Pediatric ADHD: Focus on Pharmacotherapy - cdn. ¢â‚¬â€œPharmacotherapy is rejected ¢â‚¬¢Pharmacotherapy is

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  • Pediatric ADHD: Focus on Pharmacotherapy

    Handout for the Neuroscience Education Institute (NEI) online activity:

  • Learning Objectives

    • Define the different types of stimulant medications

    commonly used in children with ADHD

    • Discuss the longer-term effects of ADHD treatment

    • Identify controversial adverse events related to the

    treatment of ADHD

    • Discuss the spectrum of medications evaluated for

    the treatment of ADHD in children

    Copyright © 2014 Neuroscience Education Institute. All rights reserved.

  • ADHD Overview

    • Prevalence: 6-8% of children worldwide; 4% of adults

    • Considered a chronic disorder; ~50% persistence into adulthood

    • Associated with substantial impairment

    – Academic, occupational

    – Social, interpersonal

    – Injuries, motor vehicle accidents, high-risk behaviors

    • Multimodal treatment planning

    • Pharmacological treatment is fundamental

    Faraone, et al. World Psychiatry. 2003; Kessler, et al. Am J Psychiatry. 2006;

    American Academy of Pediatrics Guidelines. 2002; AACAP Guidelines. 1997;

    Wilens, Spencer. Postgrad Med. 2010; Biederman, et al. Pediatrics. 2010.

  • Heritability of ADHD

    Faraone SV et al. Biol Psychiatry. 2005;57(11):1313-1323; Hettema JM et al. Am J

    Psychiatry. 2001;158(10):1568-1578; Cardno AG, Gottesman II. Am J Med Genetics.

    2000;97(1):12-17; Ronald A et al. Eur Child Adolesc Psychiatry. 2008;17(8):473-483;

    Silventoinen K et al. Twin Res. 2003;6(5):399-408.

    Heritability of ADHD between 0.9 and 1.0 Willcutt, 2000; Levy, 1997; Gillis, 1992

    Heritability of ADHD between 0.8 and 0.9 Coolidge, 2000; Thapar, 2000; Thapar 1995

    Heritability of ADHD between 0.7 and 0.8 Rietveld, 2003; Martin, 2002; Sherman, 1997; Gjone, 1996;

    Stevenson, 1992; Willerman, 1973; Matheny, 1971

    Heritability of ADHD between 0.6 and 0.7 Kuntsi, 2001; Hudziak, 2000; Nadder, 1998; Silberg,

    1996; Schmitz, 1995; Edelbrock, 1992; Goodman, 1989

    Autistic-like traits: 0.82-0.87 Schizophrenia: 0.8-0.85

    Mean heritability of

    ADHD: 0.75

    Panic disorder: 0.43







    Height: 0.89-0.93

  • For review, see: Johansen EB, et al. Behav Brain Functions. 2009;5:7.

    Suspected Neurochemical Pathophysiology of ADHD

  • ADHD Assessment • Life history (with information from parents and teachers or

    school records, if available for adolescents)

    • Self-report for (adolescents) adults

    • Mental status exam

    • Rating scales: measuring core and broad features

    • Medical history review, cardiac and neurological status, blood


    • If medical history is unremarkable, laboratory or neurological

    testing is not indicated

    • Assess for comorbidity (psychiatric, cognitive, psychosocial,


    Pliszka S; AACAP Work Group on Quality Issues.

    J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921.

  • Essential Features of ADHD Symptoms

    • Inattention: 6 (5 in adults) or more developmentally inappropriate


    • Hyperactivity/impulsivity: 6 (5 in adults) or more developmentally inappropriate


    • Present before age 12 years

    • >6 months persistence

    • Not better accounted for by another disorder

    • Impairment

    – Clear evidence that symptoms interfere with or reduce the quality of functioning

    – Several symptoms in at least 2 settings (eg, school, social, work)

    • Subtypes: combined, predominately inattentive or hyperactive/impulsive

    APA. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA:

    American Psychiatric Publishing; 2013.

  • Main Changes to ADHD in DSM-5

    • Similar symptoms (eg, 9 symptoms of inattention and/or

    hyperactivity-impulsivity); more prompts added

    • Change in symptom requirements

    – 17 years: 5/9 hyperactivity-impulsivity and/or 5/9 inattention

    • Change in symptom onset: prior to age 12 years

    • Change in "clinically significant impairment" to relative


    • Change in exclusion: diagnosis can be made in autism

    spectrum disorder

  • Consequences of Not Treating ADHD in Teens

    • Academic failure or underachievement

    • Low self-esteem

    • Increased risk of later antisocial behavior – Delinquency

    – Aggression/fighting

    – Legal consequences

    • Risk-taking behavior – Motor vehicle accidents

    – Substance use

    – Promiscuity

    – Accidental deaths, suicides, suicide attempts

  • Age-Dependent Decline of ADHD Symptoms

    Biederman J, et al. Am J Psychiatry. 2000;157(5):816-818.








  • Developing a Treatment Plan • Educational evaluation and planning is critical

    • Parent support and guidance (referral to support groups,

    CHADD, ADDin)

    • Behavior therapy may be recommended initially if:

    – ADHD symptoms are mild to moderate

    – Patient is in preschool

    – Pharmacotherapy is rejected

    • Pharmacotherapy is typically considered first line

    • Once treatment is established, practitioner's role:

    – Coordinate with school or college student health services regarding ADHD treatment

    – Prepare patient (and family) for major transitions

    Pliszka S; AACAP Work Group on Quality Issues. J Am Acad Child Adolesc Psychiatry.

    2007;46(7):894-921; CADDRA Canadian ADHD Practice Guidelines.

    Accessed June 18, 2014; Larry Culpepper, MD, MPH. Email communication. January 16, 2009.

  • • Data suggest that enhanced activity improves general attentiveness and executive functioning in children

    – ABC program

    – Less use of asthma and ADHD medication

    • Activity throughout the day reduces hyperactivity

    • Activity improves frontal lobe function (on fMRI)

    • Preliminary mild improvements shown in ADHD (executive functioning Cronbach's alpha .3)

    ABC=activity bursts in the classroom.

    Katz DL, et al. Preventing Chronic Dis. 2010;7(4):A82;

    Halperin JM, et al. Neurosci Biobehav Rev. 2011;35(3):621-634.

    Activity Levels and ADHD

  • Attention-Deficit/Hyperactivity Disorder

    Pharmacological Treatment

    Stimulants Methylphenidate Dexedrine Amphetamine (compounds)

    Atomoxetine Alpha agonists Guanfacine Clonidine Guan XR or Clon XR + stimulants

    Antidepressants Bupropion Tricyclics

    Modafinil Miscellaneous





  • Pretest Question 1

    Dan is a 9-year-old with ADHD, prominent executive

    dysfunction, some moodiness, and a history of tics. What

    would be the most reasonable initial trial for this patient?

    1. Stimulants

    2. Stimulants plus antipsychotics

    3. Tricyclic antidepressants

    4. Psychotherapy only

  • Representative Studies of Chronic

    Pharmacotherapy in ADHD

    • Study of methylphenidate (MPH) (Abikoff, Hechtman, et al. JAACAP. 2004)

    – Collaboration of Canada and U.S. (initially presented in 1996)

    – Use of immediate-release (IR) MPH

    – Multimodal study of MPH alone (n=50) vs. MPH + multimodal treatment (N=50)

    – Findings at 2 years: excellent response for both groups

    – No additive effect of psychotherapy(ies)

    » Noncomorbid ADHD

    » Comorbid ADHD

    – Relapse with discontinuation

  • Multimodal Treatment Study of Children

    With ADHD (MTA): 8-Year Follow-up

    • All patients improved over time

    • Little difference among initial treatment arms for ADHD outcome at follow-up (initial treatments converge at outcome)

    • MTA children not functioning as well as local normative comparison children (controls; recruited at 2-year follow-up)

    • During 14-month trial, best response at 8 years

    • Initial weight/height declines were followed by rebound of both variables, but ultimate effects uncertain

    • Inconsistent findings on substance abuse

    • Essentially naturalistic examination of sample; frequent cross to other treatments (eg, initial cognitive behavioral therapy (CBT) to medication and vice versa)

    Molina, et al. JAACAP. 2009;48(5):484-500.

  • Protective Effect of Stimulants on Comorbidity

    Biederman, et al. Pediatrics. 2009;124(1):71-78.

    N=140 boys with ADHD at entry; 10-year follow-up data

    N=82 subjects receiving stimulants (mean duration: 6 years) and 30 not on stimulants

    No Stimulant

    No Stimulant