Attention Deficit Hyperactivity DisorderTreatment in Children and Adults

Clinical Aspects of Medication ManagementThomas Weigel, M.D.

Assistant Director of Clinical Measurement, McLean HospitalAssociate Medical Director, Klarman Eating Disorders Center, McLean Hospital

Instructor in Psychiatry, Harvard Medical School

• Add exercise slide under treatment with pic of michael phelps

ADHD Talk Overview

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

History of ADHD• Sir George Still first described

ADHD (1902)• Hyperkinetic Reaction (1920s)• Franklin Ebaugh evidenced that

ADHD could arise from brain injury (1923)

• 1967 Federal government funds (NIMH) first used for studying effect of stimulants on children with hyperactivity

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

• DSM-I: Minimal brain dysfunction (1952)

• DSM-II: Hyperactive reaction of childhood (1968)

• DSM-III: ADD with or without hyperactivity (1980)

• DSM-III-R:Attention-deficit hyperactivity disorder (1987)

• DSM-IV+IV-R: Inattentive type, hyperactive-impulsive type, and combined type (1994)

History of ADHD

DSM-V Revisions to ADHD

• Same criteria as DSM-IV• Onset before age 12 (age 7 in DSM-IV)• 5 symptom criteria in adults (6 in

DSM-IV)• Removed autism-spectrum d/o from

excluders• Elaborated ADHD criteria descriptions

(more examples for adults)

2013 American Psychiatric Association. DSM-5

ADHD Diagnostic Criteria

DSM-V-, APA 2013DSM-V-, APA 2013

Inattention*• Poor attention to details• Careless mistakes• Inattention in tasks or play• Does not seem to listen when spoken to • Does not follow through on:

– Instructions– Work / Schoolwork– Chores

• Disorganized • Avoids tasks that require sustained

mental effort (procrastination)• Loses things• Easily distracted • Forgetful

DSM-V-, APA 2013DSM-V-, APA 2013

*6 inattention or hyperactivity-impulsivity criteria (5 for age 17+)

Hyperactivity-Impulsivity*

• Hyperactivity– Fidgets / Squirms in seat – Leaves seat – Runs about / climbs excessively

(restlessness in adults) – Difficulty playing quietly – “On the go" or "driven by a motor" – Talks excessively

• Impulsivity– Blurts out answers– Difficulty awaiting turn / Impatient– Interrupts or intrudes on others

DSM-V-, APA 2013DSM-V-, APA 2013

*6 inattention or hyperactivity-impulsivity criteria (5 for age 17+)

ADHD-Other Criteria

• Symptoms present before age 12 years• Impairment in 2 settings (school, work, office, home)• The symptoms do not occur exclusively during the course of a

Pervasive Developmental Disorder, Schizophrenia, or other Psychotic Disorder and are not better accounted for by another mental disorder (e.g., Mood Disorder, Anxiety Disorder, Dissociative Disorder, or Personality Disorder)

DSM-V-, APA 2013DSM-V-, APA 2013

ADHD Subtypes• Inattentive Type• Hyperactive-Impulsive Type• Combined Type• Other Specified or Unspecified ADHD

DSM-V-, APA 2013DSM-V-, APA 2013

Case Example• 16 yo girl with

worsening school performance

• Parents wonder what can help—maybe a stimulant?

• No past psych or medical issues

• Meets criteria for inattentive ADHD

• Was overweight -> Started dieting 9 mos ago -> Lost 45# to 79% IBW

• Neuropsych testing shows trouble with executive fxn, concentration, memory

• Do you prescribe a stimulant?

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 Adolescent Psychiatric Clinics of N. America 2000; 9: 541-55.

02468

1012

Children Teens Adults

% A

ffect

ed FemalesMales

Prevalence of ADHD (DSM-IV)

Farone S, Biederman j, Mick E, The age-dependent decline of attention 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.

Youths age 4-17 Ever Diagnosed with ADHD

Youths age 4-17 Receiving Medication Treatment for ADHD

State-based Prevalence Data of ParentReported ADHD Diagnosis and Treatment 

Visser SN, Blumberg SJ, Danielson ML, Bitsko RH, Kogan MD. State-Based and Demographic Variation in Parent-Reported Medication Rates for Attention-Deficit/Hyperactivity Disorder, 2007-2008. Prev Chronic Dis. Jan 2013;10:E09.

Visser S, Danielson M, Bitsko R, et al. Trends in the Parent-Report of Health Care Provider-Diagnosis and Medication Treatment for ADHD disorder: United States, 2003–2011. J Am Acad Child Adolesc Psychiatry. 2013

Epidemiology (Who has it?)• More common in lower socio-

economic population• Gender ratios

– Clinical M:F = 10:1– Non-clincal M:F = 3:1– Adults M:F = 1.5:1– ADHD may be less disruptive in

women– Could be increased environmental

exposure (head injury) in males• May be under-identified and

under-treated in minority groupsBiederman J, Faraone, S. The MGH studies of gender influences on ADHD in youth and relatives. Psychiatric Clinics of N. America 2004; 27: 225-32.

Co-morbidity (other diagnoses)

• 68.2% have a co-morbid condition

NIMH Multimodal Treatment Study of ADHD (MTA): Implications and Applications for Primary Care Providers Jensen, PS. Developmental & Behavioral Pediatrics. 2001 22(1) 60-72Elia et al., 2008 J. Elia, P. Ambrosini and W. Berrettini, ADHD characteristics: I. Concurrent co-morbidity patterns in children & 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 deficit hyperactivity disorder and comorbid disorders: issues of overlapping symptoms, Am. J. Psychiatry 152 (1995), pp. 1793–1799. Curr Opin Neurol. 2011 Apr;24(2):119-25

Etiology (What caused it?)

• ADHD diagnosis does not imply any specific etiology

• No one theory accounts for all cases

• Most likely multi-factorial

Etiology: Biological Risk Factors

• 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.

Etiology: Psychosocial Risk Factors

• Marital or family discord

• Neglect/deprivation• 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: vol 1. The prevalence of psychiatric disorders. British Journal of Psychiatry 1975; 126: 493-509.

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.

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/gatherer needed impulsivity and quickly shifting attention

Genetic attraction to risk-takersOne-room schools, small classes,

individual attention, chores, tight community

Same biological capacity now overwhelmed in demanding society

Case Example• 19 yo female• College student• Trouble with school• Reports all inattentive

ADHD sxs and some impulsivity

• Tried her friend’s Ritalin which “really helped me” study

• No medical issues• No past psych treatment• No family hx of

ADHD/psych/addiction• Would you prescribe a

medicine for ADHD?

Diagnosis of ADHD• History

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

symptoms• Connors Series• Achenbach Child

Behavior Checklist• Teacher Observation of

Classroom Adaptation (TOCA)

• Revised Behavior Problem Checklist (RBPC)-Quay

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)

…butSymptoms

Overlap

Slide graphic courtesy of M. Teicher MD

Diagnosis of ADHD• Tests

– Not necessary or sufficient for a diagnosis– Psychometric and neuropsychological tests for attention,

organization, impulsivity and executive function• Quotient System (Marty Teicher MD)

– 20-minute test– Measures micro-motion (head)– Analyzes impulsivity and shifts in attention– Compares to database of Normal and ADHD Controls

• Continuous Performance Test• Matching Familiar Figures• Reaction time tests• Wisconsin Card Sorting Test• Paired Associate Learning• Porteus Mazes• Stroop Color Word Test• Wechsler Intelligence Scale for Children

Teicher MH, Ito Y, et al. Objective Measures of Hyperactivity and Attentional Problems in ADHD. J Am Acad Child Adolescent Psych, 35(3): 334-342, 1996

Teicher MH, Lowen SB, et al. Novel Strategy for the Analysis of CPT Data Provides New Insight into the Effects of Methylphenidate on Attentional States in Children with ADHD. J Child Adolescent Psychopharmacology 14 (2): 219-232, 2004.

Untreated ADHD ComplicationsProne to accidents:

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

Increased likelihood of:-Depressive disorders-Anxiety disorders-Alcohol and drug abuse

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

rejection Missed 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 in youth with ADHD? A 10-year follow-up study. Pediatrics 2009; 124: 71-78.

Adult ADHD• Age-dependent decline in

symptoms• People develop better

impulse control, better attention spans and more sedate habits (less hyper) as they grow older.

• Rely on history from the patient and significant others

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

Adult ADHD: Marketing and Prescriptions Written (ages 20-39)

• 2007: 5,600,000 • 2012: 16,000,000

Treatment of ADHD• Medications• Behavioral treatments

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

interventions

Attention Deficit Hyperactivity Disorder

Medication TreatmentMedication Treatment

Stimulants methylphenidate; amphetamine compounds;

dextroamphetamine Noradrenergic reuptake inhibitors

atomoxetine

Antihypertensives extended-release guanfacine

extended-release clonidine

Other Bupropion; tricyclics

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

FDAApprovedfor ADHD

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 in 1950s

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

Assessment Points(After the 14 months of assigned treatments ended, families were free to choose from treatments available in their communities)

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, NY

LIJ, NY/MCH, CA

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

MTA Study: Multimodal Treatment Study of 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 effective on an absolute basis

Nearly equally effective and Nearly equally effective and superior to both:superior to both:

Medication managementMedication management+ +

behavioral treatmentbehavioral treatment

Medication management Medication management alonealone

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

NIMH Multimodal Treatment of ADHD

NIMH Multimodal Treatment of ADHD: 8-year follow-up

• Functioning improved overall compared to the beginning of the study• No differences in symptoms/functioning among different assigned

treatment groups as children• ADHD Youths > non-ADHD youths

– Academic problems– Social problems– Conduct problems (including run-ins with police)– Depression– Psychiatric hospitalizations

• Best function at 8 years = responded well to treatment & maintained their gains for 2 years

• 61.5% of medicated kids stopped taking medication– Function on no meds = function of those still medicated– Raises questions about whether medication treatment beyond two years

continues to be needed by all.

Molina BSG, et a. The MTA at 8 years: Prospective follow-up of children treated for combined type ADHD in the multisite study. Journal of the American Academy of Child and Adolescent Psychiatry. Online ahead of print March 2009.

v v Storagevesicle

DA TransporterProtein

Cytoplasmic DA

MPH & AMPH inhibit

AMPH is taken up into cell, causing DA release into synapse

Presynaptic Neuron

Synapse

AMPH

AMPH diffuses intovesicle, causing DA release into cytoplasm

AMPH blocks uptake into vesicle

Stimulant Mechanisms of Action

NEpi and DA Receptors

Wilens, Spencer. Pharmacology of Amphetamines. In: Tarter et al, eds. Handbook of Substance Abuse: Neurobehavioral Pharmacology. New York: 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*– Quillivant XR oral suspension*– Metadate CD, Metadate ER– Methylin*, Methylin ER

• Dexmethylphenidate– Focalin*, Focalin XR*

*if cannot swallow pills

Stimulant Dosing

StimulantDuration(hours)

Child StartDose

Adult StartDose

FDA MaxDose

Max Dosing*

AdderallAdderall XR

4-58 (50/50)

5-10 mg/d 10-20 mg/d 60 mg/d 1.0 mg/kg/d

DexedrineDexSpansules

46

5-10 mg/d 10-20 mg/d 60 mg/d 1.0 mg/kg/d

Vyvanse 13 10 mg/d 30 mg/d 70 mg/d 1.0 mg/kg/d

RitalinRitalin LAConcerta

3-48 (50/50)8 (22/78)

5-10 mg/d 20 mg/d 80 mg/d 2.0 mg/kg/d

FocalinFocalin XR

3-48

2.5-5 mg/d 10 mg/d 20 mg/d 1.0 mg/kg/d

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

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: Stimulant

medication. J Am Acad Child Adolesc Psychiatry. 1999;38:503.

Stimulant Controversies• Sudden Death

– No evidence of increased risk in healthy children– Do not use in pts with known hx of cardiac

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 <age 30

• Development of tics– Decrease dose– Switch to another stimulant– Adjunct agent to treat tics – Try non-stimulant medication

• Growth suppression– 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

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: Saunders Press; 2000:573-604.Castellanos FX. Archives of General Psychiatry. 1999; 56:337-338.

Case Example

• 28 yo male• Past dx of ADHD in 5th

grade—neuropsych testing supported dx (parents refused meds)

• Failed out of college• Struggles to hold down

jobs (3 in last yr)

• 7 Inattentive sxs of ADHD

• Drinks on weekends, sometimes to blackout

• Smokes MJ 5-6 times/week

• Wonders if he should try medicine for ADHD. Thoughts?

Stimulant Controversies: Diversion / Misuse

Stimulants do not alter risk of future substance abuse

– Study design: meta-analysis of 15 studies (N = 2565 patients)

– Findings: Treatment of ADHD with stimulant medication neither protects nor increases the risk of later substance use disorders.

JAMA Psychiatry. 2013;70(7):740-749. 2013.Rabiner, et. al. J Atten Disord. 2009 Sep;13(2):144-53.Sepulveda et. Al. J Pharm Pract 2011 Dec;24(6):551-60.

Misuse in college students prescribed stimulants

60-70% used as prescribed36% used too much19% intentionally used with alcohol or drugs8% intranasal use26% diverted medicine to peers

•11% received an ADHD diagnosis including•1 in 5 high school boys•1 in 11 high school girls

•ADHD diagnosis increased by 42% 2003-2011 (5% annual increase)

•7.8% in 2003•11.0% in 2011

•Medication for ADHD increased by 28% 2007-2011 (7% annual increase)

•4.8% in 2007•6.1% in 2011

Stimulant Controversies:Rising Rates

Trends in the Parent-Report of Health Care Provider-Diagnosis and Medication Treatmentfor ADHD: United States, 2003-2011; Youths age 4-17

Centers for Disease Control and Prevention. Increasing Prevalence of Parent-Reported Attention-Deficit/Hyperactivity Disorder Among Children --- United States, 2003 and 2007. MMWR. 2010;59(44):1439-1443.

Stimulant Controversies:Rising Rates

ADHD DiagnosesBy Age

Stimulant PrescriptionsBy Age

CDC Data Compiled by NY Times April 9, 2013. {phone survey-parent reported that a provider diagnosed child with ADHD}

Trends in Prevalence of Stimulant Use in the U.S. Population Age 18 and Younger, 1987–2008. Am J Psychiatry. 2012;169(2):160-166

Total Stimulant Prescription Trend

Treatment of ADHD atomoxetine (Strattera)

• Approved in 2002 for ADHD treatment

• Noradranergic re-uptake inhibitor

• > 10 controlled trials demonstrating 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. Atomoxetine in adults with ADHD: two randomized placebo-controlled studies. Biological Psychiatry 2003; 53: 112-120.

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 starting dose; 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 atomoxetine treatment for children and adolescents with ADHD: a randomized placebo-controlled study. American Journal of Psychiatry 2002; 159: 1896-901.

Treatment of ADHD atomoxetine (Strattera)

– Possible slight increase in suicidal ideation reported 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) and Clonidine (Kapvay) for ADHD

• FDA approved for children ages 6-17 to treat ADHD • Dosing / Half-Life:

– Intuniv 1-4 mg qam (18 hours)– Kapvay 0.05 mg to 0.4 mg qd-bid (12-16 hours)

• Pharmacology: – alpha-2a adrenergic agonists

• 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, et al. A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics. 2008;121(1):e73-e84. Sallee F, 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. Kollins SH, et al. Clonidine extended-release tablets as add-on therapy to psychostimulants in children and adolescents with ADHD. Pediatrics. 2011; 127(6):1406-1413.

Treatment of ADHDOther Medications*

• buproprion (Wellbutrin)

• Tricyclic antidepressants

*Not FDA approved for treatment of ADHD.*Not FDA approved for treatment of ADHD.

Bupropion (Wellbutrin) in ADHD*

• 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.*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. Americal Journal of Psychiatry 2001; 158: 282-88. Wilens T, Haight BR, Horrigan JP, et al. Bupropion XL in adults with ADHD: 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

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

*Not FDA approved for treatment of ADHD.*Not FDA approved for treatment of ADHD.

Summary: Pharmacotherapy for ADHD

• Stimulants, atomoxetine, extended-release guanfacine, and extended-release clonidine are FDA approved

• Antidepressants (bupropion and TCAs) are second-line agents

• 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/play

• 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.

Treatment of ADHDBehavioral Strategies

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

commands– Establishing house

rules– Time out procedures– Structure time

Connecting Through Play• Tighten the screws with limits

and rules or loosen up with play?

• Children have a need for connectedness, security and attachment

• Play can facilitate these bonds• Connect before you direct or

get angry• "Pretend... that we're really

gonna be late and you're really mad"

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.

Treatment of ADHDExercise

• 20-60 minutes/day of exercise can improve inattention and hyperactivity in ADHD

Medina, J.A., Netto, T.L.B., Muszkat, M. et al. ADHD Atten Def Hyp Disord (2010) 2: 49. doi:10.1007/s12402-009-0018-y

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.

Assistant Director of Clinical Measurement, McLean HospitalAssociate Medical Director, Klarman Eating Disorders Center, McLean Hospital

Instructor in Psychiatry, Harvard Medical School

Stimulant Controversies-CVFDA analysis of amphetamines and methylphenidates from 1992-2005

• 38 cases of sudden death on stimulants (28 in children)

– 12/28 children had structural cardiovascular abnormalities

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

• General population (not on stimulants)

– Sudden death rate in children/adolescents: 4-8 per-million per-year

– Rate in pts treated with amphetamines similar to basal rate

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

abnormalities with sudden death (about 50% have CV structural abnormality)

• Conclusions:– No evidence of increased risk in

healthy children– Sudden death in kids with structural CV

abnormalities on stimulants equated to strenuous exercise

– Do not use in pts with known hx of cardiac 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 <age 30

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