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attention-deficit hyperactivity disorder (ADHD)

ADHD is a commonly used acronym for Attention-deficit hyperactivity disorder. Classification: - childhood & adult onset forms may represent 2 distinct clinical entities [47] Etiology: - television > 3 1/2 hours/day may increase risk [6] - digital media activities several times daily (chatting, gaming) increase risk for developing ADHD [62] - food additives may increase risk [12] - consumption of sweetened beverages by children & adolescents may increase risk of hyperactivity/inattention behaviors [39] - in utero exposure to acetaminophen may increase risk [35,54] - sleep disorder ? [37] - attention-deficit hyperactivity disorder symptoms may mask underlying autism in young children [42] - maternal mental health disorder [51] - traumatic brain injury (TBI) among children 3-7 years of age at the time of TBI - ADHD may manifest as late as 7 years after TBI [60] - more severe cases of ADHD occur within 18 months [60] - hypertension during pregnancy [61] - maternal autoimmune disease including type 1 diabetes, psoriasis, & rheumatic heart disease increase risk (RR=1.27 boys, RR=1.36 girls) [70] - younger children in a school grade cohort at higher risk [65] - not risk factors - maternal antidepressant use during pregnancy [51]* - 1st trimester antidepressant use not associated with increased risk of ADHD in offspring [49] * maternal mental health may be linked to ADHD in offspring [51] Epidemiology: 1) 8-16% of children [4]; 3-5% [7]; 9% [13] - 6% of girls [48], 3-fold more common in boys [70] 2) 4 million cases in US [20] 3) most children have comordid conditions [20] - most late onset associated with cormorbid condition including mood disorders & substance abuse [56] 4) youngest children in a school grade may be more likely to be diagnosed with ADHD & to receive treatment [45] 5) 60% of cases continue into adulthood [8] - late onset = age 10-25 years [56] 6) prevalence of ADHD in adults has increased 0.43%-0.96% from 2007-2016 [69] Genetics: - breakpoint in gene for Na+/H+ exchanger 9 inversion inv(3)(p14:q21),inversion disrupts DOCK3 & SLC9A9 - intron variant in GIT1 associated with ADHD [21] - associated with variations in CACNA1C & CACNB2 [29] - CNTN4 gene mutation (contactin-4), present in 19% of adolescents with ADHD [57] Clinical manifestations: 1) snoring in 22% vs 12% of controls [3] 2) daytime sleepiness 3) inability to organize personal life & school work 4) inability to complete projects, chores & homework 5) trouble paying attention to & responding to details (inattention) 6) hyperactivity, fidgeting 7) impulsivity, excessive vocalization 8) onset before 7 years of age [18] - must be present since 12 years of age [18] - must interfere with function in at least 2 different settings (home, work) [18] Laboratory: - serum ferritin levels may be low (< 30 ng/mL) despite normal hemoglobin & serum iron [9] Special laboratory: - ECG if prescribing stimulant & there are concerns about congenital heart defects [14] Complications: - substance abuse (HR=6) [25] - long term combined use of stimulants & opiates common [65] - increased risk for premature death (RR=2.6) [38] - increased risk of accidential injury (RR=1.3) [41] - increased risk of automobile accidents may be reduced by pharmacologic therapy [50]; not reduced [52] - increased risk for psychiatric comorbidities [48] - oppositional defiant disorder (42% vs 5%) - conduct disorder (13% vs 1%) - anxiety disorder (38% vs 14%) - depression (10% vs 3%) [48] - adult ADHD ia associated with an increased risk for dementia (RR=2.8-3.6) [74] - vascular dementia most likely dementia type [76] - youngest classmates may be misdiagnosed with ADHD [55] - age differences of a few months are associated with noticeable motor & cognitive differences (until age 10) - increased risk to teenage pregnancy (RR=5) [68] - increased risk of keratoconus in males due to excessive eye rubbing [75] Management: 1) cognitive behavioral therapy a) 1st line treatment in children age 4-5 [22] b) parent behavioral training more effective than methylphenidate in preschool children at risk for ADHD [31] c) for use in conjunction with pharmacotherapy in older children [22] d) behavioral sleep intervention [37] e) just over 50% of affected children receive psychological services [46] 2) stimulant therapy a) avoid in patients with history of substance abuse; use atomoxetine [18] b) methylphenidate* - reduces risk of substance abuse (16% vs 42%) [5] - may improve symptoms of ADHD in children & adolescents [43] - may improve classroom behavior in children with ADHD [72] - zinc sulfate 55 mg (15 mg elemental Zn+2) allegedly improves effectiveness of methylphenidate [7] - more effective than atomoxetine in children [15] - drug of choice for children (<= 12 weeks of therapy) [63] c) amphetamine - drug of choice for adults (<= 12 weeks of therapy) [63] - Adderall XR* 20 mg PO QD [8] - dextroamphetamine* also useful, but not FDA approved [8] d) stimulants improve IQ scores [11] e) stimulant use delays growth in boys, but does not affect adult height [36] f) simulants reduce risk of accidental injury in ADHD children to risk similar to that of normal children [41] g) stimulants reduce emergency department visits in ADHD children [41] 3) safety issues of stimulants under investigation; [16] a) long-term effects of stimulants on brain development not known [40] b) concern for unexplained sudden death c) no increase in risk of sudden death [23] d) no increase in cardiovascular risk (see ADHD medication) e) potential risk of cardiac arrest & tachyarrhythmias [71] f) parents should not stop a child's stimulant medication g) avoid stimulants in patients with serious arrhythmias, symptomatic heart disease, or recent cardiovascular event h) management of stimulant side effects [30] 4) atomoxetine* (Strattera) a) preferred over stimulants in patients with a history of substance abuse [18] b) 40-100 mg QD works well in adults [8] c) 1/2 of patients who do not respond to methylphenidate will respond to atomoxetine [15] 5) viloxazine (Qelbree) may be more effective than atomoxetine [73] 6) other agents - bupropion or venlafaxine may be useful [8] - guanfacine used as 2nd line agent, but may be no better than placebo [44] 7) frequently used substances WITHOUT proven benefit a) Efalex Focus b) Pedi-Active ADD c) Kid's Companion Attention/Memory Formula d) essential fatty acids 1] gamma-linolenic acid 2] docosahexaenoic acid e) phosphatidylserine f) acetylcarnitine g) dimethylaminoethanol (DMAE, Deaner) h) Ginkgo biloba i) Ephedra 8) external trigeminal nerve stimulator [66] FDA-approved April 2019 9) screening: all children age 4-18 with academic or behavioral problems plus inattention, hyperactivity, or impulsivity [22] 10) prognosis: a) delay of treatment associated with decline in school performance [26] b) no cure; children seldom outgrow it c) gradual improvement with age in most patients [18] d) deficits persist at least 3 decades [27] - as adults, boys with ADHD - lower educational achievement - lower occupational levels - lower salaries - higher rates of substance abuse - higher rates of antisocial personality disorder e) treatment may reduce criminal conviction rates in male & female patients with ADHD [28] f) some find adaptive ways to deal with disorder 11) periodic drug holidays for adults may be useful for assessing need for continued medication [18] 12) organizations providing assistance [7,15] * agents under FDA investigation for adverse effects [10] Notes: - DSM-5 causes concern for overdiagnosis [32] - ADHD often overdiagnosed & overtreated, a trend fueled by pharmaceutical advertisements targeting physicians & parents [34] - ADHD medications diverted by parents [53] - adherence to ADHD medications low at start & end of fall semester, especially among first-year students [58] - sharing of ADHD medications offered as partial explanation

Interactions

disease interactions

General

inattention (poor concentration, attention disorder) learning disorder (learning disability)

Database Correlations

OMIM correlations

References

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  8. Prescriber's Letter 11(10): 2004 Attention-deficit Hyperactivity Disorder in Adults: An Update Detail-Document#: 201001 (subscription needed) http://www.prescribersletter.com
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