Attention Deficit Hyperactivity Disorder Royann Mraz, MD Clinical Associate Professor Center for Disabilities and Development Dec 10, 2014

No conflict of interest

Epidemiology of ADHD 8-10% of school aged children 8% 4-10yr, 14% 11-17 yr. Boys>Girls 2-4:1 High rates of Co-Morbidities –especially psychiatric and learning 33% have one co-morbidity, 16% -2, 18% - 3

Neurobiology of ADHD Cerebellar-prefrontal-striatal network hypothesis Volume differences- caudate, smaller cerebrum (esp. anterior) and cerebellum

Genetics Genetic imbalance in dopamine and noradrenergic systems- several genes play a role Strong genetic influence Concordance -92% identical twins, 33% dizygotic twins

Environment Increased risk with prenatal smoking exposure * Prematurity, Brain injury, fetal alcohol, lead Dietary factors do not play a role in the majority of children – food additives, essential fatty acids?, Fe or Zn deficiency?

Attention Deficit Hyperactivity Disorder- subtypes Predominately inattentive type – 8-9 yr Pr Predominately inattentive type Predominately hyperactive-impulsive- start at 4yr, max 6-8 yr Combined type- most common

DSM 5 ADHD Children - 6/9 symptoms of Inattention (inconsistant with developmental level, impacts activities, and not secondary to oppositional behavior or failure to understand) and/or 6/9 symptoms of hyperactivity/impulsivity Adolescent and adults – only require 5 symptoms from either category Some symptoms must be present by 12 years of age (DSM-IV by 7 yrs and be impairing)

Diagnostic criteria - Inattention Careless mistakes Difficulty sustaining attention Does not seem to listen Does not follow through on tasks Not organized Avoids sustained mental effort Loses things Is easily distracted If forgetful 6/9

Diagnostic criteria – Hyperactivity/Impulsivity Fidgets or squirms Inappropriately leaves seat Inappropriately runs or climbs Has difficulty playing quietly Is “on the go” Talks excessively Blurts out answers Has Difficulty waiting his or her turn Interrupts or intrudes on others 6/9

DSM-5 ADHD updates Most of changes recognize that ADHD is a chronic illness and help with diagnosis in adolescents and adults 18 symptoms remain the same (additional examples provided) Inattentive symptom f: Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (eg. Schoolwork or homework; for older adolescents and adults, preparing reports, completing forms, reviewing lengthy papers)

ADHD Updates Cross-situational symptoms rather than impairment Symptoms interfere or reduce quality of social, academic, or occupational functioning Present for over 6 months Symptoms aren’t secondary to other mental disorder Rate current severity of symptoms –mild, moderate, severe

Consequences of DSM-5 ADHD Easier to diagnose in adolescents and adults May increase the prevalence rates Can diagnose ADHD in individuals with Autism Spectrum disorder

Differential Diagnosis of ADHD Normal age appropriate behavior, Unrealistic expectations Lack of structure/limits Family stress and dysfunction, abuse PTSD, RAD, and adjustment disorders Intellectual disability/Learning disorder Autism, fetal alcohol, seizures, lead exposure, sleep disorder, thyroid

COMORBIDITY Learning disorder 10-30% Opposition defiant disorder/ Conduct disorder 50-67% Anxiety or Mood disorder 30% Tourette’s and tic disorders Coordination problems Substance abuse Sleep problems

DIAGNOSTIC EVALUATION Child’s history and functioning Family history and functioning School information Rating scales – parent and teacher Interview and physical exam of child Consider psychological/educational evaluation

AAP Practice Guidelines for ADHD 2011 Initiate evaluation for ADHD in child 4-18 years of age if behavior or academic problems and ADHD symptoms Determine if DSM criteria are met in more than one setting (teacher questionnaires) and rule out other causes

AAP guidelines for ADHD Assess for co-existing conditions – Emotional/behavioral (anxiety, depression, ODD, conduct disorders) Developmental (learning, language, etc.) Physical (sleep apnea, tics, etc.)

AAP Guidelines for ADHD Treat ADHD as a chronic condition using principles of chronic care model and medical home Titrate medication to achieve maximal benefit with minimal side effects

AAP guidelines for preschoolers Addresses evaluation and management of 4 and 5 year olds with ADHD symptoms Recommends behavior management counseling and placement in structured setting Allows for stimulant treatment if above isn’t sufficient

AAP Guidelines ADHD 6-11 Years Treat with FDA approved medication (strong evidence for stimulants) and/or Parent and/or Teacher behavior management or preferably both 12-17 Years Treat with FDA approved medication May prescribe behavior therapy

Consider referring if Preschool child Developmental delay or learning problems ADHD, inattentive type Family dysfunction Moderate to severe behavior problems Anxiety or depression

Medical Treatment of ADHD Monitor or treat co-morbidities Educate patient and family Set goals with family and school ADHD is a chronic disorder – 65% of children with ADHD will have symptoms as adolescents

Medical Management of ADHD Medication is most effective treatment Good behavior management program can provide additional benefit Stimulants are first line treatment and most effective 70-80% of children will respond to a stimulant

Stimulants Methylphenidate, d-amphetamine, mixed amphetamine salts are equally effective Probably act by increasing dopamine and norepinephrine levels Similar side effects

Stimulants Individualized dosing- often have better results with higher dose All day coverage for many/most children Frequent follow-up with health care provider with teacher feedback If one stimulant doesn’t work, try another

Stimulants Improve attention span Decrease hyperactivity and impulsivity Improve work completion Often improve behavior Often improve academic performance

Common stimulant side effects Decreased appetite- give with or after meals Difficulty falling to sleep Tics Stomachaches – give with food Headaches

Less common side effects Moodiness or irritability Overly quiet “Zombie effect” Weight loss Small decrease in height velocity Rebound symptoms as med wears off Mild increase in heart rate and B/P Rare risk of mania or hallucinations Priapism- 15 cases reported

Stimulants Methylphenidate products (Ritalin, Concerta, Metadate, Methylin, generics, patch D-methylphenidate (Focalin, Focalin XR) D-amphetamine (Dexedrine, Dextrostat) Mixed amphetamine salts (Adderall, Adderall XR)

Methylphenidate –dose and duration of action Short acting ( Ritalin, Methylin, etc.) 3-5 hrs (.3-.7 mg/kg/dose 2-3 times/day) D-methylphenidate Focalin(.15-.3 mg/kg/dose) Intermediate acting (Ritalin SR, Metadate ER, Methylin ER) – 3-8 hr Extended release ( Metadate CD, Ritalin LA) 6-8 hr, Concerta-10-12 hr Methylphenidate patch, wear for 9 hr Usual maximum daily dose – 2 mg/kg

Methylphenidate Extended Release Concerta – longest lasting,22% immediate release, ascending plasma level, must be swallowed whole Ritalin LA 50% immediate release, 50% release at 4 hr, mimic bid dosing. Can open capsule Metadate CD 30% immediate release, can open capsule

Methylphenidate patch Methylphenidate patch (Daytrana) 10,15,20,30 mg patches Takes 2 hrs to take effect, wear 9 hours, lasts 12 hours Same side effects, patch may come off Useful for patients unable to take pills or with fast metabolism

Amphetamines – dose and duration of action Short acting (Dexedrine, Dextrostat) – 4-6 hr Intermediate acting (Adderall, Dexedrine spansules) 5-8 hr Extended release (Adderall XR) 10-12 hr Usual maximum daily dose – 1 mg/kg Dose is ½ to 2/3 of methylphenidate dose

Other stimulant preparations. Lisdexamfetamine (Vyvanse) Pro-drug, which is activated when aminoacid is cleaved off Effective for ADHD, same side effects Aim is to provide protection against abuse and addiction 6-12 years, start at 20-30 mg, can increase weekly up to 70 mg max Lisdexamfetamine 30 mg roughly equivalent to dextroamphetamine 10 mg

Cardiac warnings 27 unexplained deaths in children under 18 yrs on ADHD medication reported between 1992-2004 11 on methylphenidate 13 on amphetamine salts (Adderall) 3 on atomoxetine (Strattera) FDA recommends not using if heart disease, arrhythmia, or FH of arrhythmia Concern about patients with undiagnosed heart disease and long term effects EEG not needed if cardiac hx is negative

Benefits of stimulants in Adolescents Medication reduces risk of auto accidents for ADHD patients Medication reduces risk of substance abuse in ADHD patients

Other Medications for ADHD Atomoxetine (Strattera) Bupropion (Wellbutrin), imipramine Alpha2 agonists -clonidine or guanfacine (Tenex) – useful for tics, sleep, and aggression

Atomoxetine (Strattera) Selective norepinephrine reuptake inhibitor Effective for ADHD, may take 3-4 weeks to see full effect No abuse potential, not controlled substance Unlikely to worsen tics or anxiety Dosage – start .5 mg/kg/day for 3 days, then up to 1.2 to 1.4 mg/kg/day 10, 18, 25, 40, 60, 80, 100 mg capsules Useful for ADHD with anxiety or depression

Atomoxetine (Strattera)- side effects Somnolence – can give in evening or divide dose Anorexia, GI upset, weight loss – give with food, divide dose Dizziness Rare risk of liver disease Increased risk of suicidal ideation .4%

Alpha 2 Agonists Clonidine and guanfacine (Tenex) Adjuctive medication Useful for sleep, tics, aggression, hyperarousal Not as effective for inattention May take 2 weeks to see effect

Alpha 2 Agonists Clonidine .003-.01 mg/kg/day, tid,qid, often start .025 - .05 mg per day, also available as patch and long-acting form Guanfacine .04-.08 mg/kg/day, max 4 mg/day, often start .5 mg perday (also once daily form ) Side effects – sedation, especially with clonidine, dry mouth, depression, low B/P, headache Withdrawal symptoms if stopped suddenly –high pulse, B/P, headache, agitation

ADHD and Co-morbidities ADHD and anxiety – respond to stimulants, may need to add SSRI, another option is atomoxetine ADHD and tics – stimulants and clonidine or other meds for tics, atomoxetine ADHD and aggression – stimulant and clonidine/guanfacine or other meds

Parenting and ADHD Brief clear instructions Give immediate and frequent feedback and consequences Use incentive more than punishment Try to be consistent and provide structured environment Plan for problem situations Negotiable and non-negotiable issues

Special Education and ADHD Child with ADHD may be eligible for special education, under “Other health impairment” Child must be tested and qualify for special education “Limited alertness” for academics, which adversely affects education, including grades, tests, behavior, social skills.

504 Plan Section 504 of Rehabilitation Act Schools receiving Federal funds and employers can not discriminate against people with disabilities (including ADHD) and must make reasonable accommodations

Educational Accommodations Tailor homework assignments and tests Structured environment, help with organization Simplify and/or provide visual instructions Behavior management techniques Use of tape recorders or notes Daily or weekly report to parents

Medical management for ADHD Stimulants are first line treatment 70-80% effective Titrate to optimal dose All day coverage for many/most children Set and monitor goals Close long-term follow-up

References AAP. ADHD Clinical Practice Guidelines. Pediatrics 2011;128: 1007-1022. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Ed.,2013, American Psychiatric Association, Arlington, VA.

Resources www.chadd.org www.dbpeds.org www.aap.org www.help4adhd.org www.ParentsMedGuide.org www.aacap.org www.nichq.org ADHD toolkit

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