18
Attention-Deficit Hyperactivity Disorder Thomas Weigel, M.D. 1 Attention Deficit Hyperactivity Disorder Treatment in Children and Adults Clinical Aspects of Medication Management Thomas Weigel, M.D. Director, ADHD Outpatient Clinic, McLean Hospital Associate Medical Director, Klarman Eating Disorders Center, McLean Hospital Instructor in Psychiatry, Harvard Medical School ADHD Talk Overview • History Diagnostic criteria Epidemiology (Who has it?) Etiology (Why do they have it?) Making the diagnosis • Treatment History of ADHD Hyperkinetic reaction (1920s) Minimal brain damage Minimal brain dysfunction Psycho-neurologic integration deficit Hyperactive reaction of childhood (1968) Hyperactive child syndrome Dole R. The history of adult attention-deficit disorder. Psychiatric Clinics of N. America 2004; 27: 203-14.

Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

  • Upload
    others

  • View
    2

  • Download
    0

Embed Size (px)

Citation preview

Page 1: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 1

Attention Deficit Hyperactivity DisorderTreatment in Children and Adults

Clinical Aspects of Medication Management

Thomas Weigel, M.D.Director, ADHD Outpatient Clinic, McLean Hospital

Associate Medical Director, Klarman Eating Disorders Center, McLean HospitalInstructor in Psychiatry, Harvard Medical School

ADHD Talk Overview

• History• Diagnostic criteria• Epidemiology (Who has it?)• Etiology (Why do they have it?)• Making the diagnosis• Treatment

History of ADHD

• Hyperkinetic reaction(1920s)

• Minimal brain damage• Minimal brain dysfunction• Psycho-neurologic

integration deficit• Hyperactive reaction of

childhood (1968)• Hyperactive child

syndrome

Dole R. The history of adult attention-deficit disorder. Psychiatric Clinics of N. America 2004; 27:203-14.

Page 2: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 2

History of ADHD

• Attention-deficit disorder(1980)

• Attention-deficit disorder,residual type

• Attention-deficithyperactivity disorder(1987)

• Inattentive type,hyperactive-impulsivetype, and combined type(1994)

ADHD Diagnostic Criteria

Six (or more) of thefollowing criteria aremet for eitherinattention orhyperactivity-impulsivity

DSM-IV-TR, APA 2000

Inattention• often fails to give close attention to details or makes careless mistakes

in schoolwork, work, or other activities• often has difficulty sustaining attention in tasks or play activities• often does not seem to listen when spoken to directly• often does not follow through on instructions and fails to finish

schoolwork, chores, or duties in the workplace (not due to oppositionalbehavior or failure to understand instructions)

• often has difficulty organizing tasks and activities• often avoids, dislikes, or is reluctant to engage in tasks that require

sustained mental effort (such as schoolwork or homework)--AKAProcrastination

• often loses things necessary for tasks or activities (e.g., toys, schoolassignments, pencils, books, or tools)

• is often easily distracted by extraneous stimuli• is often forgetful in daily activities

DSM-IV-TR, APA 2000

Page 3: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 3

Hyperactivity-Impulsivity

• Hyperactivity– often fidgets with hands or feet or squirms in seat– often leaves seat in classroom or in other situations in which remaining

seated is expected– often runs about or climbs excessively in situations in which it is

inappropriate (in adolescents or adults, may be limited to subjectivefeelings of restlessness)

– often has difficulty playing or engaging in leisure activities quietly– is often "on the go" or often acts as if "driven by a motor"– often talks excessively

DSM-IV-TR, APA 2000

Hyperactivity-Impulsivity

• Impulsivity– often blurts out answers before questions

have been completed– often has difficulty awaiting turn– often interrupts or intrudes on others (e.g.,

butts into conversations or games)

DSM-IV-TR, APA 2000

ADHD-Other Criteria

• Some hyperactive-impulsive or inattentive symptoms that causedimpairment were present before age 7 years

• Some impairment from the symptoms is present in two or moresettings (e.g., at school [or work] and at home).

• There must be clear evidence of clinically significant impairment insocial, academic, or occupational functioning

• The symptoms do not occur exclusively during the course of aPervasive Developmental Disorder, Schizophrenia, or other PsychoticDisorder and are not better accounted for by another mental disorder(e.g., Mood Disorder, Anxiety Disorder, Dissociative Disorder, orPersonality Disorder)

DSM-IV-TR, APA 2000

Page 4: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 4

ADHD Subtypes

• Predominantly inattentive type• Predominantly hyperactive-impulsive type• Combined type• ADHD-not otherwise specified

DSM-IV-TR, APA 2000

Epidemiology (who has it?)• 8-12% of school children worldwide• Lower prevalence noted in some studies in

other countries is criteria dependent (ICD-10 < DSM-IV)

Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child AdolescentPsychiatric Clinics of N. America 2000; 9: 541-55.

02468

1012

Children Teens Adults

% A

ffect

ed FemalesMales

Prevalence of ADHD

Farone S, Biederman j, Mick E, The age-dependent decline of attentino deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychological Medicine, 2006, 36: 159-165. 2000;105:1158-1170.

US Department of Health and Human Services. Report of the Surgeon General, 1999.

Page 5: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 5

Epidemiology (Who has it?)• More common in:

– Men• Difference: Clinical > Non-clincal

(females less likely to be referred fortreatment)

• ADHD may be less disruptive inwomen

• Could be increased environmentalexposure (head injury) in males

– Lower economic strata– Under-identified and under-treated

in minority groups

Biederman J, Faraone, S. The MGH studies of gender influences on ADHD in youth and relatives. Psychiatric Clinicsof N. America 2004; 27: 225-32.

Co-morbidity (other diagnoses)

• 40% have oppositional defiantdisorder

• 25% have an anxiety disorder• 20-30% have a mood disorder• 20-25% have a learning disorder• 2% have Tourette’s disorder

– 50% of patients with Tourette’s haveADHD

Elia et al., 2008 J. Elia, P. Ambrosini and W. Berrettini, ADHD characteristics: I. Concurrent co-morbidity patterns inchildren & adolescents, Child Adolesc. Psychiatry Ment. Health 2 (2008), pp. 15–23.Milberger et al., 1995 S. Milberger, J. Biederman, S.V. Faraone, J. Murphy and M.T. Tsuang, Attention deficithyperactivity disorder and comorbid disorders: issues of overlapping symptoms, Am. J. Psychiatry 152 (1995), pp.1793–1799.

Risk Factors for ADHDBiological

• Brain injuries• Low birth weight• Fetal alcohol exposure• Maternal smoking in

pregnancy• Lead exposure

Biederman J, Faraone S, Attention-deficit hyperactivity disorder, Lancet 2005; 366: 237-48.

Page 6: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 6

Risk Factors for ADHDPsychosocial

• Marital or family discord• Neglect/deprivation• Reduced family cohesion• Low socioeconomic status• Large family size• Parental psychopathology• Foster placement

Rutter M, Cox A, Tupling C, Berger M, Yule W. Attainment and adjustment in two geographical areas: vol1. The prevalence of psychiatric disorders. British Journal of Psychiatry 1975; 126: 493-509.

Etiology (What caused it?)

• ADHD diagnosis doesnot imply any specificetiology

• No one theoryaccounts for all cases

• Most likely multi-factorial

Etiology (What caused it?)• Localized brain dysfunction

– Frontal-subcortical circuits• Executive function: inhibition, working memory, set-shifting,

interference control, planning, sustained attention• Reduced volume size in these regions on structural imaging• Less activation in these areas on functional imaging

– Striatum (subcortical structure)• Many dopamine synapses• Vulnerable to perinatal hypoxia• Related to hyperactivity and impulsivity if not intact

Biederman J, Faraone S, Attention-deficit hyperactivity disorder,Lancet 2005; 366: 237-48.

Page 7: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 7

Etiology (What caused it?)• Genetic factors

– Heritability: 75%– 4-5x greater probability if full sibling

has ADHD– Genes with small effect:

• Dopamine D4 + D5 receptor• Dopamine transporter SLC6A3

• Serotonin transporter SLC6A4

• Serotonin receptor HTR1B• Synaptic-vesicle transporter SNAP25

– Genes with large effect:• None

Biederman J, Faraone S, Attention-deficit hyperactivity disorder, Lancet 2005; 366: 237-48.

Etiology (What caused it?) Evolution in a complex society

Prehistoric hunter/gathererneeded impulsivity andquickly shifting attention

One-room schools, smallclasses, individualattention, chores, tightcommunity

Same biological capacitynow overwhelmed indemanding society

Diagnosis of ADHD

• History– Patient– Family– School/teachers– Standardize and quantify

symptoms• Connors Series• Achenbach Child

Behavior Checklist• Teacher Observation of

Classroom Adaptation(TOCA)

• Quay Problem Checklist

Page 8: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 8

Diagnosis of ADHD

• Rule out other diagnoses– Conduct and oppositional defiant disorders– Mood disorders (depression, bipolar disorder)– Anxiety disorders (panic, OCD, generalized)– Post-traumatic stress disorder– Learning and developmental disorders– Psychosis– Parenting problems (limits, structure, consistency)– Medications (asthma, anti-seizure, other)

Diagnosis of ADHD• Tests

– Not necessary or sufficientfor a diagnosis

– Psychometric andneuropsychological tests

• Quotient Test• Continuous Performance

Test• Matching Familiar Figures• Reaction time tests• Wisconsin Card Sorting

Test (older patients)• Paired Associate Learning• Porteus Mazes• Stroop Color Word Test• Wechsler Intelligence

Scale for Children

Teicher MH, Ito Y, Glod CA, Barber NI. Objective measurement of hyperactivity and attentional problems inADHD. J Am Acad Child Adolesc Psychiatry. 1996;35(3):334-342.

Adult ADHD• Age-dependent decline in

symptoms• People develop better

impulse control, betterattention spans and moresedate habits as they growolder.

• Rely on history from thepatient, significant other andoccasionally an employer

Faraone S, Biederman J, Mick E. The age-dependent decline of ADHD: a meta-analysis of follow-upstudies. Psychological Medicine, 2006, 36: 159-65.

Page 9: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 9

Untreated ADHD ComplicationsProne to accidents:

-50% bike accidents-33% ER visits-2-4x more MVA’s

Increased likelihood of:Depressive disordersAnxiety disordersAlcohol and drug abuse

Poor team performanceAcademic failure and grade retentionSocial ineptness, unpopularity, and peer

rejectionMissed development of life-long good

work habits and attitude

DiScala C, Lescohier I, Barthel M, Li G. Injuries to children with ADHD. Pediatrics 1998; 102: 1415-21.Biederman J, Monuteaux M, Spencer T, Wilens T, Faraone S. Do stimulants protect against psychiatric disorders inyouth with ADHD? A 10-year follow-up study. Pediatrics 2009; 124: 71-78.

Treatment of ADHD

• Medications• Behavioral treatments

– Cognitive behavioral skill training– Parent training– Teacher consultation and school-based

interventions

Attention DeficitHyperactivity Disorder

Medication Treatment

Stimulants Methylphenidate; amphetamine compounds;

dextroamphetamine

Noradrenergic reuptake inhibitorsAtomoxetine

Antihypertensives extended-releas guanfacine clinidine (not approved)

Antidepressants Bupropion; tricyclics; venlafaxine

Other Mood stabilizers and Neuroleptics

(Updated 2009) Biederman J, Faraone S, Attention-deficit hyperactivity disorder, Lancet 2005; 366: 237-48.

FDAApprovedfor ADHD

Page 10: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 10

Treatment of ADHDMedications: Stimulants

• Stimulants– Best documented efficacy in

controlled trials– Most specific for ADHD

symptoms– Linear benefit with dosage until

side effects– Fast acting and safe (although

Schedule II)– Dexedrine (dextroamphetamine)

developed in 1920s and Ritalin(methylphenidate) developed in1950s

Prince J., Child Adolesc Psychiatr Clin N Amer, 2006 January 15(1) 13-50

Assessment Points

Baseline EarlyTreatment

(3 m)

Mid-Treatment

(9 m)

End ofTreatment

(14 m)

FirstFollow-up

(24 m)

SecondFollow-up

(36 m)

14-m Treatment

Phase

10-m Follow-up

Phase

22-m Follow-up

Phase

0 362414Month

RecruitmentScreeningDiagnosis

RANDOM

ASSIGNMENT

579 Subjects7 to 9 yrs old

ADHD-Combined

Medication Only144 Subjects

Behavioral Only144 Subjects

Combined Treatment145 Subjects

Community Treatment146 Subjects

Pre-Baseline

6 sites in N Amer:UC Irvine, CA

U Pittsburg, PADuke U, NC

UC Berkeley, CAColumbia U, NYLIJ, NY/MCH, CA

MTA Cooperative Group. Arch Gen Psychiatry. 1999;56(12):1073-1086.

MTA Study: Multimodal Treatment Studyof Children with ADHD

NIMH and US Department of Education

Behavioral treatment alone Community-based treatment

Follow-up at 14 and 24 months found all treatment arms to be effectiveon an absolute basis

Nearly equally effective andsuperior to both:

Medication management+

behavioral treatment

Medication managementalone

MTA Cooperative Group. Arch Gen Psychiatry. 1999;56(12):1073-1086.MTA Cooperative Group. Pediatrics.2004;113(4):754-761.

NIMH Multimodal Treatmentof ADHD

Page 11: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 11

v v Storagevesicle

DA TransporterProtein

Cytoplasmic DA

MPH & AMPHinhibit

AMPH is taken upinto cell, causing DArelease into synapse

Presynaptic Neuron

Synapse

AMPH

AMPH diffuses intovesicle, causing DA release into cytoplasm

AMPH blocks uptake into vesicle

Stimulant Mechanisms ofAction

NEpi and DA Receptors

Wilens, Spencer. Pharmacology ofAmphetamines. In: Tarter et al, eds.Handbook of Substance Abuse:Neurobehavioral Pharmacology. NewYork: Plenum Press; 1998:501.Slide Courtesy of Jeff Prince, MD

AMPH – amphetamineDA - dopamineMPH – methylphenidateNEpi - norepinephrine

Treatment of ADHDMedications: Stimulants

• Stimulants– Amphetamines

• Mixed-amphetamine salts– Adderall– Adderall XR

• Dextroamphetamine– Dexedrine– Dexedrine Spansules

• Lisdexamfetamine– Vyvanse

– Methylphenidates• Mixed-methylphenidate salts

– Ritalin, Ritalin LA, Ritalin SR– Concerta, Daytrana patch– Metadate CD, Metadate ER– Methylin, Methylin ER

• Dexmethylphenidate– Focalin, Focalin XR

Stimulant Dosing

3-48

3-48

13

46

4-58

Duration(hours)

2.0 mg/kg/d80 mg/d20 mg/d5-10 mg/dRitalin

Ritalin LA

1.0 mg/kg/d20 mg/d10 mg/d2.5-5 mg/dFocalin

Focalin XR

1.0 mg/kg/d70 mg/d30 mg/d10 mg/dVyvanse

1.0 mg/kg/d60 mg/d10-20 mg/d5-10 mg/dDexedrine

DexSpansules

1.0 mg/kg/d60 mg/d10-20 mg/d5-10 mg/dAdderall

Adderall XR

MaxDosing*

FDA MaxDose

Adult StartDose

Child StartDose

Stimulant

Wilens, et al. Annu Rev Med. 2002;53:113-131Prince J., Child Adolesc Psychiatr Clin N Amer, 2006 January 15(1) 13-50

*Maximum dosing may exceed FDA approved dose limits

Page 12: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 12

Stimulant Dosing Instructions• PATIENT NAME:• DATE:• MEDICATION NAME:• TABLET STRENGTH:• INSTRUCTIONS• Take ____________ each morning for five (5) days. After five (5) days, if there is

no benefit and no side effects,• Then increase the dose to ____________ each morning for five (5) days. After five

(5) days, if there is no benefit and no side effects,• Then increase the dose to ____________ each morning for five (5) days. After five

(5) days, if there is no benefit and no side effects,• Then increase the dose ____________ each morning until we meet again.• Do not exceed a dose of ____________ each morning.• If you have side effects at a particular dose, then reduce the dose by one tablet

each morning and stay on that dose until we meet again, or stop the medication.• Return to see Dr. Tom Weigel in three weeks for a 1/2-hour appointment to discuss

how things are going with the medication.

Treatment of ADHDStimulants

• Side effects– Appetite loss– Sleep disturbance– Restlessness/anxiety– Cramps– Rebound/Crash

• Irritability• Depression

– Tics– Growth slowing

Greenhill L, Halperin JM, Abikoff H: Stimulantmedication. J Am Acad Child AdolescPsychiatry. 1999;38:503.

Stimulant Controversies• Growth suppression in

children receiving consistentmedication– 2 cm in 2 years in MTA study (20%

reduction)– No further reduction if treated 1

additional year– Catch-up or rebound growth may be

possible– Growth Chart with ht/wt q3-4

months if concern

• Development of tics– Tics/Tourettes remain listed as

contraindication to use ofstimulants However,…

– Tics are usually transient; onlyvery rarely do patients developa chronic tic disorder

– When tics occur or increase:• Decrease dose• Switch to another stimulant• Adjunct agent to treat tics• Try non-stimulant medication

Spencer T, et al. Pediatrics. 1998;102:501-506.MTA Cooperative Group. Pediatrics. 2004;113:762-769.Wilens T, Spencer T. In: Child and Adolescent Psychiatric Clinics of North America. Philadelphia, Pa: SaundersPress; 2000:573-604.Castellanos FX. Archives of General Psychiatry. 1999; 56:337-338.

Page 13: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 13

Stimulant Controversies:Diversion / Misuse

• Study design: meta-analysis of 7 studies(N = 1195)

• Stimulant exposure at 10 and 11 years old• Follow-up 4 to 15 years later• Findings:

– Treatment of ADHD significantlydecreases the risk for subsequent substanceabuse (protective odds ratio = 2.0)

– Twice the risk for substance abuse withuntreated ADHD

Wilens, et al. Pediatrics. 2003;11:179-183.Faraone, Wilens. J Clin Psychiatry. 2003;64(suppl 11):S9-S13.

Stimulant Controversies-CVFDA analysis of amphetamines andmethylphenidates from 1992-2005

• 38 cases of sudden death onstimulants (28 in children)

– 12/28 children has structuralcardiovascular abnormalities

– 30 million prescriptions 1999-2003 (7million pts)

• General population (not onstimulants)

– Sudden death rate inchildren/adolescents: 4-8 per-millionper-year

– Rate in pts treated with amphetaminessimilar to basal rate

– Higher rate of sudden death in athletes– Similar ratio for structural CV

abnormalities with sudden death (about50% have CV structural abnormality)

• Conclusions:– No evidence of increased risk in healthy

children– Sudden death in kids with structural CV

abnormalities on stimulants equated tostrenuous exercise

– Do not use in pts with known hx ofcardiac structural/rhythm abnormalities

• Guidelines:– Physical exam– Personal hx of structural heart or

rhythm abnormalities, syncope,dizziness, plapitations, or chest pain

– Family hx of sudden cardiac death <age30

Vitiello B, Understanding the risk of using medications for ADHDwith respect to physical growth and cardiovascular function, Childand Adoles Psychiatric Clinics of N America 2008. 17: 459-74.

Treatment of ADHD atomoxetine (Strattera)

• Approved in 2002 forADHD treatment

• Noradranergic re-uptakeinhibitor

• > 10 controlled trialsdemonstrating efficacy

• Long term studies:continued effectiveness

• Once-daily dosing• Benefit in 1-4 weeks• No on/off effect• May help with anxiety• No abuse potential

Michelson D, Adler L, Spencer T, et al. Atomoxetinein adults with ADHD: two randomized placebo-controlled studies. Biological Psychiatry 2003; 53:112-120.

Page 14: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 14

Treatment of ADHD atomoxetine (Strattera)

• Dosing (4-6+ weeks)– Adult: 40 mg/d x3 days

then 80 mg/d (max 100/d)– Kids: 0.5 mg/kg/d x3 days,

then 1.2 mg/kg/d startingdose; 1.4 mg/kg/d max

• Side effects– Abdominal pain– Insomnia– Decreased appetite– Constipation– Fatigue– Dizziness– Sexual side effects– Depression

Michelson D, Allen AJ, Busner J, et al. Once-daily atomoxetinetreatment for children and adolescents with ADHD: a randomizedplacebo-controlled study. American Journal of Psychiatry 2002; 159:1896-901.

Treatment of ADHD atomoxetine (Strattera)

– Possible slight increase in suicidal ideationreported in clinical trials

• 0.37% Atomoxetine vs. 0.0% placebo• One suicide attempt/1357 cases; no suicides

– Rare hepatitis reported• One case confirmed/3.4 million exposures• One case suspected/3.4 million exposures

Extended-Release Guanfacine(Intuniv)* for ADHD

• FDA approved for children ages 6-17 to treat ADHD (*will be released inNovember)

• Dosing: 1-4 mg qam• Pharmacology:

– half-life = 18 hours– alpha-2a adrenergic agonist

• Efficacy:– improvement in hyperactivity/impulsivity as well as inattention– may be less effective with inattentive-subtype

• Side effects:– somnolence, sedation, abdominal pain, dizziness, hypotension, dry mouth and

constipation– use with caution in patients at risk for bradycardia, hypotension, heart block or syncope

Biederman J, Melmed RD, Patel A, et al. A randomized, double-blind, placebo-controlled study of guanfacine extendedrelease in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics. 2008;121(1):e73-e84.Sallee F, McGough J, Wigal T, et al. Guanfacine extended release in children and adolescents with ADHD: A placebo-controlled trial. J Am Acad Child and Adolesc Psychiatry. 2009; 48(2): 1-11.

Page 15: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 15

Treatment of ADHDOther Medications*

• buproprion(Wellbutrin)

• clonidine (Catapres)• Tricyclic

antidepressants• Mood stabilizers• Neuroleptics/anti-

psychotics

*Not FDA approved for treatment of ADHD.

Bupropion (Wellbutrin) inADHD*

• Dopamine/norepinephrine reuptake inhibitor• Stimulant-like structure• No cardiac conduction delays• Superior to placebo in children

– N= 3 controlled studies (104 subjects)

• Improvement in attention and behavior• Dosing to 6 mg/kg/d (approximately 300-450 mg/d)• Delayed onset of therapeutic action

– 1 to 6 weeks*Not FDA approved for treatment of ADHD.

Wilens T, Spencer TJ, Biederman J, et al. A controlled clinical trial of bupropion for ADHD in adults. AmericalJournal of Psychiatry 2001; 158: 282-88. Wilens T, Haight BR, Horrigan JP, et al. Bupropion XL in adults withADHD: a randomized, placebo controlled study. Biological Psychiatry 2005; 57: 793-801.

Tricyclic Antidepressants*

• Advantages– Long duration of action– Potential benefits on mood

and anxiety– Positive effects on sleep

• Disadvantages– Efficacy < Stimulants– Serious potential cardiac

effects in children– Need for cardiac

monitoring

Biederman J. J Clin Psychiatry. 1998;59(suppl 7):S4-S16.

*Not FDA approved for treatment of ADHD.

Page 16: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 16

Clonidine (Catapres) for ADHD*• Pharmacology: Alpha-2a-noradrenergic agonist• Dosing: 0.05 mg to 0.2 mg up to TID• Also transdermal (patch) dosing• Efficacy

– helpful for hyperactivity and impulsivity– not helpful with attention deficit– 3 controlled trials – efficacy for ADHD– Multiple open trials – efficacy in aggression, impulsivity, ADHD-

related sleep disorders• Side effects: sedation, headaches, depression, rebound

hypertension; controversy of use with stimulants (4 deaths in1990’s but no causal link)

Hunt RD, et al. J Am Acad Child Adolesc Psychiatry. 1985;24:617-619. Hunt RD, et al. Psychopharmacol Bull.1986;22:229-236. Prince JB, et al. J Am Acad Child Adolesc Psychiatry. 1996;35:599-605. Wilens TE,Spencer TJ. J Am Acad Child Adolesc Psychiatry. 1999;38:614-616. Hazell PL, Stuart JE. J Am Acad ChildAdolesc Psychiatry. 2003;42:886-894.

*Not FDA approved for treatment of ADHD.

Summary:Pharmacotherapy for ADHD

• Stimulants, atomoxetine and extended-releaseguanfacine are FDA approved first-line agents

• Antidepressants (bupropion and TCAs) are second-lineagents

• Clonidine is an alternative agent typically usedadjunctively with other medications

• Combined pharmacotherapy for incomplete response:– Stimulant plus atomoxetine, bupropion, tricyclics,

clonidine, or guanfacine

Treating Refractory ADHD

• Evaluate for co-morbidity• Referral for

– Behavioral therapy– Coaching/study skills– Family therapy/parental coaching

• Higher doses of medication(s)• Other Medicines not approved by FDA

Wilens T, Spencer T. Child Adolesc Psychiatr Clin N Am. 2000;9(3):573-603.Wilens T, Dodson W. J Clin Psychiatry. 2004;65:1301-1313.

Page 17: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 17

Treatment of ADHDBehavioral Strategies

• Parent training– Track behavior– Reward system– Catch good behavior– Issuing clear

commands– Establishing house

rules– Time out procedures– Structure time

Treatment of ADHDBehavioral Strategies

• Teacher/School– Build teacher/student bond– Extra structure, consistency

and organization– Decrease distractions– Extra time for tests– Reminders– Rules / Target behaviors– Effective commands– Rewards/punishments– Tutoring– Daily report card

Power T, Tresco K, Cassano M. School-based interventions for students with ADHD.Current Psychiatry Reports. 2009; 11: 407-14.

ADHD and DSM-V work group identified research questions

relating to three broad areas:

1. Diagnostic coverage and exclusions2. Adjusting criteria for key patient characteristics, especially age3. Accounting for severity, heterogeneity, and subtypes--a more “dimensional approach” to

substitute the rigid “categorical approach”

Swanson JM, Wigal T, Lakes K. DSM-V and the future diagnosis of ADHD. Curr PsychiatryRep. 2009 Oct;11(5):399-406

Page 18: Attention-Deficit Hyperactivity Disorder€¦ · other countries is criteria dependent (ICD-10 < DSM-IV) Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child

Attention-Deficit Hyperactivity Disorder

Thomas Weigel, M.D. 18

ADHD and DSM-V Possible Changes

Eliminate ADHD subtypesCreate ADD diagnosisAdd 4 more impulsivity criteriaIncrease age of onset to before age 12 (rather than 7)Lower threshold for ADHD combined dx in adultsRemove autism-spectrum d/o and PDD from excludersElaborate ADHD criteria descriptions (more examples)

2010 American Psychiatric Association. DSM-5: Options Being Considered for ADHD

ADHD Talk Overview

• History• Diagnostic criteria• Epidemiology (Who

has it?)• Etiology (Why do they

have it?)• Making the diagnosis• Treatments

Attention Deficit Hyperactivity DisorderTreatment in Children and Adults

Clinical Aspects of Medication ManagementThomas Weigel, M.D.

Director, ADHD Outpatient Clinic, McLean HospitalAssociate Medical Director, Klarman Eating Disorders Center, McLean Hospital

Instructor in Psychiatry, Harvard Medical School