ADHD: Assessment and Treatment across the Lifespan*

11

ADHD: Assessment and ADHD: Assessment and Treatment across the Treatment across the

Lifespan*Lifespan*Shashank V. Joshi, MD, FAAPShashank V. Joshi, MD, FAAP

Stanford University School of Stanford University School of MedicineMedicine

Jessica R. Oesterheld, MDJessica R. Oesterheld, MD

Tufts University School of MedicineTufts University School of Medicine

22

Question 1Question 1

Which of the listed disorders is the most Which of the listed disorders is the most common co-morbidity with ADHD in common co-morbidity with ADHD in children?children?A-Learning disorders in MathA-Learning disorders in MathB-Learning disorders in expressive languageB-Learning disorders in expressive languageC-Oppositional defiant disorderC-Oppositional defiant disorderD-Separation anxiety disorderD-Separation anxiety disorderE-Gender Identity Disorder of ChildhoodE-Gender Identity Disorder of Childhood

33

Question 2Question 2Which of the following adverse events Which of the following adverse events

have been reported with atomoxetine in have been reported with atomoxetine in adults?adults?A-Sexual side effectsA-Sexual side effectsB-Stevens-Johnson syndromeB-Stevens-Johnson syndromeC-BradycardiaC-BradycardiaD-HypotensionD-HypotensionE-None of the aboveE-None of the above

44


A diagnosis of ADHD in adults must A diagnosis of ADHD in adults must include?include?A-Retrospective history of ADHD symptoms A-Retrospective history of ADHD symptoms

before the age of 12 yearsbefore the age of 12 yearsB- History of school failureB- History of school failureC- History of motor vehicle accidentsC- History of motor vehicle accidentsD- History of failed multiple marriagesD- History of failed multiple marriagesE- History of substance abuseE- History of substance abuse

55


Which of the following statements about Which of the following statements about bupropion is true?bupropion is true? A-It should not be used in youth with a history of A-It should not be used in youth with a history of

seizure disorder seizure disorder B-It should not be used in youth with a history of B-It should not be used in youth with a history of

eating disordereating disorder C-It can be associated with serum sicknessC-It can be associated with serum sickness D-it has off-label use for ADHDD-it has off-label use for ADHD E-All of the aboveE-All of the above

66


Which 2 of the following instruments are Which 2 of the following instruments are useful in diagnosing adult ADHD?useful in diagnosing adult ADHD?A-CAARSA-CAARSB-CARSB-CARSC-BAARSC-BAARSD-WRAADSD-WRAADSE-CARBSE-CARBS

77

Preview*Preview*

History of ADHDHistory of ADHDSubtypes of ADHD and co-morbiditiesSubtypes of ADHD and co-morbiditiesNE and DA pathways NE and DA pathways MTA studyMTA studyMedication Treatments for pediatric ADHDMedication Treatments for pediatric ADHDAdult ADHDAdult ADHD

88

Teaching Points*Teaching Points*

ADHD is a ADHD is a clinicalclinical diagnosis in both youth diagnosis in both youth and adultsand adults

There are several subtypes that have There are several subtypes that have different presentationsdifferent presentations

The drugs of choice are psychostimulants The drugs of choice are psychostimulants and atomoxetine, but there are several and atomoxetine, but there are several other medications that can be effectiveother medications that can be effective

99

ADHD*:ADHD*:

Clinical characteristics:Clinical characteristics:some combination of some combination of severe inattention, severe inattention,

hyperactivity, and impulsivity that begins in hyperactivity, and impulsivity that begins in childhood, and often persists into adult yrs.childhood, and often persists into adult yrs.

Must cause functional impairment across Must cause functional impairment across settings, and must be developmentally settings, and must be developmentally relevantrelevant

some symptoms should be present before age some symptoms should be present before age 77

1010

Attention-Deficit Hyperactivity Attention-Deficit Hyperactivity Disorder (ADHD)Disorder (ADHD)

minimum brain dysfunction, hyperkinetic syndrome of minimum brain dysfunction, hyperkinetic syndrome of childhood (1960s)childhood (1960s)

1980 DSM III: ADD(H)1980 DSM III: ADD(H) 1987 DSM IIIR: ADHD1987 DSM IIIR: ADHD 1994 DSM IV: Subtypes1994 DSM IV: Subtypes

must meet 6 of 9 criteria in a particular category must meet 6 of 9 criteria in a particular category Inattentive type (IA)Inattentive type (IA) Hyperactive-Impulsive type (HI)Hyperactive-Impulsive type (HI) Combined type (CT)Combined type (CT)

1111

ADHD in Childhood:ADHD in Childhood:

EpidemiologyEpidemiology3-7% of school-age children3-7% of school-age childrenboys 4-9x > girlsboys 4-9x > girls

1212

ADHD-Inattentive typeADHD-Inattentive type

Failure to pay close attention to details / Failure to pay close attention to details / frequent careless mistakesfrequent careless mistakes

Difficulty sustaining attention in tasks or playDifficulty sustaining attention in tasks or playNot listening when spoken toNot listening when spoken toNot following through on instructions, and Not following through on instructions, and

failure to finish tasks (schoolwork, chores). failure to finish tasks (schoolwork, chores). Not due to oppositionality or failure to Not due to oppositionality or failure to understandunderstand

1313

ADHD-Inattentive typeADHD-Inattentive type

Difficulty organizing tasks and activitiesDifficulty organizing tasks and activitiesAvoidance of tasks that require sustained Avoidance of tasks that require sustained

mental effortmental effortLosing things necessary for tasks (toys, Losing things necessary for tasks (toys,

assignments, books)assignments, books)Easily distracted by external stimuliEasily distracted by external stimuliOften forgetful in daily activitiesOften forgetful in daily activities

1414

ADHD- Hyperactive/Impulsive ADHD- Hyperactive/Impulsive typetype

Fidgets with hands/ feet, or squirms in seatFidgets with hands/ feet, or squirms in seatLeaves seat in classroom or other situations Leaves seat in classroom or other situations

where sitting is expectedwhere sitting is expectedRuns or climbs excessively in inappropriate Runs or climbs excessively in inappropriate

situationssituationsDifficulty playing or engaging in leisure Difficulty playing or engaging in leisure

activities quietlyactivities quietlyOften “on the go” / “driven by a motor”Often “on the go” / “driven by a motor”Talks excessivelyTalks excessively

1515

ADHD- Hyperactive/Impulsive ADHD- Hyperactive/Impulsive typetype

ImpulsivityImpulsivityBlurts out answers before questions have Blurts out answers before questions have

been completedbeen completedDifficulty waiting turnDifficulty waiting turnInterrupts or intrudes on others Interrupts or intrudes on others

(conversations, games)(conversations, games)

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Other criteriaOther criteria

Some impairing symptoms were present Some impairing symptoms were present before age 7before age 7

Some impairment Some impairment across settingsacross settings (home, school)(home, school)

Clinically significantClinically significant impairment in impairment in social, academic or work functioningsocial, academic or work functioning

Other conditions must be considered as Other conditions must be considered as source of symptomssource of symptoms

1717

ADHD*ADHD*

Co-existing conditions must also be evaluated forCo-existing conditions must also be evaluated for 30-50% of ADHD may be co-morbid with other dx30-50% of ADHD may be co-morbid with other dx

Oppositional Defiant Disorder (ODD)- Pervasive pattern of Oppositional Defiant Disorder (ODD)- Pervasive pattern of negativistic, defiant, disobedient, and hostile behaviors toward negativistic, defiant, disobedient, and hostile behaviors toward authority figuresauthority figures

Conduct Disorder (CD)- Repetitive pattern of violating the basic Conduct Disorder (CD)- Repetitive pattern of violating the basic rights of others/ major age-appropriate social norms or rules are rights of others/ major age-appropriate social norms or rules are violatedviolated

Mood disorders (depression/bipolar disorder)- check family Mood disorders (depression/bipolar disorder)- check family history!history!

Poor outcome in co-morbid teens (higher risk for suicide)Poor outcome in co-morbid teens (higher risk for suicide)Anxiety Disorders- 25% or moreAnxiety Disorders- 25% or moreLearning Disorders- up to 60% in non-PCP settingsLearning Disorders- up to 60% in non-PCP settings

Especially Reading DisorderEspecially Reading Disorder

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Practice Guidelines*Practice Guidelines*

In children who have good primary care, other In children who have good primary care, other diagnostic tests are not diagnostic tests are not routinelyroutinely indicated indicatedEEG’s indicated only if a history of seizure d/o or EEG’s indicated only if a history of seizure d/o or

clinically significant lapses in consciousness existsclinically significant lapses in consciousness existsContinuous Performance Tests (CPT’s) are useful Continuous Performance Tests (CPT’s) are useful

in research settings onlyin research settings onlymeasures of vigilance / distractibility which have low measures of vigilance / distractibility which have low

odds ratios in differentiating children with and without odds ratios in differentiating children with and without ADHDADHD

1919

Practice Guidelines*Practice Guidelines*

SummarySummaryUse explicit criteria for diagnosisUse explicit criteria for diagnosisObtain history from more than 1 settingObtain history from more than 1 setting

sx must be severe enough to cause functional sx must be severe enough to cause functional impairmentimpairment

Screen for co-existing conditionsScreen for co-existing conditionsMay need 2-3 visits for full work-upMay need 2-3 visits for full work-up

parent and teacher questionnaires may be faxed parent and teacher questionnaires may be faxed for efficiencyfor efficiencyConnor’s scales, other ADHD rating scalesConnor’s scales, other ADHD rating scales

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Heterogenous condition, many Heterogenous condition, many causes*causes*

Final common pathwayFinal common pathwayfactors include:factors include:

brain structure / functional abnormalitiesbrain structure / functional abnormalitiesfamily / genetic factorsfamily / genetic factorsprenatal / perinatal factorsprenatal / perinatal factors

Maternal smoking and alcohol useMaternal smoking and alcohol useneurotoxinsneurotoxinspsychosocial stressors and combined factorspsychosocial stressors and combined factors

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Neuroimaging*Neuroimaging*

MRIMRI Loss of the normal L > R asymmetry, smaller brain Loss of the normal L > R asymmetry, smaller brain

volumes of specific structures, esp. L caudate, smaller volumes of specific structures, esp. L caudate, smaller white matter vol of R frontal lobewhite matter vol of R frontal lobe

PFC, BG--both rich in DA receptorsPFC, BG--both rich in DA receptors 5-10% decrease in volume5-10% decrease in volume

Decreased volume of anterior-superior hemisphereDecreased volume of anterior-superior hemisphere 5% decrease in R cerebellar volume, 4% reduction in 5% decrease in R cerebellar volume, 4% reduction in

intracranial volume; Unaffected siblings: up to 9% intracranial volume; Unaffected siblings: up to 9% decrease in selected prefrontal and occipital areasdecrease in selected prefrontal and occipital areas

Durston, et al (2004): Durston, et al (2004): J Amer Acad Child Adol PsychiatryJ Amer Acad Child Adol Psychiatry; 43(3); ; 43(3); 332-340332-340

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Legal Rights of the Student and Legal Rights of the Student and Obligations of the School District* Obligations of the School District*

((adapted from Robinadapted from Robin, , 19981998)) IDEA, Part B (1990)IDEA, Part B (1990)

This law entitles student to an Individualized Education This law entitles student to an Individualized Education Plan (IEP) as part of a “Special Education” planPlan (IEP) as part of a “Special Education” plan

Section 504 of the Rehabilitation Act of 1973Section 504 of the Rehabilitation Act of 1973 This law entitles student to classroom modifications in This law entitles student to classroom modifications in

the mainstream classroom (not “Special Ed”) the mainstream classroom (not “Special Ed”) Americans with Disabilities Act (1990)Americans with Disabilities Act (1990) For excellent up-to-date discussions of Special For excellent up-to-date discussions of Special

Education laws, including the No Child Left Education laws, including the No Child Left Behind Act, IDEA, and Section 504, seeBehind Act, IDEA, and Section 504, see www.schwablearning.orgwww.schwablearning.org

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IDEA, Pt B*IDEA, Pt B*

Requires public schools in the US to Requires public schools in the US to provide a provide a free and appropriate free and appropriate educationeducation for all children with disabilities for all children with disabilitiesEvaluation must show that the child has one Evaluation must show that the child has one

or more specific mental or physical or more specific mental or physical impairments, and these must be severe impairments, and these must be severe enough to warrant special educationenough to warrant special education

2626

IDEA, Pt B*IDEA, Pt B*

Children/ teens with ADHD may get Children/ teens with ADHD may get special ed services under 3 categories:special ed services under 3 categories:Specific LDSpecific LDEmotional disturbance (ED)Emotional disturbance (ED)Other health impaired (OHI)Other health impaired (OHI)

2727

Section 504*Section 504*

Rehab Act of 1973: A civil rights law that Rehab Act of 1973: A civil rights law that prohibits discrimination, in fed. funded prohibits discrimination, in fed. funded programs, solely based on disabilities, for programs, solely based on disabilities, for otherwise qualified persons.otherwise qualified persons.

No specific disability categories No specific disability categories Broadly defines disability as a “physical or Broadly defines disability as a “physical or

mental impairment which limits one or more mental impairment which limits one or more life activities”, including learning.life activities”, including learning.

2828

Psychoeducational Interventions*Psychoeducational Interventions*

Cognitive-Behavioral TreatmentCognitive-Behavioral Treatment Impulse controlImpulse control Anger managementAnger management

Classroom strategies and modificationsClassroom strategies and modifications FBAs (Functional Behavior Assessments)FBAs (Functional Behavior Assessments) 504 / IEP specifics504 / IEP specifics

Parent Education and EmpowermentParent Education and Empowerment www.parentshelpingparents.comwww.parentshelpingparents.com www.schwablearning.orgwww.schwablearning.org www.schoolpsychiatry.orgwww.schoolpsychiatry.org

2929

ADHD Treatments (Medication ADHD Treatments (Medication options)*options)*

Teaching PointsTeaching PointsWarnings about ADHD drugs should NOT Warnings about ADHD drugs should NOT

dissuade providers from using these drugsdissuade providers from using these drugsPsychostimulants remain the drugs of choice Psychostimulants remain the drugs of choice

for ADHDfor ADHDIt is important to “fine tune” medications by It is important to “fine tune” medications by

ascertaining effects over the dayascertaining effects over the day

3030

Warnings about ADHD drugs*Warnings about ADHD drugs*

12/04 Strattera: black box warning about possible hepatitis following 2 12/04 Strattera: black box warning about possible hepatitis following 2 reports of hepatitisreports of hepatitis

2/05 Adderall:FDA Alert- should not be used in individuals with underlying 2/05 Adderall:FDA Alert- should not be used in individuals with underlying cardiac abnormalities following 12 sudden unexpected deaths over time cardiac abnormalities following 12 sudden unexpected deaths over time Adderall in USA; only XR available in Canada and pulled from marketAdderall in USA; only XR available in Canada and pulled from market

6/05 Ped Adv Com of FDA-Will delay labeling change to all MPH products of 6/05 Ped Adv Com of FDA-Will delay labeling change to all MPH products of side effects of psychiatric (visual hallucination, psychosis, aggression) and side effects of psychiatric (visual hallucination, psychosis, aggression) and cardiovascular until amphetamines and atomoxetine also evaluated in early cardiovascular until amphetamines and atomoxetine also evaluated in early 20062006

6/05 Lilly observed increase in aggression and hostility “not statistically 6/05 Lilly observed increase in aggression and hostility “not statistically significant”, but will add information to Strattera label voluntarilysignificant”, but will add information to Strattera label voluntarily

3131

Warnings about ADHD drugs*Warnings about ADHD drugs*

10/05 Canada re-allowed Adderall XR back on market10/05 Canada re-allowed Adderall XR back on market

11/05 FDA requires Black Box warning on Strattera for 11/05 FDA requires Black Box warning on Strattera for increased risk of suicidality 4/1000increased risk of suicidality 4/1000

2-3/06 FDA advisory committee recommends black box 2-3/06 FDA advisory committee recommends black box warnings for CV risk on psychostimulantswarnings for CV risk on psychostimulants Committee votes only a parent guide and NOT a black box Committee votes only a parent guide and NOT a black box

warningwarning

3/06 European review highlights increased risk of seizures and 3/06 European review highlights increased risk of seizures and QTc prolongation with StratteraQTc prolongation with Strattera

3232

Special Issues: Pharmacotherapy in Youth*Special Issues: Pharmacotherapy in Youth*

Clinician must have good working alliance with both the patient AND the Clinician must have good working alliance with both the patient AND the parents (a dual alliance)parents (a dual alliance)

Children and (especially) teens may be reluctant consumersChildren and (especially) teens may be reluctant consumers

Children should be told that they may not recognize changes in Children should be told that they may not recognize changes in themselves before the first medication trialthemselves before the first medication trial

Importance of school placement and teacher-doctor allianceImportance of school placement and teacher-doctor alliance

Each school may have different requirements for medicating childrenEach school may have different requirements for medicating children

From MTA study (discussed later), parents recognize side effects and From MTA study (discussed later), parents recognize side effects and teachers recognize efficacyteachers recognize efficacy

3333

ADHD Treatments*ADHD Treatments*

MTA study: MTA study: Arch Gen PsychiatryArch Gen Psychiatry Vol 56, Vol 56, 1073-1086, Dec 19991073-1086, Dec 1999579 children with ADHD-CT; 7-9.9 yrs; 6 sites; 579 children with ADHD-CT; 7-9.9 yrs; 6 sites;

14 month parallel-design14 month parallel-design4 different treatment groups:4 different treatment groups:

Medication mgmnt (titration plus 30” monthly Medication mgmnt (titration plus 30” monthly visits)visits)

Intensive behav treatment (parent, school, child Intensive behav treatment (parent, school, child components)components)

Optimal combination of bothOptimal combination of both““Usual” community careUsual” community care

3434


MTA study: MTA study: conclusionsconclusionsAll 4 groups showed sizable reduction in All 4 groups showed sizable reduction in

symptoms over timesymptoms over timeADHD symptomsADHD symptoms: Combo. and med-only : Combo. and med-only

groups had significantly greater improvement groups had significantly greater improvement than those given intensive behav tx or ”usual” than those given intensive behav tx or ”usual” community care (UCC)community care (UCC)

ADHD with co-morbid anxiety disorder: ADHD with co-morbid anxiety disorder: behavioral treatment was similar to behavioral treatment was similar to medication tx, and both were superior to UCCmedication tx, and both were superior to UCC

3535

MTA study: cont’d.*MTA study: cont’d.*

Combined behavioral intervention and Combined behavioral intervention and stimulant medication--(multimodal treatment), stimulant medication--(multimodal treatment), yielded no statistically significantly greater yielded no statistically significantly greater benefits than medication management “alone” benefits than medication management “alone” for the core symptoms of ADHDfor the core symptoms of ADHD

Note that the “medication management” in this Note that the “medication management” in this study occurred for 30 minutes, 1x per monthstudy occurred for 30 minutes, 1x per month ““usual community care” average for visit frequency usual community care” average for visit frequency

was 1-2x per yearwas 1-2x per year

3636


MTA study: cont’d.MTA study: cont’d. Non-ADHD symptomsNon-ADHD symptoms: (social skills, parent-child : (social skills, parent-child

relations, oppositional-aggressive behavior, relations, oppositional-aggressive behavior, internalizing symptoms, academic achievement)internalizing symptoms, academic achievement)

The 3 MTA-delivered treatments were very similar, with the The 3 MTA-delivered treatments were very similar, with the combined treatment arm being consistently superior to UCC.combined treatment arm being consistently superior to UCC.

Highly anxious children with ADHD may represent a Highly anxious children with ADHD may represent a subgroup of children with unique treatment needssubgroup of children with unique treatment needs

13 % placebo response in MTA study13 % placebo response in MTA study May have been related to alliance with MD and research May have been related to alliance with MD and research

teamteam

3737


MTA study: 2 year follow-up MTA study: 2 year follow-up ((PEDIATRICSPEDIATRICS ,113 (4); April 2004, ,113 (4); April 2004, pp. 762-769)pp. 762-769)

- Consistent use of stimulant medication was associated Consistent use of stimulant medication was associated with maintenance of effectiveness but continued “mild with maintenance of effectiveness but continued “mild growth suppression” (1 cm per year over 2 years). growth suppression” (1 cm per year over 2 years).

- Further follow-up will help to address question of growth Further follow-up will help to address question of growth (ultimate ht. suppression vs. longer time to finish (ultimate ht. suppression vs. longer time to finish growing)growing)

- Medication holidays may be prudent clinical practice Medication holidays may be prudent clinical practice (summertime, holidays)(summertime, holidays)

3838

ADHD Treatments* (medication ADHD Treatments* (medication options)options)

Established TreatmentsEstablished Treatments Psychostimulants (1Psychostimulants (1stst line) line) Atomoxetine (1Atomoxetine (1stst line) line) Bupropion (2Bupropion (2ndnd line) line) TCAs (2TCAs (2nd-nd- 3 3rdrd line) line)

Probable EfficacyProbable Efficacy ModafinilModafinil Alpha-2 agonistsAlpha-2 agonists

3939


Possible efficacyPossible efficacy Omega-3, -6 Fatty Acids (Fish Oil, Flax Seed Oil)Omega-3, -6 Fatty Acids (Fish Oil, Flax Seed Oil) VenlafaxineVenlafaxine Beta-blockersBeta-blockers

Effective, but impractical: MAOIsEffective, but impractical: MAOIs LikelyLikely ineffectiveineffective

SSRIsSSRIs CaffeineCaffeine St. John’s WortSt. John’s Wort

4040

Stimulants*Stimulants*

““stimulate” certain areas of the brain to stimulate” certain areas of the brain to focus betterfocus betterFDA classifies a substance as “psychostimulant” FDA classifies a substance as “psychostimulant”

if nucleus accumbens is activatedif nucleus accumbens is activated in use for “behavioral disorders” in children in use for “behavioral disorders” in children

since 1930’ssince 1930’smany studies to document safety and many studies to document safety and

efficacyefficacy70-85% response rate70-85% response rate

do not use this to confirm diagnosis!do not use this to confirm diagnosis!

4141


benefits: improved focus, concentration, benefits: improved focus, concentration, attention span; reduced hyperactivity, attention span; reduced hyperactivity, impulsivity, and fidgetingimpulsivity, and fidgeting

side effects: irritability, stomachache, headache, side effects: irritability, stomachache, headache, dysphoria, zoned-out effect, appetite dysphoria, zoned-out effect, appetite suppression, sleep problems, height velocity suppression, sleep problems, height velocity slow-down (<10%)slow-down (<10%)

Amphetamine formulations may produce more Amphetamine formulations may produce more sleep/ appetite problems, especially at higher sleep/ appetite problems, especially at higher dosesdoses

4242


Special considerationSpecial consideration Motor ticsMotor tics DepressionDepression Anxiety d/o (children w/ co-morbid anxiety may improve Anxiety d/o (children w/ co-morbid anxiety may improve

on MPH, according to MTA study)on MPH, according to MTA study) Seizure d/oSeizure d/o Children under 6 years old may be safely treated, starting Children under 6 years old may be safely treated, starting

with methylphenidate, once all psychosocial treatments with methylphenidate, once all psychosocial treatments have been implementedhave been implemented

PATS (Pre-school ADHD Treatment Study) is one of many to PATS (Pre-school ADHD Treatment Study) is one of many to document safety and efficacydocument safety and efficacy

Young children may be more sensitive to side effectsYoung children may be more sensitive to side effects Consider weight-based dosing for children under 25 kg: 1mg/kg/day Consider weight-based dosing for children under 25 kg: 1mg/kg/day

(MPH); 0.5 mg/kg/day (AMPH)(MPH); 0.5 mg/kg/day (AMPH)

4343

Methylphenidate FormulationsMethylphenidate FormulationsBrand Type Dosage

forms (mg) Est. duration (hrs)

Max daily dose [mg] Range 0.3-1.0mg/kg/day

Generic IR 5,10,20 2.5 - 4 [60]

Ritalin IR SR LA***

5,10,20 20 20

2.5 - 4 6 - ? 8-10

[60]

Methylin IR* ER

5,10,20 5,10,20

2.5 - 4 6 -8

[60]

Focalin IR XR***

2.5,5,10 5, 10, 15, 20

3-5 8-10

[20-30]

Metadate ER CD***

10,20 20

6-8 8 -12

[60]

Concerta ER 18, 27,36,54 10 - 12 [72]

Daytrana patch 10, 15, 20, 30 9-12 [30]

[ ] Some patients may tolerate higher doses. * Available in chewable tablets and liquid *** May be sprinkled on food Chart adapted from Glen R. Elliott, PhD, MD

4444

Amphetamine FormulationsAmphetamine Formulations

Brand Type Dosage forms (mg)

Est. duration (hrs)

Max daily dose (mg) Range 0.15-0.5 mg/kg/day

Generic IR 5,10,20 3-6 40 *

Dexedrine IR Spansules**

5,10 5, 10, 15

4-5 5-9

40 *

Adderall IR XR**

5, 7.5, 10, 12.5, 15, 20, 30 5-30 mg , (in 5-mg increments)

4-6 8-10

40*

Vyvanse Lisdex- amfetamine

2.5,5,10 5, 10, 15, 20

8-10 70

*Some patients will tolerate higher doses. **may be sprinkled on food Chart adapted from Glen R. Elliott, PhD, MD

4545

Adderall XR*-delivers mixed

salts using immediateand time-released

beads:50% immediate

50% delayed

Concerta-delivers MPH

using immediate release coating and

delayed release osmotic mechanism:

22% immediate78% delayed

Metadate CD-biphasic delivery of

MPH using immediateand delayed release beads

in capsule:30% immediate

70% delayed

Ritalin LA-biphasic delivery of MPH using immediate

and delayed release beadsin capsule:

50% immediate50% delayed

Focalin XR-biphasic delivery of

dextro MPH using immediateand delayed release beads

in capsule50% immediate

50% delayed

(note: only the d-version of MPH is active, thus only 1/2 the usual MPH dose is used)

4646

Match the formulation with the Match the formulation with the needs of the patient and family*needs of the patient and family*

Have to know when youth “needs” the Have to know when youth “needs” the psychostimulant (e.g., early in AM for school psychostimulant (e.g., early in AM for school only, or including homework, peer activities, only, or including homework, peer activities, week-ends)week-ends)

Parent and teen sometimes have definite Parent and teen sometimes have definite preferences for one or another, and so do HMOs preferences for one or another, and so do HMOs

Train parents to observe efficacy and side Train parents to observe efficacy and side effects through the day and into the eveningeffects through the day and into the evening

4747

How to initiate dosing*How to initiate dosing*

Generally not by weight, unless patients are less than 25 Generally not by weight, unless patients are less than 25 kg (0.3- 1mg/kg/d for MPH)kg (0.3- 1mg/kg/d for MPH) (0.15 - 0.5 mg/kg/d for AMPH)(0.15 - 0.5 mg/kg/d for AMPH)

Titrate to efficacy or intolerable side effects: start at 5 Titrate to efficacy or intolerable side effects: start at 5 mg MPH or 2.5 mg AMPmg MPH or 2.5 mg AMP Increase by 5 mg MPH, or 2.5 mg AMP every 3-5 days to first Increase by 5 mg MPH, or 2.5 mg AMP every 3-5 days to first

target dose, decided upon by doctor and familytarget dose, decided upon by doctor and family Get weekly reports and adjust upward, checking for side effects Get weekly reports and adjust upward, checking for side effects

and efficacyand efficacy

4848

The Art of Fine tuning*The Art of Fine tuning*

Must have accurate info about Must have accurate info about child/teen’s performance “over the child/teen’s performance “over the day”; use scales and listen to teachers: day”; use scales and listen to teachers: titrate as needed titrate as needed

Can combine short and long-acting Can combine short and long-acting preparationspreparationsif dysphoric at days end, add MPH to if dysphoric at days end, add MPH to

Concerta at the end of the school day (no Concerta at the end of the school day (no later than 3:30PM); Dex to Dex-spansules later than 3:30PM); Dex to Dex-spansules at the start of the day because of delayed at the start of the day because of delayed effect of spansuleseffect of spansules

4949

The Art of Fine-tuning –II*The Art of Fine-tuning –II*

If only partial efficacy with stimulants, can If only partial efficacy with stimulants, can “mix and match” with other anti-ADHD “mix and match” with other anti-ADHD drugs (e.g., clonidine / guanfacine, drugs (e.g., clonidine / guanfacine, bupropion, atomoxetine TCAs)bupropion, atomoxetine TCAs)

Inform family, and be vigilant about Inform family, and be vigilant about checking for additive sympathomimetic checking for additive sympathomimetic side effectsside effects

5050

Common errors in dosing Common errors in dosing psychostimulants*psychostimulants*

Failure to increase dosing slowly to maximum if no side Failure to increase dosing slowly to maximum if no side effects (MTA study showed lower dosing in community effects (MTA study showed lower dosing in community samplesample

Beginning with a dose that is too highBeginning with a dose that is too high ““Start low and go especially slow” with patients who are Start low and go especially slow” with patients who are

developmentally delayeddevelopmentally delayed Not assessing the duration of action; (may need to “bunch Not assessing the duration of action; (may need to “bunch

up “ dosing with IR formulations)up “ dosing with IR formulations) Failure to use another psychostimulant if the first or Failure to use another psychostimulant if the first or

second trial failssecond trial fails Failure to use input from schoolFailure to use input from school

5151

Serious side effects of Serious side effects of psychostimulants*psychostimulants*

Sudden cardiac deathSudden cardiac death Anecdotal, but not irrelevantAnecdotal, but not irrelevant Cases thus far have been primarily in patients with pre-Cases thus far have been primarily in patients with pre-

existing cardiac conduction defectsexisting cardiac conduction defects Ask about history of sudden tachycardia, fainting, and Ask about history of sudden tachycardia, fainting, and

family history of sudden cardiac death prior to initiatingfamily history of sudden cardiac death prior to initiating 30+ cases of psychosis or formal hallucinations: 30+ cases of psychosis or formal hallucinations:

discontinue the medicationdiscontinue the medication Growth Suppression (MTA 2004) effects are likely to be Growth Suppression (MTA 2004) effects are likely to be

made up in late teens or by drug holidays; especially at made up in late teens or by drug holidays; especially at risk, those with nausea and vomitingrisk, those with nausea and vomiting Plot heights every 3 months to ensure proper growth velocityPlot heights every 3 months to ensure proper growth velocity

5252

Mild or moderate tics occur in a significant number of patients with or Mild or moderate tics occur in a significant number of patients with or without ADHD pharmacotherapywithout ADHD pharmacotherapy 5-18% of schoolchildren will experience a simple or complex tic in their 5-18% of schoolchildren will experience a simple or complex tic in their

lifetimelifetime Tics during ADHD treatment may improve even while Tics during ADHD treatment may improve even while

psychostimulants are used; discontinue only if seriouspsychostimulants are used; discontinue only if serious

Lipkin et alLipkin et al, in a review of 122 children treated with stimulant medication , in a review of 122 children treated with stimulant medication found 9% developed transient tics and <1% developed chronic ticsfound 9% developed transient tics and <1% developed chronic tics

Lowe et al. JAMA 1982;247:1729.Sverd et al. JAACAP 1989;28:574.

Erenberg et al. Neurology 1985;35:1346.Lipkin et al. Arch Pediatr Adolesc Med 1994;148:859.

Tics and ADHD* Tics and ADHD* (adapted from review by Plizska, (adapted from review by Plizska, 2006)2006)

5353

Tics and ADHD* Tics and ADHD* (adapted from review by (adapted from review by Plizska, 2006)Plizska, 2006)

Many children with tics and ADHD can tolerate stimulants without an Many children with tics and ADHD can tolerate stimulants without an increase in ticsincrease in tics

Law & SchacharLaw & Schachar (1999):(1999): 12-month study, 91 children 12-month study, 91 childrenMPH treatment did not produce significantly more tics than MPH treatment did not produce significantly more tics than

placebo in children with or without mild-to-moderate placebo in children with or without mild-to-moderate preexisting tic disorderpreexisting tic disorder

Gadow et al (1999):Gadow et al (1999): 24-month study, 34 children with 24-month study, 34 children with ADHD and tic disorder or Tourette’s syndrome ADHD and tic disorder or Tourette’s syndrome

stimulant treatment was effective in controlling ADHD stimulant treatment was effective in controlling ADHD symptoms without adversely affecting tics symptoms without adversely affecting tics

5454

Induction or Exacerbation of Tics* Induction or Exacerbation of Tics* (adapted from review by Plizska, 2006)(adapted from review by Plizska, 2006)

Tics are usually transientTics are usually transient Rarely do patients develop a chronic tic disorderRarely do patients develop a chronic tic disorder

When tics do occur or are worsenedWhen tics do occur or are worsened Decrease doseDecrease dose Switch to another stimulantSwitch to another stimulant Add adjunctive drug to treat tics Add adjunctive drug to treat tics

Clonidine / guanfacineClonidine / guanfacine Try nonstimulant medicationTry nonstimulant medication

AtomoxetineAtomoxetine ModafinilModafinil

5555

ADHD Treatments* (other medication ADHD Treatments* (other medication options)options)

AtomoxetineAtomoxetinePotent norepinephrine (NE) reuptake inhibitorPotent norepinephrine (NE) reuptake inhibitor

highly selectivehighly selectiveinhibits presynaptic NE transporterinhibits presynaptic NE transporter

5757

ADHD Treatments (medication ADHD Treatments (medication options)options)

Atomoxetine Atomoxetine (not to be confused with (not to be confused with Tamoxifen)Tamoxifen) Michelson, et al (2001) : n=297, ages 8-18, 71 % Michelson, et al (2001) : n=297, ages 8-18, 71 %

male; 67% ADHD-CT; 8-week randomized prospective male; 67% ADHD-CT; 8-week randomized prospective controlled studycontrolled study

Participants were moderately -to-severely impaired Participants were moderately -to-severely impaired prior to tx.prior to tx.

Results showed superior response to placebo (65% Results showed superior response to placebo (65% response rate)response rate)

ADHD symptomsADHD symptomsMeasures of social and family functioning Measures of social and family functioning

5858


AtomoxetineAtomoxetineTotal database (Lilly) of several thousand Total database (Lilly) of several thousand

pediatric and adult patients with ADHDpediatric and adult patients with ADHDCommon side effects: Dizziness, drowsiness, Common side effects: Dizziness, drowsiness,

dyspepsia, decreased appetitedyspepsia, decreased appetiteLess common, but not rare (>2%)Less common, but not rare (>2%)

Depression, tremor, early AM awakening, pruritus (generalized Depression, tremor, early AM awakening, pruritus (generalized itching)itching)

Adult patients: Possible Sexual dysfunction; No abuse Adult patients: Possible Sexual dysfunction; No abuse potential (no activation of dopamine in nucleus potential (no activation of dopamine in nucleus accumbens)accumbens)

5959

Atomoxetine*, cont’dAtomoxetine*, cont’d

CYP2D6 substrate CYP2D6 substrate Use cautiously when other medicines are used (eg. paroxetine, fluoxetine, Use cautiously when other medicines are used (eg. paroxetine, fluoxetine,

quinidine)quinidine) Dose: 0.5 mg/kg/day—1.2 mg/kg/day; Max dose 1.4 mg/kg/day or 100mg Dose: 0.5 mg/kg/day—1.2 mg/kg/day; Max dose 1.4 mg/kg/day or 100mg

(whichever is less)(whichever is less) Assessment of liver function prior to start is optional; monitor for Assessment of liver function prior to start is optional; monitor for

hepatotoxicityhepatotoxicity

Black Box warningBlack Box warning re: teen patients with suicidal thinking re: teen patients with suicidal thinking 5/1357 patients with suicidal thinking during initial trials5/1357 patients with suicidal thinking during initial trials

1 of these 5 actually attempted suicide (unsuccessfully)1 of these 5 actually attempted suicide (unsuccessfully)

Monitor height, weight, pulse and BPMonitor height, weight, pulse and BP Potential exists for decreases in growth ( up to 0.5cm per year, and increases in HR and BP)Potential exists for decreases in growth ( up to 0.5cm per year, and increases in HR and BP)

May be used QD or BIDMay be used QD or BID Time to Cmax is 1-2 hoursTime to Cmax is 1-2 hours Duration of action is 6-10 hours (may be up to 24 hours)Duration of action is 6-10 hours (may be up to 24 hours) Allow 6-8 weeks for full effect!Allow 6-8 weeks for full effect!

6060

ADHD Treatments* (other ADHD Treatments* (other medication options)medication options)

Tricyclic Antidepressants (TCAs)Tricyclic Antidepressants (TCAs)30+ randomized controlled studies show 30+ randomized controlled studies show

efficacy in childrenefficacy in childrenimipramine, amitryptiline, desipramine, imipramine, amitryptiline, desipramine,

clomipramineclomipramineuncontrolled studies show benefit of uncontrolled studies show benefit of

nortryptiline, protryptilinenortryptiline, protryptiline

6161


Tricyclic Antidepressants (TCAs)Tricyclic Antidepressants (TCAs) strong effects on H/I symptomsstrong effects on H/I symptoms weaker cognitive benefits than stimulantsweaker cognitive benefits than stimulantsDosing/ monitoringDosing/ monitoring

Use grad dose elevation/ LOTSA drug interax!Use grad dose elevation/ LOTSA drug interax! Imipramine most widely usedImipramine most widely usedMost will respond to less than 5mg/kg/dayMost will respond to less than 5mg/kg/day

many to 1-2mg/kg/daymany to 1-2mg/kg/daystart at 50 mg @ HS// level @ 7-10 daysstart at 50 mg @ HS// level @ 7-10 daysDo not exceed 300 ng/mlDo not exceed 300 ng/ml

Monitor BP, EKGs: Monitor BP, EKGs: QTc < 0.44ms, PR< 200ms, QRS < 120msQTc < 0.44ms, PR< 200ms, QRS < 120ms

6262

Cardiovascular parameters for TCAs: Cardiovascular parameters for TCAs: When to Call A Cardiology Consult *!When to Call A Cardiology Consult *!

Resting heart Resting BP PR QTcResting heart Resting BP PR QTc beats/minbeats/min = or > = o r> = or > = or >= or > = o r> = or > = or >< 10 yrs 110 140/90 or 135/85 0.18 0.44< 10 yrs 110 140/90 or 135/85 0.18 0.44 > 1/2 time 3 wks> 1/2 time 3 wks

>10 yrs 100 150/95 or 140/85 0.20 0.44>10 yrs 100 150/95 or 140/85 0.20 0.44 > 1/2 time 3 wks> 1/2 time 3 wksAdapted from Rye and Ryan: Adapted from Rye and Ryan: Child and Adolesc Psychiatric Clinics NAChild and Adolesc Psychiatric Clinics NA 4:275, 4:275,

19951995

6363

Tricyclic Antidepressants (TCAs)Tricyclic Antidepressants (TCAs)

Clomipramine (Clomipramine (non-routine in kidsnon-routine in kids))non-selective SRInon-selective SRIdata to show efficacy, but side effects limit data to show efficacy, but side effects limit

useusepossible use in co-morbid OCDpossible use in co-morbid OCDHigh seizure risk (1.5% annual risk in adults)High seizure risk (1.5% annual risk in adults)

DesipramineDesipramineStill used in adults Still used in adults 6 published cases of sudden death in children6 published cases of sudden death in children

6464

TCAs drug interactionsTCAs drug interactions

Very complicated, must be vigilant when using Very complicated, must be vigilant when using polypharmacypolypharmacy

TCAs demethylated by variety of CYPs and then TCAs demethylated by variety of CYPs and then hydroxylated via CYP2D6 hydroxylated via CYP2D6

Paroxetine/ fluoxetine inhibit CYP2D6, Paroxetine/ fluoxetine inhibit CYP2D6, thus decrease thus decrease clearance up to 400% of CYP2D6 substrates, including clearance up to 400% of CYP2D6 substrates, including TCAsTCAs

Sertraline/citalopram decrease clearance 25% of Sertraline/citalopram decrease clearance 25% of CYP2D6 substratesCYP2D6 substrates

6565

CMAP-ADHD*CMAP-ADHD*

http://www.mhmr.state.tx.us/centraloffice/http://www.mhmr.state.tx.us/centraloffice/medicaldirector/adhdalgo.pdfmedicaldirector/adhdalgo.pdf

4 algorithms*: ADHD, with tics, with MDD and 4 algorithms*: ADHD, with tics, with MDD and with IEDwith IED

Tactic Tables: Dosing schedules for Tactic Tables: Dosing schedules for Stimulants,TCAs,Bupropion, Alpha Agonists and Stimulants,TCAs,Bupropion, Alpha Agonists and SSRIsSSRIs

7070

Other medication options*Other medication options*

Bupropion (Wellbutrin / Zyban)Bupropion (Wellbutrin / Zyban)Minimal 5-HT effectsMinimal 5-HT effectsInhibits NE, DA uptakeInhibits NE, DA uptakeMay have special use with comorbid May have special use with comorbid

depression or substance abusedepression or substance abuse1 open and 3 controlled studies in children1 open and 3 controlled studies in children

not quite as robust an effect as stimulantsnot quite as robust an effect as stimulants

7171

Bupropion, cont’d.*Bupropion, cont’d.*

Side effectsSide effects skin rashskin rash seizures (lower with SR preparation)seizures (lower with SR preparation)

0.3%-0.4%; risk increases with doses> 450 mg Total Daily 0.3%-0.4%; risk increases with doses> 450 mg Total Daily DoseDose

psychosis, agitationpsychosis, agitation sleep problemssleep problems appetite suppressionappetite suppression

May have paradoxical beneficial effect on appetite when May have paradoxical beneficial effect on appetite when combined with stimulants combined with stimulants

Callaghan, Callaghan, JAACAPJAACAP, July 1999, July 1999

7272

Venlafaxine (Effexor)*Venlafaxine (Effexor)*

Selective Inhibition of NE and 5-HTSelective Inhibition of NE and 5-HT Adults: 3 open series and a case report suggest Adults: 3 open series and a case report suggest

therapeutic effectstherapeutic effects Youths: 1 case series (n=16), 1 case reportYouths: 1 case series (n=16), 1 case report

more benefits on behavioral than cognitive symptomsmore benefits on behavioral than cognitive symptoms anecdotal reports: useful in OCD, perseveration, anecdotal reports: useful in OCD, perseveration,

depression, anxiety, agitationdepression, anxiety, agitation Recently fallen out of favor due to concerns about Recently fallen out of favor due to concerns about

suicidal thinkingsuicidal thinking

7373

Clonidine (Catapres)*Clonidine (Catapres)*

alpha-2 adrenergic agonistalpha-2 adrenergic agonistmay have role for H-I symptoms and may have role for H-I symptoms and

aggression (not inattention)aggression (not inattention)special utility in DD populationspecial utility in DD population

placebo-med differences have been found placebo-med differences have been found in small controlled studiesin small controlled studies

side effects often limit its usefulnessside effects often limit its usefulnessCV, sedationCV, sedation

7474

Clonidine (Catapres)Clonidine (Catapres)

Dose:Dose: Start with 0.05 mg @ HSStart with 0.05 mg @ HS Typical range is 0.05-0.2 mg, BID-QIDTypical range is 0.05-0.2 mg, BID-QID max daily dose 0.9 mgmax daily dose 0.9 mg

Must monitor BP, other CV parametersMust monitor BP, other CV parameters Possible bradycardiaPossible bradycardia rebound tachycardia and HTN rebound tachycardia and HTN

children between doses children between doses if d/c’d abruptlyif d/c’d abruptly

if tx’d for more than 1 month, d/c at a rate of 0.05 mg q3-7 daysif tx’d for more than 1 month, d/c at a rate of 0.05 mg q3-7 days

7575

Clonidine (Catapres)Clonidine (Catapres)

Relative contraindication : DepressionRelative contraindication : Depression MPH/ CLON combinationMPH/ CLON combination

may be very helpful, esp. w/ comorbid insomniamay be very helpful, esp. w/ comorbid insomnia 1994: 40% of pts w/ ADHD tx’d with CLON were also 1994: 40% of pts w/ ADHD tx’d with CLON were also

on stimulants.on stimulants. 3 fatalities, 1 LTE in kids on MPH/ CLON3 fatalities, 1 LTE in kids on MPH/ CLON

See See JAACAPJAACAP 38:5, May 1999, pp614-622, for debate on this 38:5, May 1999, pp614-622, for debate on this often-used combination often-used combination

Recent prospective studies from the Neurology literature Recent prospective studies from the Neurology literature MPH/CLON combo for tx of ADHD and tics MPH/CLON combo for tx of ADHD and tics NeurologyNeurology 2002;58:527-5362002;58:527-536 Total n= 160; no major safety issues in cross-over studies of up to 4 monthsTotal n= 160; no major safety issues in cross-over studies of up to 4 months Mean daily doses CLON 0.25 mg; MPH 25 mg Mean daily doses CLON 0.25 mg; MPH 25 mg

7676

Pre-treatment workup for Pre-treatment workup for ClonidineClonidine

Check for history of arrhythmias, relatives’ early Check for history of arrhythmias, relatives’ early sudden deathsudden death

Check for Raynaud’s Disease, Diabetes Mellitus Check for Raynaud’s Disease, Diabetes Mellitus ECG if indicated (Biederman 1999, Kofoed 1999, ECG if indicated (Biederman 1999, Kofoed 1999,

Oesterheld 1996)Oesterheld 1996) Orthostatic blood pressureOrthostatic blood pressure PulsePulse

7777

Clonidine:Side effectsClonidine:Side effects

CommonCommon Sedation, dry mouth, dizzinessSedation, dry mouth, dizziness Nighttime awakenings, nightmares, night terrorsNighttime awakenings, nightmares, night terrors

SeriousSerious Idiosyncratic aggravation of cardiac arrhythmiasIdiosyncratic aggravation of cardiac arrhythmias Danger of rebound hypertension if stopped suddenlyDanger of rebound hypertension if stopped suddenly Depression in about 5%Depression in about 5% HyperHyperglycemiaglycemia

No contraindication to use with psychostimulantsNo contraindication to use with psychostimulants, , as of 2008 as of 2008

7878

Guanfacine (Tenex)*Guanfacine (Tenex)*

Similar MOA to clonidine, with some impt receptor diffs:Similar MOA to clonidine, with some impt receptor diffs: alpha alpha 2A2A agonist, but weaker alpha agonist, but weaker alpha 11, alpha , alpha 2B2B, alpha , alpha 2C 2C activityactivity less beta-adrenergic, histamine, 5-HT, beta-endorphin, and DA less beta-adrenergic, histamine, 5-HT, beta-endorphin, and DA

effectseffects Less hypotension, sedation, rebound HTNLess hypotension, sedation, rebound HTN Longer duration, so less frequent dosing necessary (T Longer duration, so less frequent dosing necessary (T

1/2= 1/2= 17 hrs.); pks in 2-3 hrs17 hrs.); pks in 2-3 hrs start with 0.5 mg qD, then increase 0.5 mg q3-4 days if start with 0.5 mg qD, then increase 0.5 mg q3-4 days if

necessarynecessary optimal dosing: 2.5-3.5 mg TDD, div TID or QID.optimal dosing: 2.5-3.5 mg TDD, div TID or QID. MDD=4 mg/dayMDD=4 mg/day

May have role in inattention, impulsivity, ticsMay have role in inattention, impulsivity, tics

7979

Guanfacine (Tenex)Guanfacine (Tenex)

Sedation , BP changes are common (25-30%), Sedation , BP changes are common (25-30%), but usually transientbut usually transient

No reports of sudden death thus far.No reports of sudden death thus far.Monitor for behavioral activation/ disinhibitionMonitor for behavioral activation/ disinhibitionControlled studies underwayControlled studies underway

See Scahill, et al: See Scahill, et al: Am J PsychiatryAm J Psychiatry 158:7, July 2001 158:7, July 2001Long-acting form of guanfacine (Intuniv) will be Long-acting form of guanfacine (Intuniv) will be

available as a non-stimulant drug for ADHD for available as a non-stimulant drug for ADHD for children aged 6-17 years, possibly in 2008.children aged 6-17 years, possibly in 2008.

8080

Modafinil (Provigil)*Modafinil (Provigil)*

Wakefulness promoterWakefulness promoterMOA: Possible modulation of glutamate and MOA: Possible modulation of glutamate and

GABA, and/or an effect on orexin/hypocretin GABA, and/or an effect on orexin/hypocretin receptorsreceptorsResults in an increase in extracellular DA, NE, 5-Results in an increase in extracellular DA, NE, 5-

HTHTDifferent MOA than stimulantsDifferent MOA than stimulants

Schedule IV (cf. schedule II), thus fewer Schedule IV (cf. schedule II), thus fewer prescribing restrictionsprescribing restrictions

Therapeutic Dose range: 100-400 mg qAMTherapeutic Dose range: 100-400 mg qAM

8181

Modafinil (Provigil)Modafinil (Provigil)

Benefits: Improved mood, reaction time, logical Benefits: Improved mood, reaction time, logical reasoning, short term memoryreasoning, short term memory

Side effects: Headache, nausea, rhinitis, pharyngitis, Side effects: Headache, nausea, rhinitis, pharyngitis, dizziness, dry mouth, anorexia, insomniadizziness, dry mouth, anorexia, insomnia

Current FDA Indications: Narcolepsy in Pts 16 and olderCurrent FDA Indications: Narcolepsy in Pts 16 and older Duration 12-15 hoursDuration 12-15 hours Rugino Study (2003): 6 weeks; n=22; RPCTRugino Study (2003): 6 weeks; n=22; RPCT

100mg QD: Significant improvement vs. placebo; minimal side 100mg QD: Significant improvement vs. placebo; minimal side effects; no anorexiaeffects; no anorexia

Independent study (No Cephalon funding)Independent study (No Cephalon funding)

8282

Modafinil in ADHD Modafinil in ADHD (adapted from review by (adapted from review by

Pliszka, 2006)Pliszka, 2006)

Double blind, placebo controlled trialDouble blind, placebo controlled trial190 patients, ages 6-17 years190 patients, ages 6-17 years7 week trial, 2:1 randomization 7 week trial, 2:1 randomization

assignment to modafinil or placeboassignment to modafinil or placeboDose: < 30 kg: 340 mgDose: < 30 kg: 340 mg

30kg or heavier: 425 mg-fixed titration30kg or heavier: 425 mg-fixed titration

8383

Modafinil in ADHD*Modafinil in ADHD*

Submission to FDA in 2006 for Pediatric and Submission to FDA in 2006 for Pediatric and Adult ADHD indication with new trade name, Adult ADHD indication with new trade name, “Sparlon”, and 2 additional positive studies“Sparlon”, and 2 additional positive studies Rejected due to safety concerns over possible Rejected due to safety concerns over possible

Stevens-Johnson syndrome in 3 pediatric and 5 adult Stevens-Johnson syndrome in 3 pediatric and 5 adult patientspatients

8484

Adult ADHDAdult ADHD

Still regarded as “controversial”, despite presence of Still regarded as “controversial”, despite presence of continued morbidity in 50% or more of teens continued morbidity in 50% or more of teens transitioning to young adulthoodtransitioning to young adulthood

Diagnosis is primarily clinicalDiagnosis is primarily clinical Useful tools include Connors Adult ADHD Rating Scales Useful tools include Connors Adult ADHD Rating Scales

(CAARS), and Wender-Reimherr Adult ADD Scale (WRAADS)(CAARS), and Wender-Reimherr Adult ADD Scale (WRAADS) Self-assessment, Adult ADHD Self Report Scale (NYU)Self-assessment, Adult ADHD Self Report Scale (NYU)

http://www.med.nyu.edu/psych/assets/adhdscreen18.pdf DSM is only partially usefulDSM is only partially useful

Valid for children and teens onlyValid for children and teens onlySome items irrelevant for adults : “runs/climbs excessively; difficulty Some items irrelevant for adults : “runs/climbs excessively; difficulty

playing quietly”playing quietly”Adult dx “relies” on ADHD NOS, or “Residual type”Adult dx “relies” on ADHD NOS, or “Residual type”

8585

Adult ADHD Adult ADHD (McGough & Barkley, 2004)(McGough & Barkley, 2004)

Shortcomings of DSM-IV TR criteria: Shortcomings of DSM-IV TR criteria: Adult ADHD is Adult ADHD is classified as ADHD NOS in DSM-IV TR; Criteriaclassified as ADHD NOS in DSM-IV TR; Criteria do not do not taketake “ “additional major life settings” into account which additional major life settings” into account which may produce impairment yet would not be evident in may produce impairment yet would not be evident in children children General functioning within the larger organized community (e.g., General functioning within the larger organized community (e.g.,

participating in government, cooperating with others, abiding by participating in government, cooperating with others, abiding by laws, driving)laws, driving)

Financial management (e.g., banking, establishing and using Financial management (e.g., banking, establishing and using credit, forming contracts)credit, forming contracts)

Child rearing (providing protection, sustenance, financial and Child rearing (providing protection, sustenance, financial and social support, appropriate education, etc.)social support, appropriate education, etc.)

Marital functioningMarital functioning Routine health maintenance activities Routine health maintenance activities

8686


Laboratory-based measures in the diagnosis of Laboratory-based measures in the diagnosis of ADHDADHD SPECT, fMRI, CPT, PET useful currently SPECT, fMRI, CPT, PET useful currently for research for research

purposes onlypurposes only

ADHD remains a clinical diagnosisADHD remains a clinical diagnosis that is best that is best determined through careful history taking, determined through careful history taking, adherence to well-described clinical criteria, and adherence to well-described clinical criteria, and training in the differential diagnosis of adult training in the differential diagnosis of adult disorders disorders (McGough & Barkley, 2004)(McGough & Barkley, 2004)

8787

Summary for diagnosis: Adult ADHD Summary for diagnosis: Adult ADHD (McGough & Barkley, 2004)(McGough & Barkley, 2004)

Use rating scales that have been well standardized Use rating scales that have been well standardized in groups of adults (eg,CAARS (Connors Adult ADHD in groups of adults (eg,CAARS (Connors Adult ADHD Rating Scales), and WRAADS (Wender-Reimherr Rating Scales), and WRAADS (Wender-Reimherr Adult ADD Scale )Adult ADD Scale )

Given the lack of empirical support for 7 years as Given the lack of empirical support for 7 years as the age-of-onset criterion, clinicians should establish the age-of-onset criterion, clinicians should establish some evidence of symptoms and impairment before some evidence of symptoms and impairment before age 12 or initiation of pubertyage 12 or initiation of puberty

In assessing functional impairment, consider all In assessing functional impairment, consider all available information to confirm evidence of available information to confirm evidence of pervasive impairments over the lifespan, even if pervasive impairments over the lifespan, even if current complaints are limited to a single domaincurrent complaints are limited to a single domain

8888


Clinicians must maintain a high suspicion for Clinicians must maintain a high suspicion for coexisting psychiatric conditionscoexisting psychiatric conditions and should and should provide rational polytherapy when justifiedprovide rational polytherapy when justified

Ongoing research and clinical input on the Ongoing research and clinical input on the criteria for ADHD in adults, including criteria for ADHD in adults, including long-term long-term follow-up studies of DSM-diagnosed follow-up studies of DSM-diagnosed childrenchildren and field trials of symptoms in adults, and field trials of symptoms in adults,

are essential for subsequent revisions of DSM-IV.are essential for subsequent revisions of DSM-IV.

8989


Clinicians can be comfortable treating adults with Clinicians can be comfortable treating adults with childhood histories of ADHD, evidence of current ADHD-childhood histories of ADHD, evidence of current ADHD-related impairment, and a related impairment, and a minimum of fourminimum of four (4), and (4), and not six (6) current hyperactive-impulsive or inattentive not six (6) current hyperactive-impulsive or inattentive symptomssymptoms

Clinicians should make efforts to Clinicians should make efforts to obtain third-party obtain third-party corroborationcorroboration whenever available and should carefully whenever available and should carefully document the evidence of the disorder as justification document the evidence of the disorder as justification for treatmentfor treatment

Clinicians who prescribe medication should Clinicians who prescribe medication should carefully carefully monitor treatment responsemonitor treatment response and the possibility of and the possibility of stimulant abuse and illicit diversionstimulant abuse and illicit diversion

9090

Summary for diagnosis: Adult ADHD Summary for diagnosis: Adult ADHD ((WRAADDS)WRAADDS)

7 primary symptom areas7 primary symptom areas 4 mirror DSM: Attention difficulties, Disorganization, 4 mirror DSM: Attention difficulties, Disorganization,

Hyperactivity/Restlessness, ImpulsivityHyperactivity/Restlessness, Impulsivity 3 cover Emotional Dysregulation: Temper, Affective 3 cover Emotional Dysregulation: Temper, Affective

lability, Emotional over-reactivitylability, Emotional over-reactivity May more accurately describe adult phenotypeMay more accurately describe adult phenotype Requires subject to give retroactive historyRequires subject to give retroactive history Critiques: may exclude inattentive type, excludes Critiques: may exclude inattentive type, excludes

comorbid dx, requires further (other) assessment comorbid dx, requires further (other) assessment of current functioning (?possibly a strength)of current functioning (?possibly a strength)

9191

Summary for diagnosis: Adult ADHD Summary for diagnosis: Adult ADHD ((CAARS)CAARS)

Based on large normative database (n=2000)Based on large normative database (n=2000) For use in ages 18 and overFor use in ages 18 and over Excellent reliability and validityExcellent reliability and validity Self-report and observer (friends, co-workers, family Self-report and observer (friends, co-workers, family

members) reportmembers) report Long version: 66 items/ short version 26 itemsLong version: 66 items/ short version 26 items Focuses more on current symptoms than WRAADDSFocuses more on current symptoms than WRAADDS

ADHD Index and Inconsistency Index provide useful ADHD Index and Inconsistency Index provide useful clinical dataclinical data

Easy to score and obtain (see references)Easy to score and obtain (see references)

9292


Cognitive-Behavioral TreatmentCognitive-Behavioral Treatment Manualized Treatment Manualized Treatment

Safren, et al (2005) Mastering Your Adult ADHD: A Safren, et al (2005) Mastering Your Adult ADHD: A cognitive-behavioral treatment programcognitive-behavioral treatment program

Client workbook: ISBN#0-19-518819-5Client workbook: ISBN#0-19-518819-5Therapist guide: ISBN#0-19-518818-7Therapist guide: ISBN#0-19-518818-7

Patient EmpowermentPatient Empowerment ADD.orgADD.org CHADD.orgCHADD.org

9393

Medications used in Adult ADHD*Medications used in Adult ADHD*

Use pediatric and adolescent guidelines to start Use pediatric and adolescent guidelines to start treatment, as in slides 42-50treatment, as in slides 42-50

Most Adults will tolerate larger doses than Most Adults will tolerate larger doses than typical doses used in pediatricstypical doses used in pediatrics Dosing of Adult ADHD does not typically need to Dosing of Adult ADHD does not typically need to

exceed FDA maximums for pediatric dosing, though exceed FDA maximums for pediatric dosing, though some exceptions existsome exceptions exist

40 mg Amphetamine40 mg Amphetamine60-72 mg Methylphenidate60-72 mg Methylphenidate100 mg Atomoxetine100 mg Atomoxetine

May be more responsive to TCAs than children/teensMay be more responsive to TCAs than children/teens See Wilens article (2004) for Excellent ReviewSee Wilens article (2004) for Excellent Review

9494


Wilens, et al, 2004*

9595

Psychological issues in Psychological issues in pharmacologic management*pharmacologic management*

30-70 % of all pediatric psychiatric prescriptions are not filled or are 30-70 % of all pediatric psychiatric prescriptions are not filled or are taken improperly (Joshi, 2006)taken improperly (Joshi, 2006)

Why is psychological management important?Why is psychological management important? Parent issues:Parent issues:

Ambivalence re: need for meds or having “caused” Ambivalence re: need for meds or having “caused” the illnessthe illness

Inadequate parental surveillance of adherenceInadequate parental surveillance of adherence misunderstanding of doses, serum levels, and onset misunderstanding of doses, serum levels, and onset

of effectsof effects Internet information and misinformationInternet information and misinformation

9696

Psychological issues in Psychological issues in pharmacologic management*pharmacologic management*

All of our actions have meaning to the patient All of our actions have meaning to the patient and familyand familyWhat language do we use to explain the theoretical What language do we use to explain the theoretical

nature of their child’s illness?nature of their child’s illness?Many patients (esp teens) attach meaning to Many patients (esp teens) attach meaning to

the medication itselfthe medication itselfOnce taken, it b/c psychologically incorporated Once taken, it b/c psychologically incorporated

into the patient’s view of himself/herself, and into the patient’s view of himself/herself, and can change their sense of identitycan change their sense of identity

The meaning and significance of a drug can The meaning and significance of a drug can affect the way patients view the drug, the affect the way patients view the drug, the prescriber, and themselves prescriber, and themselves ((Lieberman & Tasman, 2000)Lieberman & Tasman, 2000)

9797

ConclusionsConclusions

Remember that all of our actions Remember that all of our actions have potential meaning to the have potential meaning to the patient, from the pens we write with, patient, from the pens we write with, to the language used to explain to the language used to explain about mental illness, to the way we about mental illness, to the way we offer realistic hope for the futureoffer realistic hope for the future

9898


Which of the listed disorders is the most Which of the listed disorders is the most common co-morbidity with ADHD in common co-morbidity with ADHD in children?children?A-Learning disorders in MathA-Learning disorders in MathB-Learning disorders in expressive languageB-Learning disorders in expressive languageC-Oppositional defiant disorderC-Oppositional defiant disorderD-Separation anxiety disorderD-Separation anxiety disorderE-Gender Identity Disorder of ChildhoodE-Gender Identity Disorder of Childhood

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Question 2Question 2Which of the following adverse events Which of the following adverse events

have been reported with atomoxetine in have been reported with atomoxetine in adults?adults?A-Sexual side effectsA-Sexual side effectsB-Stevens-Johnson syndromeB-Stevens-Johnson syndromeC-BradycardiaC-BradycardiaD-HypotensionD-HypotensionE-None of the aboveE-None of the above

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A diagnosis of ADHD in adults must A diagnosis of ADHD in adults must include?include?A- Retrospective history of ADHD symptoms A- Retrospective history of ADHD symptoms

before the age of 7-12 yearsbefore the age of 7-12 yearsB- History of school failureB- History of school failureC- History of motor vehicle accidentsC- History of motor vehicle accidentsD- History of failed multiple marriagesD- History of failed multiple marriagesE- History of substance abuseE- History of substance abuse

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Which of the following statements about Which of the following statements about bupropion is true?bupropion is true? A-It should not be used in youth with a history of A-It should not be used in youth with a history of

seizure disorder seizure disorder B-It should not be used in youth with a history of B-It should not be used in youth with a history of

eating disordereating disorder C-It can be associated with serum sicknessC-It can be associated with serum sickness D-it has off-label use for ADHDD-it has off-label use for ADHD E-All of the aboveE-All of the above

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Which 2 of the following instruments are Which 2 of the following instruments are useful in diagnosing adult ADHD?useful in diagnosing adult ADHD?A-CAARSA-CAARSB-CARSB-CARSC-BAARSC-BAARSD-WRAADSD-WRAADSE-CARBSE-CARBS

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AnswersAnswers

1-c1-c2-a2-a3-a3-a4-e4-e5-a, d5-a, d

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Resources:Resources:

www.schwablearning.orgwww.schwablearning.org www.chadd.orgwww.chadd.org www.add.orgwww.add.org Parents Helping Parents (Parents Helping Parents (www.php.comwww.php.com)) NAMI (www.nami.org)NAMI (www.nami.org) www.whatmeds.comwww.whatmeds.com www.aacap.orgwww.aacap.org (Amer Acad of Child & Adol (Amer Acad of Child & Adol

Psychiatry: Facts for Families)Psychiatry: Facts for Families) www.parentsmedguide.org (antidepressants)www.parentsmedguide.org (antidepressants)

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ResourcesResources Kaye DL, et al: Kaye DL, et al: Child and Adolescent Mental Health;Child and Adolescent Mental Health; 2003; 2003;

Philadelphia: LippincottPhiladelphia: Lippincott*excellent guide for both medical and non-medical providers, about *excellent guide for both medical and non-medical providers, about

the cost and size of the Harriet Lane Handbook*the cost and size of the Harriet Lane Handbook*

Wilens, Timothy:Wilens, Timothy: Straight Talk about Psychiatric Medications for Straight Talk about Psychiatric Medications for KidsKids, revised edition, Guilford Press, 2004, revised edition, Guilford Press, 2004 *well-written and recently revised; among the best medication resources *well-written and recently revised; among the best medication resources

for parents, teachers, nurses, and therapists*for parents, teachers, nurses, and therapists*

Steiner, Hans (ed.): Steiner, Hans (ed.): Handbook of Mental Health Interventions in Handbook of Mental Health Interventions in Children and Adolescents: An Integrated Developmental Approach, Children and Adolescents: An Integrated Developmental Approach, 2004; SF, Jossey-Bass2004; SF, Jossey-Bass

*excellent evidence-based text for working with children, families, *excellent evidence-based text for working with children, families, & systems*& systems*

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ResourcesResources Connors (CPRS, CAAARS) rating scales may be obtained through Connors (CPRS, CAAARS) rating scales may be obtained through

Multi-Health Systems (along with instructions for scoring): 908 Multi-Health Systems (along with instructions for scoring): 908 Niagara Falls Blvd., North Tonawanda, NY 14120-2060, (800) 456-Niagara Falls Blvd., North Tonawanda, NY 14120-2060, (800) 456-3003.3003.

Wender-Reimherr Adult ADD Scale can be obtained through Wender-Reimherr Adult ADD Scale can be obtained through http://www.add-pediatrics.com/add/wender.htmlhttp://www.add-pediatrics.com/add/wender.html Ref- Ref- Ward MFWard MF, , WenderWender PH PH, , ReimherrReimherr FW FW: The Wender Utah Rating Scale: an : The Wender Utah Rating Scale: an

aid in the retrospective diagnosis of childhood attention deficit aid in the retrospective diagnosis of childhood attention deficit hyperactivity disorder hyperactivity disorder Am J PsychiatryAm J Psychiatry. 1993 Jun;150(6):885-90. . 1993 Jun;150(6):885-90.

Golstein S & Ellison AT: Clinician’s Guide to Adult ADHDGolstein S & Ellison AT: Clinician’s Guide to Adult ADHD, , 2002; 2002; London, Academic PressLondon, Academic Press

Barkley RA: Barkley RA: Attention Deficit Hyperactivity Disorder: A Handbook Attention Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment, 3rd Edfor Diagnosis and Treatment, 3rd Ed. 2007; NY, Guilford. 2007; NY, Guilford

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References:References: Slides 21 and 22 are courtesy of H. Brent Solvason, MD, PhDSlides 21 and 22 are courtesy of H. Brent Solvason, MD, PhD

Stein MT: Attention-Deficit/Hyperactivity Disorder: The Diagnostic Process Stein MT: Attention-Deficit/Hyperactivity Disorder: The Diagnostic Process From Different Perspectives; From Different Perspectives; Pediatrics,Pediatrics, Nov 2004; 114: 1453 - 1457. Nov 2004; 114: 1453 - 1457.

MTA Cooperative GroupMTA Cooperative GroupNational Institute of Mental Health Multimodal Treatment Study of ADHD National Institute of Mental Health Multimodal Treatment Study of ADHD Follow-up: Changes in Effectiveness and Growth After the End of Follow-up: Changes in Effectiveness and Growth After the End of TreatmentTreatment; ; PediatricsPediatrics, Apr 2004; 113: 762 - 769. , Apr 2004; 113: 762 - 769.

Arnold LE: Methylphenidate vs. Amphetamine: A Comparative Review, in: Arnold LE: Methylphenidate vs. Amphetamine: A Comparative Review, in: Greenhill and Osman (Greenhill and Osman (eds) eds) Ritalin, Theory and Practice, Ritalin, Theory and Practice, Liebert, NY, 2000Liebert, NY, 2000

Greenhill, L. L., Pliszka, S. R., Dulcan, M. K., & and the Workgroup on Greenhill, L. L., Pliszka, S. R., Dulcan, M. K., & and the Workgroup on Quality Issues. (2002). Practice Parameter for the Use of Stimulant Quality Issues. (2002). Practice Parameter for the Use of Stimulant Medications in the Treatment of Children, Adolescents and Adults. Medications in the Treatment of Children, Adolescents and Adults. Supplement to Journal of the American Academy of Child and Adolescent Supplement to Journal of the American Academy of Child and Adolescent Psychiatry, 41Psychiatry, 41(2), 26S-49S(2), 26S-49S..

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References:References: Joshi SV, et al: Stimulants, atomoxetine, and other agents used to treat Joshi SV, et al: Stimulants, atomoxetine, and other agents used to treat

ADHD, in: Steiner, ADHD, in: Steiner, Handbook of Mental Health Interventions in Children and Handbook of Mental Health Interventions in Children and Adolescents: An Integrated Developmental Approach, Adolescents: An Integrated Developmental Approach, 2004; SF, Jossey-Bass2004; SF, Jossey-Bass

Joshi SV: Teamwork: The therapeutic alliance in pharmacotherapy with Joshi SV: Teamwork: The therapeutic alliance in pharmacotherapy with children and teenagers, in: Martin A & Bostic J (eds.), children and teenagers, in: Martin A & Bostic J (eds.), Child & Adolescent Child & Adolescent Psychiatry Clinics of North AmericaPsychiatry Clinics of North America, 15 (2006), pp239-262, 15 (2006), pp239-262

Pliszka, S. R., and the Texas Consensus Conference Panel on Medication Pliszka, S. R., and the Texas Consensus Conference Panel on Medication Treatment of Childhood Attention-Deficit/Hyperactivity Disorder. (2000). The Treatment of Childhood Attention-Deficit/Hyperactivity Disorder. (2000). The Texas children's medication algorithm project: Report of the Texas consensus Texas children's medication algorithm project: Report of the Texas consensus conference panel on medication treatment of childhood conference panel on medication treatment of childhood attention-deficit/hyperactivity disorder. Part I,II.attention-deficit/hyperactivity disorder. Part I,II. J Am Acad Child Adolesc J Am Acad Child Adolesc PsychiatryPsychiatry ( (JAACAP) 39,JAACAP) 39, 908-927. 908-927.

Revision and update of the above in Pliszka et al. : Revision and update of the above in Pliszka et al. : JAACAPJAACAP. 2006 . 2006 Jun;45(6):642-57Jun;45(6):642-57

Pliszka SR, and the AACAP Work Grp on Quality Issues: Practice parameter for Pliszka SR, and the AACAP Work Grp on Quality Issues: Practice parameter for the assessment and treatment of children and adolescents with attention-the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. deficit/hyperactivity disorder. J Am Acad Child Adolesc PsychiatryJ Am Acad Child Adolesc Psychiatry. 2007 . 2007 Jul;46(7):894-921Jul;46(7):894-921

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References:References: Schulz KP: Neurobiological models of ADHD: A brief review of the empirical evidence. Schulz KP: Neurobiological models of ADHD: A brief review of the empirical evidence.

CNS Spectrums,CNS Spectrums, 5(6) pp.34-44 June 2000 5(6) pp.34-44 June 2000

Robin AL: Robin AL: ADHD in Adolescents: Diagnosis and TreatmentADHD in Adolescents: Diagnosis and Treatment (1998); NY Guilford Press (1998); NY Guilford Press

Rugino, TA & Samsock T.C.(2003). Modafinil in children with attention-deficit Rugino, TA & Samsock T.C.(2003). Modafinil in children with attention-deficit hyperactivity disorder; hyperactivity disorder; Pediatric NeurologyPediatric Neurology 29 (2), 136-142 29 (2), 136-142

Plizska S: “The Comprehensive Treatment of Attention and its Disorders”, The 9th Plizska S: “The Comprehensive Treatment of Attention and its Disorders”, The 9th Ann Symposium on Developmental Approaches to Psychopathology- Stanford Univ Ann Symposium on Developmental Approaches to Psychopathology- Stanford Univ Med Center, Stanford, CA (April 2006)Med Center, Stanford, CA (April 2006)

Greenhill, LL, et al. A Randomized, Double-Blind, Placebo-Controlled Study of Greenhill, LL, et al. A Randomized, Double-Blind, Placebo-Controlled Study of Modafinil Film-Coated Tablets in Children and Adolescents with Modafinil Film-Coated Tablets in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder, Attention-Deficit/Hyperactivity Disorder, JAACAPJAACAP, 45(5), May 2006, 45(5), May 2006

Biederman, J et al: Efficacy and safety of modafinil film-coated tablets in children and Biederman, J et al: Efficacy and safety of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, flexible-dose study. double-blind, placebo-controlled, flexible-dose study. PediatricsPediatrics. 2005 . 2005 Dec;116(6):e777-84 Dec;116(6):e777-84

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References:References: Heiligenstein E, Conyers LM, Berns AR, Miller MA, Smith MA (1998) : Preliminary Heiligenstein E, Conyers LM, Berns AR, Miller MA, Smith MA (1998) : Preliminary

normative data on DSM-IV attention deficit hyperactivity disorder in college students. normative data on DSM-IV attention deficit hyperactivity disorder in college students. J J Am Coll HealthAm Coll Health; 46:185–188; 46:185–188

Castellanos FX, Lee PP, Sharp W, et al. (2002): Developmental trajectories of brain Castellanos FX, Lee PP, Sharp W, et al. (2002): Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. disorder. JAMAJAMA;288:1740-1748. ;288:1740-1748.

Freeman MP, et al. (2006): Freeman MP, et al. (2006): Omega-3 Fatty Acids: Evidence Basis for Treatment Omega-3 Fatty Acids: Evidence Basis for Treatment and Future Research in Psychiatryand Future Research in Psychiatry. . J Clin Psychiatry 67:12, December

McGough JJ & Barley RA (2004): Diagnostic controversies in adult attention deficit McGough JJ & Barley RA (2004): Diagnostic controversies in adult attention deficit hyperactivity disorder; hyperactivity disorder; American Journal of Psychiatry, American Journal of Psychiatry, 161 (11); 1948-1956161 (11); 1948-1956

Wilens TE, Faraone SV, Biederman J (2004): Attention-Deficit/ Hyperactivity Disorder in Wilens TE, Faraone SV, Biederman J (2004): Attention-Deficit/ Hyperactivity Disorder in Adults ;Adults ; JAMA JAMA, 292(5): 619-623, 292(5): 619-623

Richardson AJ (2004): Long-chain polyunsaturated fatty acids in childhood Richardson AJ (2004): Long-chain polyunsaturated fatty acids in childhood developmental and psychiatric disorders; developmental and psychiatric disorders; Lipids Lipids ;39(12):1215-22. ;39(12):1215-22.

Vaidya CJ, et al: Selective effects of MPH in ADHD: An fMRI study. Vaidya CJ, et al: Selective effects of MPH in ADHD: An fMRI study. Proc Nat Proc Nat Acad SciAcad Sci USA, USA, 95:14494-14499, 199895:14494-14499, 1998

ADHD: Assessment and Treatment across the Lifespan*

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