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Attention-Deficit/Hyperactivity Disorder D. Seltzer, M.D. 1/3/2012 ADHD - Epidemiology The MOST COMMON neurobehavioral disorder of childhood One of the most extensively studied behavioral disorder in school-age children One of most prevalent CHRONIC health conditions affecting school-age children Background: NOT a new disorder (1900) Stimulant therapy since the 1940’s ADHD - Epidemiology Prevalence range 1-16% Based on Criteria, Setting, SEC, Geographic area Most epidemiologic studies suggest 5-8% Dx in Boys is 2.5% >Girls 9.2% ♂; 2.9% ♀ ADHD – Epidemiology / Prognosis PERSISTS into adolescence and adulthood: 6085% of pts diagnosed in childhood. Hyperactivity diminishes (tho adolescents/adults may report subjective feelings of restlessness) Impulsivity and Inattention persist ADHD – Epidemiology / Prognosis Impulsivity and Inattention persist Adolescents: often immature peer relationships Adolescents (untreated): High Risk Behaviors ↑ auto accidents, initiate intercourse sooner, ↓ use bc, more sexual partners, ↑ STD’s, ↑ TA pregnancies, smoke at younger age poor teacher relationships, impaired school functioning, underachievement, esp reading. Adolescents with CD ↑ risk for substance abuse Risk for substance use d/o over lifespan 2x greater in pts w ADHD GIRLS: ↑anxiety, depression, ↓external locus of control. ADHD – Epidemiology / Prognosis Adults with ADHD Fewer yrs of education Lower rates of professional employment Lower SEC ↑ work difficulties More job changes More psychological maladjustment More problems w legal system: arrests, traffic tickets, MVA Co-morbidities highly influence prognosis ADHD CORE SYMPTOMS ADHD CORE SYMPTOMS Hyperactivity Impulsivity Inattention ADHD - Types Three Subtypes Predominantly hyperactive-impulsive type Predominantly inattentive type Combined type Predominantly Inattentive: Girls > Boys ADHD - Associations ASSOCIATIONS that contribute to Functional Impairments include School failure poor peer relationships Low self-esteem and self perception Lower academic achievement Accidental injuries Overall adaptive function Family dysfunction ADHD: Impaired Neurologic Functions Neurotransmitter imbalances →deficits of executive function and motor control Alerting/arousal system Maintain focus Control of attention and shifting attention Executive function: 6 Major Tasks shifting from one mindset or strategy to another (i.e., flexibility) organization (e.g., anticipating both needs and problems) planning (e.g., goal setting) working memory (i.e., receiving, storing, then retrieving information within short-term memory) separating affect from cognition (i.e., detaching one's emotions from one's reason) inhibiting and regulating verbal and motoric action (e.g., jumping to conclusions too quickly, difficulty waiting in line in an appropriate fashion). ADHD - Etiology Heterogeneous Disorder Multifactorial Etiology: incorporates Genetic Epigenetic Neural Cognitive Behavioral mechanisms (and environmental influences) ADHD - Etiology Behavioral disinhibition = core deficit Difficulties with mobilizing delayed gratification Ability to interrupt ongoing responses Interference control ADHD - Etiology Neurotransmitter(s) imbalance Dominergic & Noradrenergic regulation Thought to increase inhibitory influences Frontal cortical activity influencing subcortical structures Impaired frontal lobe functioning +/or impairment of subcortical connections w frontal lobes Caudate, putamen, globus pallidus (basal ganglia) Effects of Stimulant medication ADHD - Etiology Evidence from Neuroimaging Studies imply structural brain abnormalities in ADHD pts More widespread involvement of brain regions than originally thought: both gray & white matter Smaller volumes in frontal cortex, cerebellum, subcortical structures (caudate, putamen, globus pallidus) Smaller corpus callosum Most consistent finding: differences in inferior cerebellar vermis Cerebellum now being thought to contribute to cognitive fctn (pathways with pons & thalamus), not just motor function fMRI’s show abnormalities of brain activation in frontal-subcorticalcerebellar (fronto-striatal) circuits Casellanos – (NIH) eg, “Developmental trajectories of brain volume abnormalities in children and adolescents w attention-deficit/hyperactivity disorder. JAMA. 2002;288(14)1740-1748 ADHD - Etiology Castellano et al. scanned subjects and controls Four scans over time - ages 5 through 18 Cerebral, cerebellar vermis, caudate, and gray & white matter – all 4 lobes – smaller in ADHD subjects After corrections for total cerbral volume, only cerebellar vermis volume remained statistically smaller. INCIDENTAL FINDING: Unmedicated ADHD subjects showed more white matter loss vs medicated ADHD subjects! ADHD - Etiology Strong Familial Patterns Parents & sibs of proband: 2-8x increased risk Twin studies: >50% chance of being dx with ADHD in second identical twin Associations in families ADHD and human dopamine receptor D4 gene Norepinephrine neurons in locus ceruleus & brainstem nuclei spread throughout brain, but esp in frontal cortex & cingulate gyrus. Next frontier: genomic screening Pharmacogenetics will study effects of specific genotype on medication response Ex: one small study of family w 10-repeat allele of DAT1 showed less vigorous response to MPH. ADHD - Etiology Biological & Psychosocial factors Prenatal exposures Delivery complications Eclampsia Fetal distress Antepartum hemorrhage Postnatal Alcohol Cocaine Nicotine head injuries toxin exposure (lead) heavy marijuana use beginning in early adolescence Environmental marital or family dysfunction Parental psychopathology low social class ADHD – Diagnostic Criteria DSM-IV-TR* Criteria for ADHD – Behaviors associated w Core ADHD Symptoms A. Either (1) or (2) (1)Inattention 6 (or more) of 9 symptoms of inattention Persisted ≥ 6 months Interferes with function (and “to a degree that is maladaptive and inconsistent with developmental level”) *Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Copyright 2000. American Psychiatric Association. ADHD – Diagnostic Criteria Inattention (a) often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities (b) often has difficulty sustaining attention in tasks or play activities (c) often does not seem to listen when spoken to directly (d) often does not follow through on instructions and fails to finish school work, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions) (e) often has difficulty organizing tasks and activities (f) often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (e.g., schoolwork or homework) (g) often loses things necessary for tasks or activities (e.g., toys, school assignments, pencils, books, or tools) (h) is often easily distracted by extraneous stimuli (i) is often forgetful in daily activities ADHD – Diagnostic Criteria (2) Hyperactivity – Impulsivity 6 (or more) of 9 symptoms of HI Persisted ≥ 6 months Interferes with function (and “to a degree that is maladaptive and inconsistent with developmental level”) ADHD – Diagnostic Criteria Hyperactivity (a) often fidgets with hands or feet or squirms in seat (b) often leaves seat in classroom or in other situations in which remaining seated is expected (c) often runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness) (d) often has difficulty playing or engaging in leisure activities quietly (e) is often "on the go" or often acts as if "driven by a motor" (f) often talks excessively Impulsivity (g) often blurts out answers before questions have been completed (h) often has difficulty awaiting turn (i) often interrupts or intrudes on others (e.g., butts into conversations or games) ADHD – Diagnostic Criteria Additional Criteria: B. Some hyperactive-impulsive or inattentive symptoms that caused impairment were present before age 7 years. C. Some impairment from the symptoms is present in two or more settings (e.g., at school [or work] and at home). D. There must be clear evidence of clinically significant impairment in social, academic, or occupational functioning. E. The symptoms do not occur exclusively during the course of a pervasive developmental disorder, schizophrenia, or other psychotic disorder and are not better accounted for by another mental disorder (eg, mood disorder, anxiety disorders, dissociative disorders, or a personality disorder). ADHD – Diagnostic Criteria for Subtypes Core Symptoms of ADHD (Adapted From the DSM-IV-TR) INATTENTION DIMENSION HYPERACTIVITY – IMPULSIVITY DIMENSION INATTENTION HYPERACTIVITY IMPULSIVITY Careless mistakes Fidgety Blurts answers bef questions are completed Difficulty sustaining attention Unable to stay seated Difficulty awaiting turn Seems not to listen Moves excessively (restless) Interrupts/intrudes on others Fails to finish tasks Difficulty engaging in leisure activities quietly Talks excessively Difficulty organizing “On the go” ADHD – Diagnostic Criteria for Subtypes DSM-IV-TR2 criteria define 3 subtypes of ADHD: ● ADHD primarily of the inattentive type 314.00(ADHD/I, having the inappropriately often occurrence of at least 6 of 9 inattention behaviors and less than 6 hyperactive-impulsive behaviors); ● ADHD primarily of the hyperactive-impulsive type 314.01(ADHD/HI, having the inappropriately often occurrence of at least 6 of 9 hyperactive-impulsive behaviors and less than 6 inattention behaviors); ● ADHD combined type 314.01 (ADHD/C, having the inappropriately often occurrence of at least 6 of 9 behaviors in both the inattention and hyperactive-impulsive dimensions). ADHD – Evidence based practice American Academy of Pediatrics published an evidenced based practice guideline for the diagnosis of school-age children with ADHD: American Academy of Pediatrics Subcommitee on Attention-Deficit/hyperactivity Disorder, steering Committee on Quality Improvement and Management. ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of AttentionDeficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics. 2011;128:1158-1022 ADHD – Evidence based practice 1. Evaluate for ADHD for children 4 through 18 years of age presents with academic or behavioral problems and symptoms of inattention, hyperactivity, or impulsivity 2. To make a diagnosis of ADHD, determine that DSM-IV criteria have been met (including documentation of impairment in more than one major setting) Information should be obtained primarily from parents or guardians, teachers, and other school and mental health clinicians involved in the child’s care. also rule out any alternative cause (see DDX below) ADHD – Evidence based practice 3. During evaluation for ADHD, should include assessment for other conditions that may coexist with ADHD emotional or behavioral developmental eg, anxiety, depressive, oppositional defiant, and conduct disorders, eg, learning and language disorders or other neurodevelopmental disorders, physical eg, tics, sleep apnea ADHD – Evidence based practice 4. Recognize ADHD as a chronic condition consider children and adolescents with ADHD as children and youth with special health care needs. Management of children and youth with special health care needs should follow the principles of the chronic care model and the medical home. ADHD – Evidence based practice 5. Recommendations for treatment of children and youth with ADHD vary depending on the patient’s age: a. For preschool-aged children (4–5 years of age), should Prescribe evidence-based parent- and/or teacher-administered behavior therapy as the first line of treatment may prescribe methylphenidate if the behavior interventions do not provide significant improvement there is moderate-to severe continuing disturbance in the child’s function. In areas where evidence-based behavioral treatments are not available, clinician needs to weigh the risks of starting medication at an early age against the harm of delaying diagnosis and treatment (quality of evidence ADHD – Evidence based practice b. For elementary school–aged children (6–11 years of age), prescribe US Food and Drug Administration–approved medications for ADHD and/or evidence-based parentand/ or teacher-administered behavior therapy as treatment for ADHD, preferably both The evidence is particularly strong for stimulant medications and sufficient but less strong for atomoxetine, extended-release guanfacine, and extended-release clonidine (in that order) The school environment, program, or placement is a part of any treatment plan. ADHD – Evidence based practice c. For adolescents (12–18 years of age), prescribe Food and Drug Administration–approved medications for ADHD with the assent of the adolescent may prescribe behavior therapy as treatment for ADHD preferably both. 6. The clinician should titrate doses of medication for ADHD to achieve maximum benefit with minimum adverse effects ADHD – Evidence based practice Many of the treatment guidelines based on MTA (Multimodal Therapy of ADHD) studies: A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children With ADHD. Arch Gen Psychiatry. 1999;56(12):1073–1086 Jensen P, Hinshaw SP, Swanson JM, et al. Findings from the NIMH multimodal treatment study of ADHD (MTA): implications and applications for primary care providers. J Dev Behav Pediatr. 2001;22(1):60–73 ADHD – Evidence based practice MTA Study results Positive effects of behavior therapy when combined with medications. Most studies that compared behavior therapy to stimulants found a much stronger effect on ADHD core symptoms from stimulants than from behavior therapy. The MTA study found that combined treatment (behavior therapy and stimulant medication) was not significantly more efficacious than treatment with medication alone for the core symptoms of ADHD after correction for multiple tests in the primary analysis. A secondary analysis of a combined measure of parent and teacher ratings of ADHD symptoms revealed a significant advantage for the combination with a small effect size. The combined treatment compared w meds alone offered greater improvements on academic & conduct measures when ADHD coexisted with anxiety and for children in low SEC environments. Parents & teachers more satisfied with treatment plan for combined therapy. Combo of medication management & behavior therapy facilitated a lower dose of stimulants, possibly reducing risk of side effects. ADHD – Diagnostic Considerations Preschool Children Adolescents ADHD – Differential Diagnosis Bipolar disorder Anxiety disorder Depression Absence seizures Visual or hearing impairments Learning disabilities and processing problems Medication – Phenobarbital, antihistamines, anticonvulsants Chaotic environment or classroom; Inadequate teacher, neglect or abuse -bullying Giftedness Pain syndromes Endocrine, metabolic disorders. Anemia, thyroid abnormalities. Lead. Drugs or alcohol Language problems Sleep disorder (apnea) Psychosis ADHD: Co-Morbid Conditions Externalizing Internalizing ODD (30-60%) and conduct disorder (10-50%) Intermittent explosive disorder Anxiety disorder (10-30%) Depression mood disorder including bipolar Associated Motor Deficits Clumsiness, poor motor planning, handwriting and fine motor difficulties and coordination problems. Difficulty with utensils ADHD: Co-Morbid Conditions Associated Motor Deficits Clumsiness poor motor planning handwriting and fine motor difficulties coordination problems Proprioception Ex: Difficulty with utensils ADHD: Co-Morbid Conditions Associated Speech & Language Deficits Early delays in speech/language acquisition Persistent speech/language disorders Common to ADHD and learning disabilities receptive and expressive language deficits weaknesses in pragmatic language skills Impairment in auditory processing – common in children w ADHD Auditory processing disorder (APD): deficit in the processing of auditory information despite normal hearing. Individuals with APD typically have difficulty listening in the presence of background noise, understanding rapid or degraded speech, and following oral instructions. Recent investigations suggest a dysfunction of auditory working memory. ADHD: Diagnostic Evaluation Family (parents, guardian, other frequent caregivers): Chief concerns History of symptoms (eg, age of onset and course over time) Family history Past medical history Psychosocial history Review of systems Validated ADHD instrument Evaluation of coexisting conditions Report of function, both strengths and weaknesses ADHD: Diagnostic Evaluation School (and important community informants): Concerns Validated ADHD instrument Evaluation of coexisting conditions Report on how well patients function in academic, work, and social interactions Academic records (eg, report cards, standardized testing, psychoeducational evaluations) Administrative reports (eg, disciplinary actions) ADHD: Diagnostic Evaluation Child/adolescent (as appropriate for child’s age and developmental status): Interview, including concerns regarding behavior, family relationships, peers, school For adolescents: validated self –report instrument of ADHD and coexisting conditions Report of child’s self-identified impression of function, both strengths and weaknesses Clinician’s observations of child’s behavior Physical and neurologic examination ADHD: Diagnostic Evaluation Physical Examination r/o findings that cld mimic ADHD or syndromes with a high prevalence of ADHD behaviors Visual acuity Audiogram Ht, Wt, HC, BP Neurologic examination, expanded Look for dysmorphic features (r/o FAS, FRAX) Full or abbreviated neurodevelopmental screening tasks Look for LD, language d/o, May notice s/s of hyperactivity and/or inattentiveness resulting from stress of tasks ADHD: Diagnostic Evaluation TASK FUNCTION Ask child to write a sentence Written expression & dysgraphia Ask child to tell about a movie or video seen recently Oral expression, memory, sequencing Ask child to read a paragraph Reading fluency & comprehension appropriate for age (e.g., Grey Oral Reading Test) Ask child to repeat a series of random numbers: both forward & reverse Attention, short-term memory, sequencing, working memory Ask child a multiple-step task to complete Attention, memory, auditory processing in order given ADHD: Treatment Medication & Behavior Therapy (eg, results of MTA studies) Consider specific target outcomes to guide management Reflect the key symptoms of that child and specific impairments Sample target outcomes – Complying w parental commands at home Finishing homework and handing it in. ADHD: Treatment Medications: Most widely prescribed are the psychostimulants: considered first line Methylphenidate preparations Amphetamine preparations Short Acting (3-6 hours) Intermediate acting (6-8 hours) Long acting (10 – 12 hours) ADHD: Treatment Appropriate initiation and follow-up Initial counseling & education Start w low dose Follow weekly at first Titrate dose Periodic follow-up behavior assessment (parent & school staff) Switch to another stimulant or formulation, if necessary Determine the reason for treatment failure ADHD: Treatment Methylphenidate (mph) preparations Amphetamine Preparations Amphetamine Preparations Non-Stimulants Atomoxetine (Strattera) Tricyclic antidepressants Imipramine, desipramine, nortriptyline Inhibite NE reuptake Limited by cardiac side effects Bupropion (Wellbutrin and others) Antidepressant with NE & DA properties Non-Stimulants Alpha-2 adrenergic agonists Clonidine Long acting = Kapvay Guanfacine Long acting = Intuniv Second-line preparations for ADHD Can be used to counteract stimulant SE’s For children with co-morbid aggressive behaviors Guanfacine can be used for children with ADHD, tics, aggression. Management of Side Effects Complementary and Alternative Therapies Omega-3 fatty acid supplementation Melatonin Others: encourage parents to report what they are using at home