(2):143
  • sugar challenges have not shown evidence of behavior problems in 12 double-blind placebo-controlled trials (Crit Rev Food Sci Nutr 1996 Jan;36(1-2):31) (* further peer review in progress)
  • neither sucrose, aspartame nor saccharin affected behavioral outcomes in "sensitive" children (* further peer review in progress)
    • based on controlled trial
    • 25 normal preschool children aged 3-5 years and 23 school-age children aged 6-10 years described by parents as sensitive to sugar were assigned to each of 3 diets for 3 weeks each
      • high sucrose diet with no artificial sweeteners
      • low sucrose diet with aspartame
      • low sucrose diet with saccharin
    • no significant differences between diets in any of 39 behavioral and cognitive variables in sugar-sensitive children
    • only 4 of 31 variables had significant differences in preschool children, and these differences were not consistent
    • Reference - N Engl J Med 1994 Feb 3;330(5):301

Review of Systems (ROS) :

  • neurologic symptoms, sleep problems, elimination (incidence of encopresis increased with ADHD)

Physical

General Physical :

  • check head circumference
  • observe child's behavior and parent-child interaction

HEENT :

  • check hearing and vision

Neuro :

  • check neurologic exam including soft signs
    • synkinesis (mirror movements)
    • dysdiadochokinesia (difficulty with rapid alternating movements)
    • choreiform movements of fingers

Diagnosis

Making the diagnosis :

  • DSM-IV-TR criteria
    • criteria met only if more frequent than normal for mental age
    • inattention or hyperactivity-impulsivity
      • inattention - at least 6 of 9 symptoms 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
        • often has difficulty sustaining attention in tasks or play activities
        • often does not seem to listen when spoken to directly
        • often does not follow through on instructions and fails to finish work (not due to oppositional behavior or failure to understand instructions)
        • often has difficulty organizing tasks and activities
        • often avoids, dislikes or is reluctant to engage in tasks that require sustained mental effort
        • often loses things necessary for tasks or activities
        • often easily distracted by extraneous stimuli
        • often forgetful in daily activities
      • hyperactivity-impulsivity - at least 6 of 9 symptoms for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:
        • often fidgets with hands or feet or squirms in seat
        • often leaves seat in situations in which remaining seated is expected
        • often runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults, subjective feelings of restlessness)
        • often has difficulty playing or engaging in leisure activities quietly
        • often "on the go" or acts as if "driven by a motor"
        • often talks excessively
        • often blurts out answers before other questions have been completed
        • often has difficulty awaiting turn
        • often interrupts or intrudes on others
    • onset (of some symptoms) before age of 7
    • some impairment from symptoms in 2 or more settings
    • clear evidence of impairment in functioning
  • short symptom checklist may distinguish children with and without ADHD
    • Swanson, Nolan and Pelham (SNAP) checklist has sensitivity and specificity > 94% compared to DSM-III-R criteria
    • DSM-IV SNAP checklist PDF and scoring PDF based on DSM-IV but not adequately evaluated
    • other rating scales evaluated did not perform as well
    • Reference - J Fam Pract 2004 May;53(5):412
  • no evidence available to support diagnostic criteria of onset of symptoms before age 7 years (J Acad Child Adolesc Psychiatry 1997 Sep;36(9):1204 in Pediatric Notes 1997 Sep 25;21(39):155), commentary can be found in J Am Acad Child Adolesc Psychiatry 1998 Apr;37(4):343 and in J Am Acad Child Adolesc Psychiatry 1998 Jun;37(6):569
  • recommendations from combined views of 6 experts (3 from US, 3 from Europe) that diagnosis should be made by direct observation of child at home and in classroom, diagnosis only provisional before age 5 years (Lancet 1998 Feb 7;351(9100):429 in Pediatric Notes 1998 Mar 5;22(10):38), commentary can be found in Lancet 1998 Feb 7;351(9100):387, commentary can be found in Lancet 1998 May 9;351(9113):1432
  • little evidence of widespread overdiagnosis or misdiagnosis of ADHD or of widespread overprescription of methylphenidate by physicians (JAMA 1998 Apr 8;279(14):1100), commentary can be found in JAMA 1999 Apr 28;281(16):1490

Rule out :

  • lack of structure and consistent parental discipline
  • age-appropriate activity
  • oppositional, malicious, or aggressive behavioral problems
  • sensory deficits, receptive language problems, other specific learning disabilities
  • oppositional defiant disorder, conduct disorder, adjustment disorder, depression, parent-child problems, mental retardation, pervasive developmental disorder, psychotic disorder
  • seizures (e.g. childhood absence epilepsy), Tourette's syndrome (40% begin with ADHD picture), chronic illness, traumatic brain injury, fetal drug effects (especially alcohol)
  • sleep disorders
    • hyperactivity and inattention associated with daytime sleepiness and habitual snoring in cross-sectional survey of 866 children 2-14 years old attending general pediatric clinics (Pediatrics 2002 Mar;109(3):449), commentary can be found in Pediatrics 2002 Oct;110(4):850
    • sleep disorder in adults (JAMA 1999 Mar 3;281(9):797)
  • maternal depression -- maternal ratings of child behavior improve with treatment of maternal depression; study of 24 women with major depressive disorder evaluated before and 1-2 months after antidepressant treatment, improvements in Conners' Parent Rating Scale of child behavior correlated with maternal improvements in Beck Depression Inventory; most of reported behavioral changes were in conduct, learning problem and impulsive-hyperactive areas (Fam Med 2001 Oct;33(9):691)

Testing to consider :

  • ADHD toolkit, including parent and teacher rating scales, can be found at National Initiative for Children's Healthcare Quality (NICHQ)
  • recommendations from guidelines
    • ADHD-specific questionnaires (e.g. Conners scale) superior to nonspecific questionnaires in differentiating children with ADHD from normal children, nonspecific questionnaires should not be used for diagnosis
    • other diagnostic tests (EEG, brain imaging, TSH) not recommended
    • guidelines developed by AAP, AAFP, American Academy of Child and Adolescent Psychiatry, Child Neurology Society, and Society for Pediatric Psychology
    • Reference - Pediatrics 2000 May;105(5):1158 in J Watch 2000 Jun 15;20(12):97
    • summary of supporting literature review can be found in Pediatrics 2001 Mar;107(3):e43 full-text
  • hemoglobin (Hb) or hematocrit (Hct) if suspecting anemia
  • lead (Pb) level or free erythrocyte protoporphyrin (FEP) if suspecting lead toxicity

Blood tests :

  • children with ADHD may have lower serum ferritin levels but clinical significance not established (level 3 [lacking direct] evidence)
    • 53 children with ADHD compared with 27 matched controls
    • mean serum ferritin levels 23 ng/mL vs. 44 ng/mL
    • 84% vs. 18% had serum ferritin < 30 ng/mL
    • serum ferritin level inversely correlated with ADHD symptom severity
    • no significant differences in serum iron, hemoglobin or hematocrit levels
    • Reference - Arch Pediatr Adolesc Med 2004 Dec;158(12):1113 in J Watch Online 2004 Dec 21
  • iron supplementation  may improve ADHD symptoms and severity in children with ADHD and low serum ferritin levels (level 2 [mid-level] evidence) (* further peer review in progress)

Other diagnostic testing :

  • computerized continuous performance tests (CPT) used in clinical diagnosis, but if CPT used in making diagnosis, 122 mistakes would occur in evaluating 500 clinic referrals; history of behavior derived from clinical interview considered gold standard for diagnosis of ADHD (Contemp Pediatr 1996 Nov;13:53 in QuickScan Reviews in Fam Pract 1997 May;22(2):4)

Prognosis

Prognosis :

  • 1/3 improve with age
  • about 80% of children with ADHD continue to exhibit problem behaviors through adolescence and into adulthood (J Dev Behav Pediatr 1995 Jun;16(3):192 in QuickScan Reviews in Fam Pract 1996 Jan;19)

Treatment

Treatment overview :

  • stimulant therapy
    • methylphenidate (e.g. Ritalin 1 mg/kg/day in divided doses)
      • reduces core symptoms of ADHD
      • superior to non-drug treatments
      • improved outcomes when added to behavioral interventions
      • may disrupt sleep and appetite
      • long-acting formulations (Metadate CD or Metadate ER twice daily, Concerta or Ritalin LA once daily) may avoid difficult highs and lows for child and family
    • dexamphetamine sulfate more effective than placebo, but clinical importance unclear
      • dextroamphetamine (Dexedrine, Adderall) 0.5 mg/kg/day in divided doses
      • long-acting amphetamine formulations (Dexedrine Spansules or Adderall XR once daily)
    • few, if any, differences among methylphenidate, dextroamphetamine, and pemoline in review of 23 trials
    • pemoline (Cylert) withdrawn from market due to risk of hepatotoxicity
  • clonidine more effective than placebo in reducing ADHD symptoms, but clinical significance unclear
  • tricyclic antidepressants may be more effective than placebo, effects consistent for desipramine but not for imipramine
  • atomoxetine (Strattera) reduced ADHD symptoms compared to placebo based on limited selected evidence
  • psychological/behavioral treatment - insufficient evidence
  • iron supplementation  may improve ADHD symptoms and severity in children with ADHD and low serum ferritin levels (level 2 [mid-level] evidence) (* further peer review in progress)
  • multimodal treatment generally recommended though not adequately studied
    • behavior modification - increase structure of environment, positive reinforcement
    • individual psychotherapy - improve self-esteem
    • parent counseling, parent training in behavior management
    • patient and family education about ADHD
    • social skills training
    • involvement of school teachers and counselors in assessment and management
    • stimulant medication - consider "n of 1" medication trial to determine effectiveness before chronic treatment
    • medication management either alone or combined with behavior treatment moderately superior to behavior treatment or "usual care" in 1 randomized trial

Diet :

  • elimination of certain substances (e.g. food dyes and preservatives) not proven to be effective
    • Feingold diet (elimination of certain foods and synthetic chemicals) has received widespread support despite lack of controlled clinical trials
    • studies of food dyes in children with ADHD have had inconsistent results 
    • oligoantigenic diet associated with limited behavioral improvement in crossover trial; 49 children with hyperactive/disruptive behavior disorder randomized to oligoantigenic diet vs. control diet in crossover fashion while in inpatient unit, 12 children (24%) showed significant behavioral improvement in 2 behavior ratings during diet relative to control diet conditions, methylphenidate used in 36 children yielded more responders (44%) than diet (Eur Child Adolesc Psychiatry 1997 Jun;6(2):88)
    • Reference - Altern Ther Health Med 2002 Jan-Feb;8(1):68, commentary can be found in Altern Ther Health Med 2002 May-Jun:8(3):18
  • food additives  might promote hyperactivity in children, but evidence limited and inconsistent
  • sugar challenges have not shown evidence of behavior problems in 12 double-blind placebo-controlled trials (Crit Rev Food Sci Nutr 1996 Jan;36(1-2):31) (* further peer review in progress)
  • essential fatty acid supplementation for 4 weeks had little or no benefit in randomized placebo-controlled crossover trial of 31 children with marked inattention and overactivity (J Abnorm Child Psychol 1987 Mar;15(1):75 in Altern Ther Health Med 2002 Jan-Feb;8(1):68)

Counseling :

  • parent training in child management techniques reduces ADHD symptoms and improves mothers' sense of well-being; 78 children 3 years old with "preschool equivalent of ADHD" were randomized to parent training vs. parent support (non-directive counseling) vs. wait list control for 8 weeks with 1-hour weekly home visits from therapist; parent training reduced ADHD symptoms and improved maternal well-being significantly compared to both other groups; recovery based on Parental Account of Childhood Symptoms ADHD/Hyperkinesis scale reported in 53% parent training group (NNT 4) vs. 39% parent support group vs. 25% wait list control group; effects maintained at 15-week follow-up (J Am Acad Child Adolesc Psychiatry 2001 Apr;40(4):402 in Evidence-Based Nursing 2001 Oct;4(4):109)
  • behavioral and social skills program improves behavioral management at home; 100 children 5-12 years old recently diagnosed with ADHD and treated with stimulants were randomized to intervention vs. control; intervention consisted of eight 50-minute group sessions over 8 weeks; evaluations at 3 and 6 months, intervention improved ADHD functioning in home setting, intervention group parents used behavior modification strategies more consistently, no differences in school setting (J Dev Behav Pediatr 2003 Feb;24(1):51 in Pediatric Notes 2003 Mar 27;27(13):49)
  • social skills training (group treatment) associated with improved activities of daily living in randomized trial of 27 children aged 5-8 years with ADHD (Dev Med Child Neurol 2005 Aug;47(8):539 in Pediatric Notes 2005 Oct 6;29(40):159)

Medications :

(* further peer review in progress)

Stimulants :

  • stimulants include methylphenidate, dexmethylphenidate, amphetamines, modafinil
    • methylphenidate

      • stimulant with pharmacologic actions similar to amphetamines
      • amphetamines have high potential for abuse and diversion, class II controlled substance
      • FDA approved for
        • attention-deficit hyperactivity disorder (ADHD) in children > 6 years old, adolescents and adults
        • narcolepsy
      • available in multiple formulations
        • tablets (5 mg, 10 mg, 20 mg) available as Methylin, Ritalin, generic
        • chewable tablets (Methylin) available in 2.5 mg, 5 mg and 10 mg
        • extended-release capsules available as Metadate CD (10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg) and Ritalin LA (10 mg, 20 mg, 30 mg, 40 mg)
        • extended-release tablets available as Metadate ER (10 mg, 20 mg), Methylin ER (10 mg, 20 mg), Ritalin-SR (20 mg) and generic (20 mg)
        • extended-release tablets with immediate-release component (Concerta) available in 18 mg, 27 mg, 36 mg and 54 mg
        • solution (Methylin) available in 5 mg/5 mL and 10 mg/5 mL
        • transdermal system (Daytrana) available in 10 mg/9 hours, 15 mg/9 hours, 20 mg/9 hours and 30 mg/9 hours
      • typical dose range 10-60 mg/day
      • efficacy
        • methylphenidate reduces core symptoms of ADHD in children ages 5-18 years in the short term (level 1 [likely reliable] evidence)
        • short-acting methylphenidate has significant clinical effect for at least 4 weeks
        • extended-release methylphenidate and immediate-release methylphenidate appear to have similar efficacy
        • Metadate CD and Concerta have similar overall efficacy but differ at different time points throughout the day, Metadate CD more effective in morning, Concerta more effective in early evening
        • methylphenidate appears to have little or no effect in preschool children with ADHD (level 2 [mid-level] evidence)
        • extended-release methylphenidate once daily may improve adolescent ADHD (level 2 [mid-level] evidence)
        • controlled-release methylphenidate may reduce inattentive driving errors in adolescents (level 2 [mid-level] evidence)
        • methylphenidate appears effective in adults with ADHD (level 2 [mid-level] evidence)
        • methylphenidate appears NO more effective than lithium or sustained-release bupropion in adults with ADHD (level 2 [mid-level] evidence)
        • methylphenidate may improve driving performance in adult males with ADHD (level 2 [mid-level] evidence)
      • cautions
        • contraindicated if marked agitation, glaucoma, motor tics (controversial), MAO inhibitors within 14 days
        • tolerance and psychological dependence may occur with chronic abuse
        • psychotic episodes can occur, especially with parenteral abuse
        • sudden death and cardiovascular disease has been reported
        • possible lowering of seizure threshold
      • American Heart Association suggests screening ECG before starting stimulant medications in children (grade C recommendation [lacking direct evidence])
      • Pregnancy Category C
      • common adverse effects include insomnia, headache, nervousness, abdominal pain, nausea, vomiting, anorexia, weight loss, affect lability, tic

    • dexmethylphenidate

    • amphetamine and dextroamphetamine

    • lisdexamfetamine dimesylate (Vyvanse)
      • manufacturer claims lower potential for abuse as active ingredient (d-amphetamine) is only released when swallowed
      • dosing information for lisdexamfetamine dimesylate (Vyvanse)
        • available in 20, 30, 40, 50, 60 and 70 mg capsules
        • dose 30-70 mg once daily
        • may increase at intervals of 1 week by 20 mg per day
        • maximum dose 70 mg per day
        • may dissolve contents of capsule in water; take immediately
        • do not subdivide capsule contents
        • Reference - Monthly Prescribing Reference 2007 Jul:A-17, Monthly Prescribing Reference 2008 Feb:A-18
      • do not combine or use within 2 weeks of monoamine oxidase inhibitor due to increased risk of hypertensive crisis (Prescriber's Letter 2007 May;14(5):28)
      • no evidence that lisdexamfetamine dimesylate offers any therapeutic advantage over other amphetamines for treatment of children with ADHD (The Medical Letter 2007 Jul 16;49(1265):58)
    • modafinil may be effective for children with ADHD (level 2 [mid-level] evidence)

    • pemoline (Cylert and generics) discontinued in United States, FDA concluded that risk of liver toxicity outweighs benefits (FDA MedWatch 2005 Oct 24)
  • warnings and cautions
    • guidelines regarding screening ECG before starting stimulant medications in children are inconsistent (* further peer review in progress)
      • American Heart Association suggests screening ECG before starting stimulant medications in children (grade C recommendation [lacking direct evidence])
        • rationale
          • rare association of sudden cardiac death with stimulant drugs presumed to be in predisposed patients
          • stimulant drug monographs generally state drug should not be used in children with serious cardiac problems
        • screening considerations to identify heart disease
          • patient and family history, including fainting or dizziness, seizures, rheumatic fever, chest pain or shortness of breath with exercise, unexplained change in exercise tolerance, palpitations, increased heart rate, extra or skipped heart beats, high blood pressure, heart murmur (other than innocent or functional murmur) or history of other heart problems, intercurrent viral illness with chest pains or palpitations, current medications and health supplements
          • physical exam, including evaluation for abnormal heart murmur, hypertension, arrhythmia, tachycardia and physical findings suggestive of Marfan's syndrome
          • baseline electrocardiogram (repeated after age 12 years if baseline ECG conducted prior to age 12 years)
        • reasonable to check history, physical examination, and ECG for children already taking stimulants
        • Reference - Circulation 2008 May 6;117(18):2407 PDF
      • American Academy of Pediatrics (AAP) does not recommend routine ECG prior to treatment of ADHD in children (grade C recommendation [lacking direct evidence])
        • AAP finds no compelling evidence of increased risk of sudden death in children treated for ADHD
        • physicians encouraged to carefully assess all children for cardiac abnormalities by reviewing history and physical assessments
        • Reference - AAP policy statement on cardiovascular monitoring and stimulant drugs for ADHD (Pediatrics 2008 Aug;122(2):451)
    • risk of abuse may be a concern in some patients with ADHD but no evidence for causing substance abuse
      • stimulant therapy for 12-18 weeks in childhood does not increase risk of subsequent substance abuse; 109 children ages 7-12 years with developmental reading disorder and no other psychiatric morbidity were randomized to methylphenidate vs. placebo for 12 or 18 weeks in 2 trials, 94% were followed up at 16 years (mean age 26 years); no significant differences in substance use disorders (abuse or dependence) for 7 drugs evaluated, 46% vs. 41% ever used stimulants in adolescence or adulthood (compared to 60% for 129 non-trial controls) (J Child Adolesc Psychopharmacol 2003 Fall;13(3):273 in Pediatric Notes 2003 Dec 18;27(51):201)
      • stimulant therapy in childhood is associated with reduced risk for subsequent drug and alcohol use disorders, based on meta-analysis of 6 cohort studies (Pediatrics 2003 Jan;111(1):179), commentary can be found in Evidence-Based Medicine 2003 Nov-Dec;8(6):188
      • stimulant therapy NOT associated with substance abuse in 13-year follow-up of 147 hyperactive children, no compelling evidence for such an association in 11 previous studies (Pediatrics 2003 Jan;111(1):97), summary can be found in Am Fam Physician 2003 Apr 15;67(8):1797, commentary can be found in Pediatrics 2003 Dec;112(6):1459
    • stimulant therapy might be associated with growth delay (level 2 [mid-level] evidence)
      • systematic review of 22 studies of growth in height in children with ADHD on stimulant medications
      • 11 studies suggested height attenuation, estimated height deficit about 1 cm/year for first 1-3 years of treatment
      • 11 studies not suggesting height attenuation all had methodologic limitations
      • Reference - Arch Dis Child 2005 Aug;90(8):801
      • stimulant therapy NOT associated with growth retardation in girls; previous studies showing lack of meaningful effects of stimulants on ADHD patients were mostly limited to boys; comparison of 124 girls with ADHD and 116 control girls found no association with growth parameters (annual meeting of Pediatric Academic Societies 2003 May 3-6 in Pediatric Notes 2003 Jun 12;27(24):96)
    • stimulant therapy does NOT affect tics
      • studies have failed to confirm the hypothesis that stimulant drug therapy exacerbates tic severity (Pediatrics 1999 Apr;103(4 Pt 1):730 in Pediatric Notes 1999 May 13;23(19):75)
      • average doses of methylphenidate do not significantly cause or worsen tics; 91 children with ADHD and no or mild to moderate tics randomized to methylphenidate (average 0.5 mg/kg twice daily) vs. placebo for 1 year, 19.6% vs. 16.7% those without preexisting tics developed clinically significant tics, 33% vs. 33% had worsening of preexisting tics (J Am Acad Child Adolesc Psychiatry 1999 Aug;38(8):944 in Pediatric Notes 1999 Aug 12;23(32):127)
      • withdrawal of stimulants in placebo-controlled double-blind fashion did not change frequency or severity of tics in series of 19 children with ADHD and vocal or motor tics who have been on stimulants for long time (Pediatrics 1999 Apr;103(4 Pt 1):730 in Pediatric Notes 1999 May 13;23(19):75)
  • medication management either alone or combined with behavior treatment moderately superior to behavior treatment or "usual care" (which may include medications) for ADHD symptoms
  • side effects attributed to stimulants may actually be features of ADHD or overreporting of symptoms in trials
    • 125 children aged 5-15 years randomized to methylphenidate 0.3 mg/kg vs. dexamphetamine 0.15 mg/kg orally twice daily for 2 weeks each in crossover fashion
    • certain behaviors (nightmares, stomachaches and anxiousness) were reportedly more frequent before the trial of medication and decreased with methylphenidate
    • only poor appetite increased with methylphenidate
    • dexamphetamine associated with increased insomnia and poor appetite
    • Reference - Pediatrics 1997 Oct;100(4):662 in Am Fam Physician 1998 Feb 1;57(3):544
  • weekend drug holidays may reduce side effects without reducing efficacy (level 2 [mid-level] evidence); 40 boys with ADHD treated with methylphenidate and randomized to methylphenidate vs. placebo on weekends for 3 weeks; methylphenidate dose increased weekly from 0.3 mg/kg/day to 0.5 mg/kg/day to 0.7 mg/kg/day unless side effects; no significant differences in 10-li Conners' Abbreviated Rating Scale scores on parent weekend ratings or teacher ratings, weekend drug holiday associated with less severity of insomnia (p = 0.05) and less interference with appetite (p = 0.08) (J Child Adolesc Psychopharmacol 2004 Summer;14(2):195 in Pediatric Notes 2004 Sep 30;28(40):159)
  • comparisons between stimulant therapies
    • few, if any, differences among methylphenidate, dextroamphetamine, and pemoline in AHRQ evidence-based review of 23 trials (Evid Rep Technol Assess (Summ) 1999 Nov;(11):i-viii, 1-341)
    • comparisons of methylphenidate and dextroamphetamine inconsistent
      • based on systematic review (Am Fam Physician 2003 May 1;67(9):1969 full-text)
      • methylphenidate 0.3 mg/kg twice daily and dexamphetamine 0.15 mg/kg twice daily had similar efficacy in 2-week crossover trial in 125 children with ADHD (Pediatrics 1997 Dec;100(6):e6 full-text)
      • dextroamphetamine (Adderall) 7.5 mg twice daily as effective as methylphenidate (Ritalin) 17.5 mg twice daily and lasted longer in randomized daily crossover trial with placebo control over 24 days in 25 children in summer day program, lower doses of Ritalin less effective, higher doses of Adderall no more effective and less desired (Pediatrics 1999 Apr;103(4):e43 full-text)
      • dextroamphetamine (Adderall) once daily as effective as methylphenidate (Ritalin) twice daily in randomized daily crossover trial with placebo control in 21 children aged 6-12 years in intensive summer day program, methylphenidate once daily less effective overall but still effective in some patients (Pediatrics 1999 Dec;104(6):1300); study funded by Adderall manufacturer (Pediatric Notes 2000 Jan 27;24(4):16), summary can be found in Am Fam Physician 2000 May 1;61(9):2839
  • consider "n of 1" medication trial
    • placebo-controlled, double-blind (teacher and parents), low-dose medication for 1 week, placebo for 1 week, high-dose medication for 1 week, behavior questionnaire each week
    • determines effectiveness before chronic treatment
    • double-blind "n of 1" trials found useful in case series; 50 families of children with ADD given 3 identical bottles of Ritalin 0.3 mg/kg, Ritalin 0.6 mg/kg or placebo with family, teacher and physician blinded to order of medication; Conners questionnaires completed at baseline and end of each week, 43 families were contacted for evaluation, none found trial difficult, 6 trials incomplete; overall 72% good response to Ritalin, 47% continued Ritalin > 1 year; of 9 families choosing not to use long-term Ritalin, all indicated trial helped their decision-making (Pediatric Notes 1998 Jul 2;22(27):107, published in Arch Pediatr Adolesc Med 1999 Dec;153(12):1292 in Pediatric Notes 2000 Jan 6;24(1):2)
    • n-of-1 trials may change management in 44% cases
      • n-of-1 trial service described for within-patient randomized placebo-controlled trials of dexamphetamine or methylphenidate for children ages 5-16 years with ADHD on stable stimulant doses in Australia
      • 45 doctors requested 108 n-of-1 trials, 86 trials were completed
      • 29 of 69 children in drug vs. placebo comparisons responded better to stimulant, 13 of 24 nonrespondents stopped or changed stimulants
      • for patients with data available, 40 of 63 had posttrial management consistent with trial results, 28 of 64 (44%) had change in management
      • Reference - Pediatrics 2006 Jun;117(6):2040
    • series of n-of-1 trials in 21 children with ADHD described in Br J Gen Pract 2005 Mar;55(512):175 (Fam Med 2006 Jan;38(1):63 PDF)
  • arguments for and against use of stimulants for ADHD can be found in BMJ 2004 Oct 16;329(7471):907 and 908

Atomoxetine :

30-day costs of drugs for ADHD :

  • costs noted are for typical pediatric dose for 30 days, all medications listed except atomoxetine are classified by DEA as Schedule II controlled substances
  • amphetamines
    • do NOT take with antacids or other drugs that decrease gastric acidity
    • amphetamine mixture
      • short-acting (duration of action 4-6 hours)
        • 10 mg twice daily - generic $66.60, Adderall $138.00
        • initial dose 5 mg twice daily
        • adult dose initially 5 mg twice daily, typical adult dose 15 mg twice daily
      • Adderall XR lasts 8-10 hours, given as 30 mg once daily in the morning $113.10
        • initial dose 5 mg once daily in the morning
        • adult dose initially 5 mg once daily, typical adult dose 60 mg once daily in the morning
    • dextroamphetamine
      • short-acting (duration of action 4-6 hours)
        • 10 mg twice daily - generic $32.40, Dextrostat $27.60, Dexedrine $67.20
        • initial dose 5 mg twice daily
        • adult dose initially 5 mg twice daily, typical adult dose 15 mg twice daily
      • long-acting (duration of action lasts 6-8 hours)
        • 15 mg once daily in the morning - generic $33.30, Dexedrine Spansules $62.70
        • initial dose 5 mg once daily
        • adult dose initially 5 mg once daily, typical adult dose 30 mg once daily
  • atomoxetine (Strattera) 1.2 mg/kg/day once daily or in 2 divided doses, $129.00 for 30 capsules (60 mg)
    • duration of action 24 hours
    • initial dose 0.5 mg/kg/day
    • adult dose initially 40 mg once daily, typical adult dose 80 mg once daily or in 2 divided doses
  • dexmethylphenidate
    • Focalin 5 mg each morning $25.20
      • duration of action 5-6 hours (may need twice daily dosing)
      • initial dose 2.5 mg each morning
      • adult dose initially 5 mg each morning, typical adult dose 20 mg each morning
    • Focalin XR 10 mg each morning $102.00
      • duration of action 12 hours
      • take with antacids or other drugs that decrease gastric acidity
      • initial dose 5 mg each morning
      • adult dose initially 5 mg each morning, typical adult dose 20 mg each morning
  • methylphenidate
    • immediate release short-acting (duration of action 3-5 hours)
      • 10 mg 3 times daily - generic $38.70, Ritalin $79.20, Methylin $28.80, Methylin Chewable Tablets $81.00, Methylin Oral Solution $94.50
      • initial dose 5 mg 3 times daily
      • adult dose initially 10 mg twice daily, typical adult dose 20 mg 3 times daily
    • intermediate-acting (duration 3-8 hours)
      • 40 mg once daily in the morning - generic $54.60, Ritalin SR $112.80
        • initial dose 20 mg once daily
        • adult dose initially 20 mg once daily, typical adult dose 80 mg once daily
      • 30 mg once daily in the morning - Metadate ER $54.90, Methylin ER $49.80
        • initial dose 10 mg twice daily
        • adult dose initially 10 mg once daily, typical adult dose 80 mg once daily
    • long-acting (duration 8-12 hours)
      • Concerta 36 mg once daily in the morning $111.90
        • duration of action 10-12 hours
        • initial dose 18 mg once daily
        • adult dose initially 18 mg once daily, typical adult dose 72 mg once daily
      • Metadate CD 30 mg once daily $76.80
        • duration of action 8-12 hours
        • initial dose 10 mg once daily
        • adult dose initially 20 mg once daily, typical adult dose 80 mg once daily
      • Ritalin LA 30 mg once daily $89.70
        • duration of action 8-12 hours
        • initial dose 10 mg once daily
        • adult dose initially 10 mg once daily, typical adult dose 80 mg once daily
      • Daytrana transdermal patch 30 mg patch on 9 hours/off 15 hours $141.60
        • duration of action 10-12 hours
        • initial dose 10 mg patch on 9 hours/off 15 hours
        • adult dose initially 10 mg patch on 9 hours/off 15 hours, typical adult dose 60 mg patch on 9 hours/off 15 hours
  • Reference - Treatment Guidelines from The Medical Letter 2006 Nov;4(51):77
  • lisdexamfetamine dimesylate (Vyvanse)
    • long-acting (duration of action 10 hours)
    • 30 mg once daily in the morning $128.00
    • typical pediatric dose 30-50 mg once daily in the morning
    • no recommended adult dose, only FDA-approved for children aged 6-12 years
    • Reference - The Medical Letter 2007 Jul 16;49(1265):58
  • pemoline (Cylert and generics) discontinued in US as FDA concluded that risk of liver toxicity outweighs benefits (FDA MedWatch 2005 Oct 24)

Antidepressants :

  • tricyclic antidepressants may be more effective than placebo based on 9 trials, effects consistent for desipramine but not for imipramine (Evid Rep Technol Assess (Summ) 1999 Nov;(11):i-viii, 1-341)
  • laboratory testing needed for tricyclic antidepressants in children
  • desipramine appears effective for ADHD and chronic tic disorder
    • based on randomized trial
    • 41 children and adolescents with chronic tic disorders and comorbid ADHD were randomized to desipramine (titrated weekly up to 3.5 mg/kg/day) vs. placebo for 6 weeks
    • desipramine significantly reduced core symptoms of ADHD (42% decrease from baseline relative to placebo) with equal response in inattentive symptoms and hyperactive/impulsive symptoms
    • desipramine significantly reduced tic symptoms (30% decrease from baseline relative to placebo) with equal response in motor and phonic tic symptoms
    • Reference - Arch Gen Psychiatry 2002 Jul;59(7):649
  • comparisons of methylphenidate and antidepressants
    • comparisons of imipramine and methylphenidate inconclusive (Am Fam Physician 2003 May 1;67(9):1969 full-text)
    • bupropion might be effective for ADHD (level 2 [mid-level] evidence)
      • based on small randomized crossover trial
      • 15 children aged 7-17 years with ADHD randomized to bupropion vs. methylphenidate for 6 weeks each with 2-week washout inbetween
      • bupropion titrated to effective dose 1.4-5.7 mg/kg/day (mean 3.3 mg/kg/day)
      • methylphenidate titrated to maximum effective dose 0.4-1.3 mg/kg/day (mean 0.7 mg/kg/day)
      • both groups had similar improvements on multiple rating scales
      • some nonsignificant trends favoring methylphenidate
      • Reference - J Am Acad Child Adolesc Psychiatry 1995 May;34(5):649 in QuickScan Reviews in Fam Pract 1995 Dec:4
  • St. John's wort appears similar to placebo for treatment of ADHD in children (level 2 [mid-level] evidence)
    • based on small randomized trial
    • 54 children aged 6-17 years with ADHD had 1 week placebo run-in then randomized to St. John's wort (Hypericum perforatum) 300 mg (standardized to 0.3% hypericin) vs. placebo 3 times daily for 8 weeks
    • other ADHD medications prohibited
    • no significant differences in
      • patients meeting criteria for improvement on Clinical Global Impression Improvement Scale
      • inattentiveness score
      • hyperactivity score
      • adverse effects
    • Reference - JAMA 2008 Jun 11;299(22):2633, editorial can be found in JAMA 2008 Jun 11;299(22):2685

Alpha-2-aderenergic agonists (Clonidine, Guanfacine) :

  • alpha 2 -adrenergic agonists (not FDA approved for ADHD)
    • insufficient evidence to conclude effectiveness but suggestive improvements seen in impulsivity and hyperactivity, comorbid tics or insomnia with stimulants
    • effect seen after 4-6 weeks of treatment
    • review personal and cardiovascular history
    • taper off gradually over 1-2 weeks to avoid rebound increase in blood pressure
    • clonidine (Catapres, Clorpres)
      • available in 0.1, 0.2, 0.3 mg tablets
      • initial dose 0.1 mg at bedtime (0.05 mg if < 45 kg)
      • maximum dose 0.4 mg (0.2 mg if 27-40.5 kg, 0.3 mg if 40.5-45 kg)
    • guanfacine
      • available as generic, Tenex (1, 2 mg tablets)
      • initial dose 1 mg at bedtime (0.5 mg if < 45 kg)
      • maximum dose 4 mg (2 mg if 27-40.5 kg, 3 mg if 40.5-45 kg)
    • Reference - American Academy of Child and Adolescent Psychiatry practice parameter for assessment and treatment of children and adolescents with ADHD (J Am Acad Child Adolesc Psychiatry 2007 Jul;46(7):894 PDF or at National Guideline Clearinghouse 2007 Dec 10:11375)
  • clonidine
    • clonidine more effective than placebo in reducing ADHD symptoms, but clinical importance unclear, based on systematic review of placebo-controlled trials lasting 4-12 weeks (Am Fam Physician 2003 May 1;67(9):1969 full-text)
    • clonidine appears to have moderate effect on ADHD symptoms
    • clonidine may reduce conduct problems in children with ADHD and oppositional defiant disorder or conduct disorder (level 2 [mid-level] evidence); 67 children aged 6-14 years with ADHD and oppositional defiant disorder or conduct disorder who had received psychostimulant for at least 3 months were randomized to clonidine 0.5 mg twice daily (increased to 1 mg twice daily after 1 week, but morning dose decreased to 0.5 mg if excessive sedation) vs. placebo for 6 weeks, stimulants continued; 57% vs. 21% improved by > 37% on conduct scale (NNT 3) (J Am Acad Child Adolesc Psychiatry 2003 Aug;42(8):886 in QuickScan Reviews in Fam Pract 2004 Jan 2;29(5):17)
    • clonidine and methylphenidate both effective individually and in combination for reducing ADHD symptoms and tic severity in children with ADHD and chronic primary tic disorder, based on randomized 4-way placebo-controlled trial of 136 such children aged 7-14 years (Neurology 2002 Feb 26;58(4):527 in ACP J Club 2002 Sep-Oct;137(2):70)
    • clonidine 3-5 mcg/kg/day in divided doses
      • no published comparison studies with methylphenidate
      • published trials of clonidine limited to small studies
      • 7 of 10 children showed benefit in crossover trial (J Am Acad Child Psychiatry 1985 Sep;24(5):617)
      • clonidine has improved ADHD symptoms in small trials of patients with autism or Tourette's syndrome
      • adverse effects - irritability and sedation common; hypotension, bradycardia, rebound hyperactivity and tics; at least 5 unexplained deaths
      • Reference - The Medical Letter 1996 Dec 6;38(989):109
  • guanfacine
    • guanfacine extended release may improve ADHD symptoms and severity in children but may increase risk of adverse events (level 2 [mid-level] evidence)
      • based on randomized trial with high drop out rate
      • 345 children aged 6-17 years with ADHD randomized to guanfacine extended release (2 mg/day vs. 3 mg/day vs. 4 mg/day) vs. placebo for 8 weeks
      • 62% completed study
      • comparing combined guanfacine groups vs. placebo
        • rate of drop out due to adverse events 16.2% vs. 1.2%
        • rate of drop out due to lack of efficacy 8.1% vs. 17.4%
      • significant improvement in ADHD Rating Scale-IV scores for GXR doses > 0.05 mg/kg compared to placebo
      • adverse events included somnolence, fatigue, upper abdominal pain, sedation and headache (average length of exposure 42 days)
        • mild and moderate adverse events in 50.6% guanfacine vs. 10.5% placebo
        • severe adverse events in 6.2% guanfacine vs. 0 placebo
      • Reference - Pediatrics 2008 Jan;121(1):e73
    • guanfacine (Tenex) appears safe and effective for children with tic disorders and ADHD; 34 medication-free children from a specialty tic disorders clinic with both ADHD and a tic disorder were randomized to guanfacine vs. placebo for 8 weeks, 37% vs. 8% mean improvement in total score on teacher-rated ADHD Rating Scale, 53% vs. 0 were blindly rated on Clinical Global Improvement scale as either much improved or very much improved (NNT 2), 27% vs. 21% improvement in mean score on parent-rated hyperactivity index (not significant), decreased vs. increased errors on Continuous Performance Test, tic severity decreased by 31% vs. 0%, guanfacine associated with insignificant decreases in blood pressure and pulse and 1 withdrawal due to sedation (Am J Psychiatry 2001 Jul;158(7):1067)

Mineral supplementation :

  • zinc sulfate may improve efficacy of methylphenidate over 6-12 weeks
    • 400 children with ADHD randomized to zinc sulfate 150 mg/day vs. placebo for 12 weeks; zinc sulfate reduced hyperactive and impulsive symptoms but no difference in attention deficiency symptoms, 53% had metallic taste with zinc sulfate, excess zinc can cause sideroblastic anemia and copper deficiency (Prog Neuropsychopharmacol Biol Psychiatry 2004 Jan;28(1):181 in Prescriber's Letter 2004 Aug;11(8):46)
    • 44 children with ADHD (baseline Parent ADHD scale score 31 and Teacher ADHD scale score 32) treated with methylphenidate 1 mg/kg/day and randomized to zinc sulfate 55 mg/day (elemental zinc 15 mg/day) vs. placebo (sucrose 55 mg/day) for 6 weeks, 40 (91%) completed the trial; Parent ADHD scale scores decreased to 15 vs. 25, Teacher ADHD scale scores decreased to 16 vs. 24; adverse effects included metallic taste (59% vs. 0, NNH 1.7) and nausea (41% vs. 14%, NNH 3.7) (BMC Psychiatry 2004 Apr 8;4:9 full-text)
  • iron supplementation may improve ADHD symptoms and severity in children with ADHD and low serum ferritin levels (level 2 [mid-level] evidence)
    • based on small randomized trial
    • 23 non-anemic children aged 5-8 years with ADHD and serum ferritin levels < 30 ng/mL were randomized to oral iron (ferrous sulfate 80 mg/day) vs. placebo for 12 weeks
    • significant improvements observed in
      • ADHD symptoms with iron (p < 0.008) but not with placebo (p = 0.308)
      • severity score with iron (p < 0.01) and no change with placebo
    • trend for improvement with iron vs. placebo on parent (p = 0.055) and teacher (p = 0.076) rating scales
    • Reference - Pediatr Neurol 2008 Jan;38(1):20

Other medications :

  • carbamazepine may be effective for treating ADHD, particularly as second-line drug in stimulant-resistant patients (25%); systematic review identified 10 studies using carbamazepine in children and adolescents with behavioral problems, 7 uncontrolled studies with 189 patients, 3 randomized double-blind placebo-controlled with 105 patients; meta-analysis of randomized trials found 71% response rate with carbamazepine and 26.3% placebo response rate with responses defined as substantial improvement in target symptoms; target symptoms were hyperkinesia, behavior disturbances and behavior problems in the three trials; major criticisms of meta-analysis are that diagnostic criteria varied between reports, so unclear whether all had ADHD, and outcomes measured varied between reports (J Am Acad Child Adolesc Psychiatry 1996 Mar;35(3):352 in QuickScan Reviews in Fam Pract 1996 Oct;21(7):18)
  • docosahexaenoic acid (DHA) supplementation for 4 months did not decrease symptoms of ADHD; 63 children aged 6-12 years with ADHD receiving effective maintenance therapy with stimulants were randomized to DHA 345 mg/day vs. placebo for 4 months, no significant differences in any objective or subjective measures of ADHD symptoms or parental behavior ratings (J Pediatr 2001 Aug;139(2):189)
  • essential fatty acid (EFA) supplementation appears to have little effect in hyperactive children (level 2 [mid-level] evidence)
    • based on small randomized crossover trial
    • 31 children with marked inattention and hyperactivity were given EFA supplementation (evening primrose oil [Efamol]) vs. placebo for 4 weeks each in crossover trial
    • only 2 of 42 outcomes had statistically significant treatment effects
    • Reference - J Abnorm Child Psychol 1987 Mar;15(1):75

Consultation and referral :

  • consider referral to a child psychiatrist when the diagnosis is in doubt or for management of difficult cases
  • communicate with and encourage communication among parents, teachers and counselors
  • behavior modification techniques in management of disruptive classroom behavior can be found in Clin Pediatrics (Phila) 1976 Jun;15(6):510

Other management :

  • neurofeedback has been advocated but evidence very limited; 18 children with ADHD randomized to EEG biofeedback (40 sessions over 6 months) vs. waiting list, average IQ scores increased 9 points more in experimental group than control group (p = 0.023), treatment reduced inattentive behaviors (p = 0.04) (Biofeedback Self Regul 1996 Mar;21(1):35 in Alternative Medicine Alert 2001 Sep;4(9):97)
  • insufficient evidence regarding family therapy; systematic review of 2 randomized trials of behavioral family therapy for children with ADD or ADHD, 1 trial found no difference compared to usual treatment, 1 trial found slight benefit favoring behavioral family therapy over medication placebo, no trials found for cognitive behavioral family therapy or functional family therapy; systematic review last updated 2005 Feb 22 (Cochrane Library 2005 Issue 2:CD005042)
  • insufficient evidence to evaluate homeopathy treatments in children with ADHD
    • based on Cochrane review
    • systematic review of 4 randomized or quasi-randomized trials evaluating individualized, clinical or formula homeopathy in 168 patients with ADHD or hyperkinetic disorder
    • all trials evaluated children
    • no significant treatment effects for global symptoms, core symptoms of inattention, hyperactivity or impulsivity, or related outcomes (such as anxiety)
    • specific outcomes evaluated in only 1 trial or meta-analysis of 2 trials
    • Reference - systematic review last updated 2007 Aug 20 (Cochrane Library 2007 Issue 4:CD005648)
  • homeopathy had mixed results in children with ADHD in systematic review of 3 randomized trials (Mayo Clin Proc 2007 Jan;82(1):69)

Follow-up :

  • children may be able to be off medication when not in school (e.g. summer vacation)

Prevention and Screening

Screening :

    (* further peer review in progress)

  • Conner's Rating Scales wides used for screening for ADHD in children
  • no test demonstrated to be useful for screening for ADHD in children with intellectual disabilities (J Intellect Disabil Res 2008 Jan 2 early online)

References (including Reviews and Guidelines)

General references used :

Reviews :

Guidelines :

Patient Information

Patient information :