4/5/17 Conflicts of Interest ADHD: Management Update I have no conflicts to disclose. Jennifer R. Walton, MD, MPH, FAAP April 7, 2017 ADHD: DSM-5 Definition Objectives To briefly review ADHD diagnostic criteria To review the indication for treatment and types of treatment for Attention/Deficit/Hyperactivity Disorder To discuss the types of medications used to treat ADHD and monitoring their management Persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development Symptoms present for at least 6 months Symptoms causing impairment present before age 12 years Impairment in two or more settings Clear evidence of impairment in social, academic, or occupational functioning Symptoms not explained by another disorder Subtypes AD/HD, Combined type AD/HD, Predominately inattentive type AD/HD, Predominately hyperactive-impulsive type ADHD DSM Criteria: Inattention ADHD DSM Criteria: Hyperactivity Fails to give close attention to details, makes careless mistakes Difficulty sustaining attention in tasks or play Does not seem to listen when spoken to directly Does not follow instructions or complete work Difficulty organizing tasks and activities Avoids/ dislikes tasks requiring mental effort Loses things necessary for tasks or activities Easily distracted Often forgetful Fidgets or squirms in seat Leaves seat when expected to stay in it Runs or climbs excessively Difficulty playing quietly Often on the go, acts as if driven by a motor Talks excessively Blurts out answers before question completed Difficulty awaiting turn Interrupts or intrudes on others 1
ADHD: Associated Problems Oppositional Defiant or Conduct Disorder: 67% Social Problems/Peer Rejection: 50% Learning Disabilities: 25-50% Anxiety Disorders 20-30% Depression: 10-25% Rule-out Alternative Causes of Core ADHD Symptoms: Seizure disorders Hypo or hyperthyroidism Sleep disorders Tourette s Syndrome Hearing or visual impairment Medication side effects Brain Injury (infectious, traumatic, metabolic/ toxic) Developmental/Educational Learning disabilities Intellectual Disability Pervasive Developmental Disorders Psychiatric Mood or anxiety disorders Psychosocial Ashley is an 8 year old girl referred for an ADHD evaluation. Her mother describes problems with inattention both at home and at school. She is in 2nd grade and is struggling in school. Her teacher notes that she just doesn t pay attention. She has trouble sitting still and often disrupts the classroom. Her family is concerned that these issues are interfering with her school performance. Ashley has also missed several days of school this year for stomach pains and headaches. Her mother has recently taken a new job, and these absences have been difficult for her family to manage. They would like to get Ashley started on ADHD medication to help her in school and reduce family stress. Assessment Process AAP. Pediatrics. 2011. Presence of DSM-V Criteria Evidence of Impairment Behavioral rating scales Clinician judgment Vanderbilt Rating Scales Inattention Hyperactivity/Impulsivity Parent Teacher Total symptom score 46 36 ODD Screen Conduct Disorder Screen Anxiety/Depression Screen # Areas with Impairment 3 2 Average Performance Score 3.5 3 2
Evidence Based Therapies for ADHD Educational Interventions ADHD is a chronic condition Behavioral Counseling Environmental Accommodations Motivational Systems Identify target outcomes Medications (monitor treatment response systematically) Stimulant Medications Norepinepherine Reuptake Inhibitors Alpha 2 Adrenergic Agonists ADHD Treatment: MTA Study 579 Subjects 6 sites Methylphenidate: Placebo, 5,10, 15, 20 mg Behavioral Treatment Combined Treatment Community Treatment Multimodal Treatment of ADHD (MTA) Study % normalized after 18 months Swanson. J Am Acad Child Adolesc Psychiatry. 2001. MTA Key Points What treatment was most effective? Intensive behavioral intervention combined with medication was similar to medication alone How did community providers differ? Community providers tended to use Lower doses (22.6 vs. 37.7mg/day) More medications (10% on two drugs by study end) Who did behavioral therapy help the most? Behavioral therapy was most beneficial for children with oppositional behavior Jensen, et al. J Dev Beh Pediatr. 2001;22:(1):60-73 ADHD: AAP Treatment Guidelines Pediatrics 2001;108:1033-1044 Recommended treatments should include stimulant medication and/or behavioral therapy Medication alone normalizes function in only 38% of children No differences between different stimulants except in duration of action Stimulant medication dosage usually not weight dependent The first dose that a child responds to may not be the best dose to improve function Texas Children s Medication Algorithm J Am Acad Child Adolesc Psychiatry 2006:45:642-657 Stage 1 MPH or Amph Stage 2 S2mulant not used in Stage 1 Stage 3 Stages 4-6 Atomoxe2ne Others S2mulant & Atomoxe2ne 3
ADHD Medications Stimulant Medication Mechanism of action Block reuptake of norepinephrine and dopamine Enhance norepinephrine and dopamine activity in the prefrontal cortex Enhance dopamine activity in the basal ganglia Stimulant Effects Improved Vigilance Attention to task Reaction time Impulse control Fine motor control Academic productivity and accuracy Decreased Fidgeting Activity level ADHD: Stimulant Side Effects Common Decrease appetite Headaches/stomachaches Insomnia Less frequent Rebound effects Tics Dysphoria, irritability, social withdrawal Rare Growth suppression, bone marrow suppression, psychosis Methylphenidate Start low, reassess, and go up if needed Start at 5 or 10mg/day Increase 5-10mg/day every 1-2 weeks if limited benefits and adverse effects Consider short acting afternoon dose if needed www.ohiomindsmatter.org Adapted from AACAP. J Am Acad Child Adolesc Psychiatr. 2007;46;89-921. Methylphenidate Formulations Short acting ~ 4hrs Ritalin, Methylin, Metadate Focalin Intermediate ~ 6-8 hrs Methylin ER, Metadate ER, Ritalin SR Long acting ~ 8-10 hrs: Metadate CD (30:70), Ritalin LA ~ 10-12 hrs: Concerta (30:70), Focalin XR (50:50), Daytrana (patch) 4
Methylphenidate Titration Maximum FDA dosing per day (off-label) Ritalin, Methylin, Methylin ER, Metadate ER, Ritalin SR, Metadate CD, Ritalin LA 60mg (100mg for >50kg) Concerta 72mg (108mg) Focalin 20mg (50mg); Focalin XR 30mg (50mg) Daytrana 30mg (?) Quillivant (?) Adapted from AACAP. J Am Acad Child Adolesc Psychiatr. 2007;46;89-921. Methylphenidate Other considerations Many long acting forms can be opened and sprinkled on applesauce or pudding Metadate CD, Ritalin LA, Focalin XR Concerta capsule cannot be opened due to delivery system Daytrana patch is applied at the hip; may cause skin irritation Quivillant XR is an extended release liquid and Quillichew a chewable extended release tablet Aptensio XR is an extended release capsule 12 hour duration; two peaks (2 and 8 hours) 10, 15, 20, 30, 40, 50, and 60mg Amphetamine Start low, reassess, and go up if needed Start at 5-10mg/day Increase 5-10mg/day every 1-2 weeks if limited benefits and adverse effects www.ohiomindsmatter.org Adapted from AACAP. J Am Acad Child Adolesc Psychiatr. 2007;46;89-921. Amphetamine Formulations Short acting: ~4 hrs Dexedrine, dextrostat (d-amphetamine) Intermediate: ~6-8 hrs Adderall (amphetamine salts) Dexedrine Spansule (d-amphetamine) Long acting: ~10-12 hrs Adderall XR (50:50), Dexedrine Spansule (50:50) Vyvanse (lisdexamphetamine) Amphetamine Titration Maximum FDA dosing per day (off-label) Dexedrine, Dextrostat, Adderall, and Dexedrine spansule 40mg/day (60mg if >50kg) Adderall XR 30mg (60mg if >50kg) Vyvanse 70mg (?) Adapted from AACAP. J Am Acad Child Adolesc Psychiatr. 2007;46;89-921. Amphetamine Other considerations Adderall XR and Dexedrine spansule can be opened and sprinkled Vyvanse capsule can be opened and contents dissolved in small amount of water (1-2 tsp) and may have decreased abuse potential due to pro-drug delivery system Procentra is an immediate release dextroamphetamine liquid; Zendedi is an immediate release dextroamphetamine tablet Evekeo is an immediate release 50:50 mix of l- and d- amphetamine 5
How to Choose a Long-Acting Stimulant How long do you want it to work? Can the child swallow a pill? Do you want a methylphenidate or d-amphetamine type? Insurance company formularies Minimizing side effects Decrease the dose or duration of action Stimulants: Long-Acting Technology Wax Matrix (Metadate ER, Methylin ER, Ritalin SR) delayed onset of action, variability in duration of action Osmotic (Concerta) must swallow whole Beads (Adderall XR, Focalin XR, Ritalin LA, Metadate CD) can sprinkle Patch (Daytrana) Delayed onset of action, can vary duration based on when you remove patch Hepatic Metabolism (lisdexamfetamine) Less individual variability in time to maximum drug concentration and half-life ADHD in Preschoolers Methylphenidate is effective in treating ADHD in preschoolers with moderate-severe dysfunction No effect at 1.25mg TID Significant difference at 2.5mg TID Mean optimal dose ~15mg/day Preschoolers experience more side effects Dextroamphetamine is FDA approved for children < 6 years Stimulants vs Atomoxetine Stimulants Advantages More effective for school Can give only on school days Disadvantages Appetite suppression and insomnia common May exacerbate tics Can exacerbate or improve anxiety Atomoxetine (Strattera) Advantages May work in evening and early morning No abuse potential Less likely to exacerbate tics May improve anxiety Disadvantages Must take daily Stomachaches if not given with food Can increase suicidal ideation Longer time to onset of action Atomoxetine (Strattera) Side effects N/V, fatigue, decreased appetite, dizziness, constipation, irritability, rash Initiate dosing at 0.5 mg/kg/day Maintain this dose for 1 week FDA approved to 1.4 mg/kg/day (max 100 mg) Once daily dosing possible More chance of fatigue/nausea than with BID dosing Alpha-Adrenergic Agonists Mechanism of action Theoretically acts on post-synaptic receptors in the prefrontal cortex Other considerations Sedation: Clonidine >> Guanfacine Short acting Clonidine can be helpful for delayed sleep onset Rebound hypertension may occur if dose stopped abruptly Must give daily 6
Alpha- Adrenergic Agonists Start low, reassess, and go up if needed Guanfacine (Intuniv ) Long acting: start at 1mg qd; increase weekly to 4mg maximum dose Clonidine (Kapvay ) Long acting: start at 0.1mg qhs; increase weekly by 0.1mg divided BID to 0.4mg/day maximum dose Monitor for sedation, hypotension, and bradycardia Update on Ashley Ashley is prescribed Concerta 18mg each morning. At one week, no side effects are noted, but no benefits are seen. Concerta is increased to 27mg. At one month, Ashley is seen for a follow up visit. She is now taking 36mg each morning after another dose increase. Vanderbilt questionnaires are available for your review. Vanderbilt Rating Scales Inattention Hyperactivity/Impulsivity Parent Teacher Total symptom score 46 38 36 20 ODD Screen Conduct Disorder Screen Anxiety/Depression Screen # Areas with Impairment Average Performance Score ANY IDEAS? FAQ Why are you prescribing stimulants for hyperactivity, isn t that counter-intuitive? The medication isn t working, can we try a different one? Are there any natural ways to treat ADHD without medications? Is he going to be on this forever? Does ADHD go away? Is he going to get addicted to the medications? Common Medication Questions on Side Effects Decreased Appetite? Give medication with or shortly after meals. Offer high calorie foods when hungry Encourage eating after school and/or before bedtime Difficulty falling asleep? Try 8 hour instead of 12 hour medication Melatonin If hyperactive in afternoon can give short acting Common Medication Questions on Side Effects? Dazed and/or withdrawn behavior? Reduce dosage or discontinue medication and try a different class Gradual return of hyperactive behavior? Increase dosage. Be sure it s not rebound behavior 7
Summary Primary Care Providers often the first professional to evaluate a child for ADHD Stimulant medications are the single most effective treatment for ADHD and can be managed in primary care Attend to diagnostic accuracy Start low, then titrate based on symptom reduction and adverse effects Maximize the use of one medication before adding another or switching medications Be systematic about monitoring treatment response Acknowledgements Rebecca Baum, MD Nathan Blum, MD Anson Koshy, MD, MBE Mary Pipan, MD Catherine Riley, MD Kimberlly Stringer, MD, MPH References AACAP. J Am Acad Child Adolesc Psychiatr. 2007;46;89-921 Bauer NS, Webster-Stratton C. Prevention of behavioral disorders in primary care. Curr Opin Pediatr. 2006;18:654-60. Inattention, Hyperactivity, Impulsivity. Ohio Minds Matter, Copyright 2013, Ohio Medicaid. Attention Deficit/Hyperactivity Disorder. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. American Psychiatric Association, American Psychiatric Publishing, Inc. May 2013. FDA permits marketing of first brain wave test to help assess children and teens for ADHD. FDA News Release; U.S. Food and Drug Administration, FDA and U.S. Department of Health and Human Services, released 7/15/2013, accessed August 22, 2013. http:// www.fda.gov/newsevents/newsroom/pressannouncements/ucm360811.htm Prock L, Rappaport L. Attention and Deficits of Attention. Developmental-Behavioral Pediatrics, Fourth Edition. Saunders of Elsevier, Inc. 2008. Greenberg, D. ADHD. DBP-PREP 2012. Greenhill L, Kolllins S, Abikoff H et al. Efficacy and safety of immediate-release methylphenidate in preschoolers. J Am Acad Child Adolesc Psychiatr. 2006;45:1284-93. Greenhill LL, Posner K, Vaughan BS, et al. Attention Deficit Hyperactivity Disorder in preschool children. Child Adolesc Psychiatric Clin N Am. 2008;17:347-66. Murray DW. Treatment of preschoolers with Attention-Deficit/Hyperactivity Disorder. 2010;12:374-81. Posner K, Melvin GA, Murray DW, et al. Clinical presentation of Attention-Deficit/Hyperactivity Disorder in preschool children: the Preschoolers with Attention-Deficit-Hyperactivity Treatment Study (PATS). J Child Adolesc Psychopharmacol. 2007;17:547-562. Smidts D, Oosterlaan J. How common are symptoms of ADHD in typically developing preschoolers? A study on prevalence rates and prenatal/ demographic risk factors. Cortex. 2007;43:710-17. Stahl SM. The Prescriber s Guide. 3rd ed. New York, NY: Cambridge Press; 2009:103-104,233-235. Subcommittee on Attention-Deficit/Hyperactivity Disorder; Steering Committee on Quality Improvement and Management. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2011; 128:1007-22. Swanson. J Am Acad Child Adolesc Psychiatry. 2001 8