Perspective Truth on ADHD & Medications Thomas L. Matthews, M.D. Associate Dean of Student Affairs Professor of Psychiatry
Disclosures National Institute of Health ADHD and Aggression Study Co- Investigator No other disclosures
Objectives 1. Discuss ethical concerns with the diagnosis of ADHD, and review the makeup of the treatment team. 2. Review the history of ADHD and how the diagnosis has evolved over the years. 3. Explain the importance of early recognition and diagnosis of ADHD, along with benefits of early treatment. 4. Discuss the scientific evidence and clinical observations supporting the efficacy and safety of the various pharmacologic and non-pharmacologic treatments available. 5. Discuss the importance of recognizing co-morbid psychiatric and medical illnesses in the diagnosis of ADHD. 6. Time for Question & Answer session.
WHAT IS ADHD?
ADHD Historical Timeline Minimal Brain Damage Efficacy of Amphetamine Hyperkinetic Reaction of Childhood (DSM-II) Attention Deficit Hyperactivity Disorder (DSM-III-R) 1930 1937 1950 1968 1980 1987 1994 2015 Minimal Brain Dysfunction Hyperactive Child Syndrome Attention Deficit Disorder + or - Hyperactivity (DSM-III) ADHD (DSM-IV) Attention Deficit/Hyperactivity Disorder (DSM-V)
Etiology ADHD is a heterogeneous behavioral disorder with multiple possible etiologies CNS=Central Nervous System
Domains of Impairment Domains of Impairment Interpersonal relationships peer family authority School or occupational functioning Leisure activities Self-esteem
ADHD Core Symptom Areas Inattention Impulsivity/Hyperactivity
ADHD: DSM-V Criteria for Predominantly Inattentive Type Inattention Six or more of the following in kids (5 for adults) seen often: Inattention to details/ makes careless mistakes Difficulty sustaining attention Seems not to listen Fails to finish tasks Difficulty organizing Avoids tasks requiring sustained attention Loses things Easily distracted Forgetful American Psychiatric Association. DSM-IV;1994.
ADHD: DSM-V Criteria for Predominantly Hyperactive-Impulsive Type Impulsivity/Hyperactivity Six or more of the following in kids (5 for adults) seen often: Impulsivity Blurts out answer before question is finished Difficulty awaiting turn Interrupts or intrudes on others Hyperactivity American Psychiatric Association. DSM-IV;1994. Fidgets Unable to stay seated Inappropriate running, climbing (restlessness) Difficulty in engaging in leisure activities quietly On the go Talks excessively
DSM-V Diagnostic Criteria Symptoms of inattention OR impulsivity/hyperactivity: have persisted for 6 months and are more frequent and severe than is typical of the individual s level of development Have multiple symptoms present prior to age 12 cause some impairment in two or more settings cause significant impairment in social, academic, or occupational functioning are not better accounted for by another mental disorder (Hyperactivity is NOT required for a diagnosis) American Psychiatric Association. DSM-IV;1994.
DSM-V Subtypes ADHD Predominantly Inattentive Type criteria met for inattention but not for impulsivity/hyperactivity Inattention ADHD Predominantly Hyperactive- Impulsive Type criteria met for impulsivity/hyperactivity but not for inattention Impulsivity/Hyperactivity ADHD Combined Type criteria are met for both inattention and impulsivity/hyperactivity Inattention Impulsivity/Hyperactivity American Psychiatric Association. DSM-IV;1994.
Course of the Disorder Hyperactivity Impulsivity Inattention Time
DIAGNOSTIC CONCERNS
Who is the Treatment Team? Each person of the treatment team has a unique role. Roles may overlap. Psychiatrists Therapists Pediatrics & Family Medicine Teachers Patients Parents Advocacy Groups
Ethical Concerns Making the diagnosis poses an ethical issue in that a child's behavior may be labeled deviant. Should a diagnosis be given in order to meet eligibility criteria for special services in school if the child needs them. Parents sometimes resist the diagnosis because of the stigma that may adversely affect their child's self-image, or that a psychiatric diagnosis will follow their child from this point on, leading to discrimination.
Ethical Concerns Some parents strongly desire the diagnosis in order to secure special services for their child or to access medication as an aid in controlling the child's behavior. In some instances, the child does not meet the diagnostic criteria, but parents insist that the child must be ADHD because the child's grades are not as good as they expect or the child's behavior is uncontrollable.
How Diagnosis is Made & What is the Purpose Made: Psychiatric Evaluation Psychological Testing Observation Parent Reports School Reports Family History Should be diagnosis of exclusion Purpose: Decrease hyper/ impulsive behaviors Improve attention Decrease Aggression School Accommodations Improve Learning Improve Self-Esteem
Non-Clinical Diagnoses Many things can mimic ADHD Depression, Anxiety, stress, too much sugar, caffeine, etc. Patients and families can get confused with non-clinicians making diagnoses People may not understand exactly what the diagnosis implies, and only medias perception.
TREATMENTS FOR ADHD
3 Typical Parent Responses to Meds (a) parents who come to the office for the primary purpose of obtaining the medication because they believe that the medication is the key to gaining control of their child's behavior (b) parents who are staunchly opposed to medication because they view it as "drugging" their child or encouraging substance abuse (c) parents who may or may not be aware of medication for ADHD and who are open-minded on the subject.
Only about one in three diagnoses of ADHD are not complicated by another mental-health disorder. Children s Mercy Hospital & Clinics
MTA Results All treatments led to improvement in core ADHD symptoms Medication management alone Medication management +behavioral treatment Nearly equal effectiveness and superior to both: Behavioral treatment alone Community-based treatment MTA Cooperative Study Group. Arch Gen Psychiatry 1999;56:1073.
Medications Stimulants: Vyvanse, Adderall XR, Dextrostat, Adderall, ProCentra, Desoxyn Concerta, Daytrana, Focalin XR, Ritalin LA, Ritalin SR, Methylin, Ritalin, Focalin, Non-Stimulants: alpha-agonists, Intuniv, Kapvay, Strattera, Wellbutrin
Stages of Medication RX for ADHD 1. Trial of a single stimulant, try different formulations for duration action 2. Trial of stimulant in alternate class MPH fail AMP fail AMP MPH 3. Trial of Strattera, Intuniv, or Kapvay 4. No response to any the above: consultation
STIMULANTS
Choosing a stimulant On average MPH and AMP have equal efficacy and degree of adverse events Wide individual variation in how patients respond to stimulant class/formulations No clinical predictors of stimulant response exist Careful individual trials are needed
Methylphenidate (MPH) Concerta Focalin Focalin XR Ritalin Ritalin LA Daytrana Metadate Osmotic pump, small dose released in AM, the rest released gradually over the day- 10-12 hour action D-methylphenidate isomer only (l-methylphenidate is inactive, not absorbed into blood stream)- may have slightly longer action than d, l MPH Immediate and delayed release beads, gives 10-12 hour action in laboratory classroom Immediate release d,l MPH, each dose last about 4 hours Immediate and delayed release beads, gives 8 hour action D,l MPH absorbed directly into bloodstream though skin, if patch worn 9 hours, gives 10-12 hour action D, l MPH, 30% released immediately, 70% release later in day, 8 hour action
Amphetamine (AMP) Adderall Adderall XR Dexedrine Dexedrine Spansule Vyvanse 75% d-amp, 25% l-amp (Mixed salts amphetamine)-has about a 6 hour action, but may be 8 hours in some children Immediate and long release beads, gives 10-12 hour duration D-AMP, has 6 hour action Older long release technology, 8-10 hour action After absorption from GI tract, Lisdexamfetamine is converted to dextroamphetamine and l-lysine, gives 10-12 hour duration, perhaps less liklihood of acute abuse
First Line Treatment Starting Dose Max Dose Adderall, Dexedrine, Dextrostat Adderall XR, Dexedrine spansule Vyvanse (12 hours) Total daily dose of MPH-IR Divide bid or tid Concerta (12 hours) Metadate & Ritalin LA (8 hours) Focalin XR (10 hours) <50 lbs 2.5 mg qam 50-65 lbs 65-100 lbs >100 lbs 2.5 mg bid 5.0 mg bid <50 lbs 7.5 mg bid 5 mg 5 mg qam 20 mg qam 10 mg 18 mg qam 10 mg qam 5 mg qam 10 mg qam 30 mg qam 20 mg 18 mg qam 10 mg qam 10 mg qam 15 mg qam 40 mg qam 30mg 36 mg qam 20 mg qam 15 mg qam 50-65 lbs 65-100 lbs Adult size 10 mg bid 12.5 mg bid 15 mg bid 20 mg bid 20 mg qam 50 mg qam 40 mg 54 mg qam 30 mg qam 20 mg qam 25 mg qam 60 mg qam 50 mg 54 mg qam 30 mg qam 25 mg qam 30 mg qam 70 mg qam 60 mg 72 mg qam 40 mg qam 30 mg qam 40 mg qam 80 mg 108mg qam 60 mg qam 40 mg qam
AAP Recommendations for Stimulant Use
Non-Stimulants Strattera
Strattera (atomoxetine) A noradrenergic reuptake inhibitor Non-stimulant treatment has less risk of abuse Dosing: 10, 18, 25, 40, 60mg Once a day or divide BID. Give HS if reports sedation Main side effects: sedation, stomach upset
Weight Range Strattera (child & adol <125 lbs) Starting dose (3-7 days) (0.5mg/kg/day) Target dose (1.2-1.8 mg/kg/day) 40-62 lbs 18 mg qam/pm 18 or 25mg BID 63-93 lbs 25 mg qam/pm 25 mg BID 94-125 lbs 40 mg qam/pm 40 mg BID >125 lbs 40 mg qam/pm 40 mg BID (Max 50 BID)
Strattera (atomoxetine) Specific noradrenergic reuptake inhibitor (cont d) Rare hepatitis reported One case confirmed/3.4 million exposures One case suspected/3.4 million exposures Possible slight increase in suicidal ideation reported in clinical trials 0.37% atomoxetine vs 0.0% placebo One suicide attempt/1,357 cases; no suicides Strattera (atomoxetine HCL) [package insert]. Indianapolis, Ind: Eli Lilly and Co; 2006. Michelson D, et al. Am J Psychiatry. 2002;159:1896-1901.
Non-Stimulants Alpha Agonists
Alpha Agonist Summary Clonidine Increasingly used in single dose in PM for insomnia secondary to stimulants (0.05 to 0.1 mg q HS) Declining role for treatment of daytime ADHD due to efficacy issues as well as sedation Now have long-acting form: Kapvay Guanfacine Both immediate release and Intuniv being used more in ADHD Non responders to stimulants and atomoxetine Patients with stimulant-induced tics whose ADHD responds only to stimulants
Alpha Agonists Preadolescent doses Clonidine Guanfacine Day 1-4 0.05 mg qhs 0.5 mg qhs Day 5-9 0.05 mg qam & HS 0.5 mg qam & HS Day 10-14 0.05 mg tid 1 mg bid Day 14 and up 0.1 mg tid 1 mg tid Adolescent (>100 lbs) Clonidine Guanfacine Day 1-4 0.05 mg qhs 0.5 mg qhs Day 5-9 0.1 mg qhs 1 mg qhs Day 10-14 0.1 mg bid 1 mg bid Day 14 and up 0.1 mg tid/qid 1 mg tid/qid
Intuniv & Kapvay dosing Intuniv Kapvay Week 1 1mg qday 0.1mg qhs Week 2 1mg qday 0.1mg BID Week 3 3mg qday 0.1mg qam & 0.2mg qhs (if needed) Week 4 4mg qday (if needed) 0.2mg BID (if needed)
COMORBIDITIES
Comorbidity Issues Dep/Anx ADHD ODD/CD Learning Disorders
ADHD Childhood Common Comorbid Diagnoses Approximate Prevalence Rate in Children With ADHD (%) Male Female Biederman et al. JAACAP 1996;35:343. Pliszka. J Clin Psychiatry 1998:59(suppl 7):50. Biederman et al. JAACAP 1999;38:966. Spencer et al. Pediatric Clin N Am 1999:46:915.
ADHD Adulthood Common Comorbid Diagnoses Approximate Life-time Prevalence in Adults with ADHD (%) Male Female Biederman et al. Am J Psychiatry 1993;150:1792. Biederman et al. Psychiatry Research 1994;53:13. Shekim et al. Compr Psychiatry 1990;31:416.
ADHD and Comorbid Disorders in Children Bipolar Disorder/Juvenile Mania early symptoms are easily confused with ADHD: distractible, impulsive, hyperactive, disruptive, labile moods differentiated from ADHD: extremely irritable, explosive, affective storms prolonged and aggressive temper outbursts behaviors tend to be chronic rather than episodic >10% of ADHD youth may have comorbid mania Biederman et al. JAACAP 1996:35:997. Spencer et al. Pediatric Clin N Am 1999:46:915.
Difference in Mania Criteria: PEA-BP * and ADHD Patients Patients (%) 100 90 80 70 60 50 40 30 20 10 0 89.3 13.6 P < 0.0001 PEA-BP* (n = 93) ADHD (n = 81) CC (n = 94) 86 71 39.8 9.9 4.9 6.2 0 1.1 0 1.1 Elated Mood Grandiosity Flight and/or Racing Thoughts DSM-IV Mania Criteria Decreased Need for Sleep *PEA-BP = Prepubertal & early adolescent bipolar disease phenotype ADHD = Attention deficit hyperactivity disorder CC = Normal community control group Craney JL, Geller B. Bipolar Disord. 2003;5:243-256.
Poor Judgment Symptoms: PEA-BP and ADHD Patients 100 90 90.3 P < 0.0001 PEA-BP (n = 93) ADHD (n = 81) CC (n = 94) 80 Patients (%) 70 60 50 40 30 20 10 0 44.4 Total Poor Judgment 3.2 43 6.2 65.6 11.1 0 0 0 63.1 65.6 23.5 24.7 Hypersexuality Daredevil Acts Silliness Uninhibited People Seeking Items Used to Rate Poor Judgment Criterion 3.2 Craney JL, Geller B. Bipolar Disord. 2003;5:243-256.
Overlapping Mania Symptoms: PEA-BP and ADHD Patients 120 P < 0.0002 PEA-BP (n = 93) ADHD (n = 81) CC (n = 94) 100 97.9 96.8 93.6 100 96.3 95.1 Patients (%) 80 60 40 71.6 81.5 20 0 11.7 11.7 3.2 2.1 Irritable Mood Accelerated Speech Distractibility Increased Energy DSM-IV Mania Criteria Craney JL, Geller B. Bipolar Disord. 2003;5:243-256.
QUESTIONS?
Thank You!