Supported by an educational grant from Shire.

Addressing Treatment Gaps in Adult Patients with ADHD

Faculty Disclosure

• Dr. Rakesh Jain: Consultant—Addrenex, Allergan, Lilly, Lundbeck, Merck, Otsuka, Pamlab, Pfizer, Shionogi, Shire, Sunovion, Takeda; Speakers Bureau—Addrenex, Allergan, Lilly, Lundbeck, Merck, Otsuka, Pamlab, Pfizer, Shionogi, Shire, Sunovion, Takeda; Research Support—AstraZeneca, Allergan, Lilly, Lundbeck, Otsuka, Pfizer, Shire, Takeda

• Dr. Saundra Jain: Consultant—Lilly, Otsuka, and Pamlab

Disclosure

• The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off-label or investigational use(s) of drugs, products, and/or devices (any use not approved by the US Food and Drug Administration).

• Brand names are included in this presentation for participant clarification purposes only. No product promotion should be inferred.

• Applicable CME staff have no relationships to disclose relating to the subject matter of this activity.

• This activity has been independently reviewed for balance.

ADHD: An Enormously Common and Impairing Disorder

Prevalence 18- to 44-year-olds: 4.4%Percentage of adults with ADHD who received treatmentwithin the previous 12 months: 11%

SUD = substance use disorder.Froehlich TE, et al. Arch Pediatr Adolesc Med. 2007;161(9):857-864. Kessler RC, et al. Am J Psychiatry. 2006;163(4):716-723. Wilens TE, et al. Postgrad Med. 2010;122(5):97-109.

High degree of psychiatric comorbidities, eg, majordepression, anxiety disorders, bipolar disorder, SUD, etc

Impairment in multiple domains (home, social, school,work)

Chronic course~75% persistence from childhood into adolescence~50% persistence from childhood into adulthood

Jim CarreyMichael Phelps

Adam LevineDr. Hallowell

? ?

ADHD Symptom Evolution: Childhood to Adulthood

Polanczyk G, et al. Curr Opin Psychiatry. 2007;20(4):386-392. Adler LA. J Clin Psychiatry. 2004;65 Suppl 3:8-11.

Inattention

Hyperactivity

Impulsivity

Disorganized

Fidgets or squirms in seat

Blurts out answers

Forgetfulness affects work/ home/financial/personal life

Can’t sit still in business meetings, restlessness

Excessive spending

ADHD: Lifetime Symptom Progression

Pliszka S; AACAP Work Group on Quality Issues. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921. Brown TE, et al. Postgrad Med. 2010;122(5):42-51. Spencer TJ, et al. J Pediatr Psychol. 2007;32(6):631-642. Biederman J. Biol Psychiatry. 2005;57(11):1215-1220.

Behavioral disturbanceAcademic difficulties

Peer relationshipsSelf-esteem issues

Behavioral disturbance

Academic difficultiesSelf-esteem issues

Legal issuesSmokingInjuries

Academic failureOccupational difficulties

Self-esteemSubstance abuseInjuries/accidents

Occupational failureSelf-esteemRelationship

problemsInjuries/accidents

School-ageAdolescent AdultPreschoolPreschool

College-age

What’s Different between DSM-IV and DSM-5? The Highlights

• Age of onset (symptoms)

– DSM-IV: Some symptoms that caused impairment present before age 7; DSM-5: Several symptoms that caused impairment present prior to age 12

• New specifiers

– In partial remission

– Mild, moderate, severe

• Criterion items now include examples specific to adult presentation highlighting lifespan (eg, paying bills, keeping appointments)

• Older adolescents and adults (age ≥17) at least 5 of 9 symptoms required; <17 years old at least 6 of 9 symptoms required

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.

DSM-5 Criteria for ADHD:Inattentive Symptoms (6/9 age <17 years; 5/9 ≥17 years)

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.Arlington, VA: American Psychiatric Association; 2013.

Have difficulty sustaining attention

Inattentive Symptoms/

Patients Often:

Do not seem to listen

Do not follow through on instructions

Have difficulty organizing tasks or

activities

Avoid tasks requiring sustained mental effort

Lose things necessary for tasks

Are easily distracted

Are forgetful in daily activities

Fail to give close attention to details

DSM-5 Criteria for ADHD: Hyperactive/Impulsive Symptoms (6/9 age <17 years; 5/9 ≥17 years)

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.

Interrupt or intrudeon others

Leave seat in classroom inappropriately

Hyperactive/Impulsive Symptoms/

Patients Often:

Run about or climb excessively (or internal restlessness)

Have difficulty playing quietly

Are “on the go” or acts as if “driven by a motor”

Talk excessively

Blurt out answers before questions are completed

Are easily distracted

Have difficultyawaiting turn

Fidget with hands or feet or squirms in seat

Adult ADHD “Ring of Fire”NCS-R: Psychiatric Comorbidities

Odds Ratio (95% CI). *P < .05.GAD = generalized anxiety disorder; NCS-R = National Comorbidity Survey Replication; OCD = obsessive-compulsive disorder; PTSD = posttraumatic stress disorder.Kessler RC, et al. Am J Psychiatry. 2006;163(4):716-723.

Major Depression

2.7*

BipolarDisorder

7.4*

Adult ADHD Comorbidities

Any Substance

Use Disorder

3.0*

OCD1.5

Specific Phobias

2.8*

Social Phobias

4.9*

Panic Disorder

3.0*

PTSD3.9*

GAD3.2*

Impairment is Significant with Undiagnosed ADHD

Able SL, et al. Psychol Med. 2007;37(1):97-107.

0%

5%

10%

15%

20%

25%

30%

35%

Post-CollegeDegree

Unemployed 1 Traffic Citation(past 5 yrs)

ProblemDrinking

Un

dia

gn

ose

d A

DH

D

Non-ADHD Controls (n = 199)

Undiagnosed ADHD (n = 752)

P < .001

P < .01

P < .05

P < .05

ADHD and SUD: Increased Risks across the Board

P ≤ .001. Calculated from multilevel logistic regression adjusted for sex, age, and education and controlled for the random effect of twins. Capusan AJ, et al. J Atten Disord. 2016;[Epub ahead of print].

Population-based sample of Swedish adult twins (N = 18,167)

Associations of ADHD Symptoms with SUD (Adjusted for Sex, Age, and Education and Controlled for the Random Effect of Twins) Compared with Controls/Twins with No ADHD Symptoms

Substance Abuse All Twins, n (%) ADHD ORAlcohol

Alcohol abuse 543 / 17,940 (3.06) 1.88Alcohol dependence 1070 / 17,734 (6.03) 3.58

DrugsStimulants 688 / 17,779 (3.87) 2.45Opiates 1912 / 17,779 (10.75) 1.97Cannabis 2751 / 17,779 (15.47) 2.19Illicit drug use 2940 / 17,779 (16.54) 2.27Poly-substance use 1425 / 17,779 (8.02) 2.54Poly-substance use including alcohol 1704 / 18,027 (9.42) 2.78

Nicotine (smoke and/or “snus”)Regular nicotine use 3115 / 18,167 (17.15) 1.33

ADHD Sxs and subtypes are associated withincreased risks for all SUD outcomes; no differencebetween ADHD subtypes, no substance preference,and no sex differences for the comorbidity

Indirect effect 1 = a1b1 ADHD symptoms Maladaptive schemata Well-being

Indirect effect 2 = a1d21b2 ADHD symptoms Maladaptive schemata Perceived stress Well-being

Indirect effect 3 = a2b2 ADHD symptoms Perceived stress Well-being

Direct effect of ADHD symptoms on well-being = c’

Do Adults with ADHD Experience Just a Cluster of Symptoms, or are There Elements of

Shame, Failure, Loss of Well-Being Involved Too?

Study of 204 adults with ADHD, 52 men, 152 women

Noteworthy Points1. Adults with ADHD have considerable shame, guilt, perceived stress, maladaptive schemata, lowered

sense of well-being2. When treating adults with ADHD, symptom reduction AND addressing these various elements is

critical

Well-Being

MaladaptiveSchemata

c’ = .054*

d21 = .043***

b1 = .019a2 = .062***b2 = .709***a1 = .975***

ADHDSymptoms

PerceivedStress

N = 204; *P < .05, **P < .01, ***P < .001

Miklósi M, et al. J Nerv Ment Dis. 2016;[Epub ahead of print].

The 24-Hour Day of a Typical Adult and Why the Adult with ADHD Needs Longer than 8- to 12-Hour Coverage of Symptoms / Day

Organize kids for school

Adult ADHD:Screening Tools

Distractibility: A Shared Symptom of Multiple Psychiatric Conditions

Task Force on DSM-IV. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Textbook Revision). Arlington, VA; American Psychiatric Association: 2000.

Distractibility

Depressive Disorders

BipolarDisorders

AnxietyDisorders

ADHD

Psychotic Disorders

SUDs

ASRS-VI.I

Kessler RC, et al. Psychol Med. 2005;35(2):245-256.

How to UsePatients simply check 1of the 5 boxes inresponse to each of the6 questions.

ASRS-VI.I

Kessler RC, et al. Psychol Med. 2005;35(2):245-256.

How to ScoreIf ≥4 marks appear in the darkly shaded boxes within the questionnaire, the patient has symptoms highly consistent with ADHD in adults.

ADHD-RS

How to UseThe ADHD Rating Scale-IV obtainsparent ratings regarding the frequencyof each ADHD symptom based onDSM-IV criteria. Parents are asked todetermine symptomatic frequency thatdescribes the child’s home behaviorover the previous 6 months.

The ADHD Rating Scale-IV iscompleted independently by the parentand scored by a clinician. The scaleconsists of 2 subscales: inattention (9items) and hyperactivity-impulsivity (9items). If ≥3 items are skipped, theclinician should use extreme caution ininterpreting the scale. Results from thisrating scale alone should not be usedto make a diagnosis.

Adult ADHD:Nonpharmacologic Options

ADHD RS-Inv

Time Treatment Mean n P

Baseline CBT+DEX 33.35 23 .77

CBT+PLB 32.68 25

Week 15 CBT+DEX 20.87 23 .21

CBT+PLB 24.96 25

Week 20 CBT+DEX 20.78 23 .39

CBT+PLB 23.56 25

CBT in Adult ADHDIts Potential Role as Augmentation Therapy

CBT = cognitive-behavioral therapy; DEX = dextroamphetamine; PLB = placebo. Weiss M, et al. BMC Psychiatry. 2012;12:30.

23 participants randomized to CBT and DEX vs 25 participantsrandomized to CBT and PLB. Manualized CBT in a series of weeklytelephone conference calls with the principal investigators.

0

5

10

15

20

25

30

35

40

Baseline Week 15 Week 20

AD

HD

RS

-In

v

Time

CBT+DEX

CBT+PLB

Physical Exercise for Adults with ADHDIts Potential Role as Augmentation Therapy

Fritz KM, et al. Med Sci Sports Exerc. 2016;[Epub ahead of print].

Results: In young men reporting elevated symptoms of ADHD, a 20-minutebout of moderate intensity cycle exercise transiently enhances motivation forcognitive tasks, increases feelings of energy and reduces feelings of confusion,fatigue, and depression, but has no effect on the behavioral measures ofattention or hyperactivity employed

Study: 32 young men with unmedicated adult ADHD. Single bout of moderatelyintense, 20 minutes of stationary cycling

Noteworthy Points

1. Physical exercise, even very brief, if done at least at moderate intensity, canpositively impact symptoms that negatively affect adults with ADHD

2. However, physical exercise appears not to impact the core attentionaldifficulties of ADHD. Therefore, it’s best reserved as augmentation therapy

Mindful Meditation in Adult ADHD Its Potential Role as Augmentation Therapy

MAP = mindful awareness practices.Bueno VF, et al. Biomed Res Int. 2015;2015:962857.

Brazilian study of 21 adult ADHD patients and 8 controls underwent 8 weekly MAP sessions.

0

(Hed

ges

g)

0.4

0.2

1.6

1.4

0.6

PA

NA

S-X

-Fa

tig

ue

Affective MeasuresAttentionalMeasures

PA

NA

S-X

-Ser

en

ity

AA

Qo

L-L

ife

Pro

du

ctiv

ity

AA

Qo

L-P

syc

ho

log

ical

Hea

lth

AA

Qo

L-R

elat

ion

sh

ips

AA

Qo

L-T

ota

l Q

ual

ity

of

Lif

e

AN

T-H

it R

T B

lock

Ch

ang

e

CP

T-I

I-C

om

mis

sio

n E

rro

rs

CP

T-I

I-D

etec

tab

ilit

y

PA

NA

S-X

-Att

en

tive

nes

s

PA

NA

S-X

-Sh

yn

ess

PA

NA

S-X

-Po

sit

ive

Aff

ect

PA

NA

S-X

-Fe

ar

PA

NA

S-X

-Sad

nes

s

PA

NA

S-X

-Jo

vial

ity

ST

AI-

An

xiet

y

PA

NA

S-X

-Ne

gat

ive

Aff

ect

BD

I-D

epre

ssio

n

AS

RS

-In

atte

nti

on

AS

RS

-Hy

per

acti

vity

-Im

pu

lsiv

ity

2.0

1.8

1.0

0.8

1.2

PA

NA

S-X

-Sel

f-A

ss

ura

nce

AA

Qo

L-L

ife

Ou

tlo

ok

Noteworthy Points

1. Mindfulness practices, when combined with medication treatment, can be added as an augmentation agent

2. The effects of mindfulness on adults with ADHD cover both core symptoms of ADHD, as well as elements of anxiety, mood, and positive psychiatry

Adult ADHD:Brief Neurobiology Update

Overlapping Monoamine Innervation of Prefrontal Cortex – A Possible Reason for

Comorbidities in Adult ADHD

Robbins TW, et al. Annu Rev Neurosci. 2009;32:267-287.

A B

Examining the Cognition and Emotional Dysregulation Pathways in Adults with ADHD

(Stressed vs Non-Stressed Situations)

DMPFC = dorsal medial prefrontal cortex; DLPFC = dorsal lateral prefrontal cortex; rlPFC = rostral lateral prefrontal cortex; VMPFC = ventral medial prefrontal cortex; NA = noradrenaline; DA = dopamine.Arnsten AF. Nat Rev Neurosci. 2009;10(6):410-422.

Prefrontal Regulation during Alert, Non-Stress Conditions

Amygdala Control during Stress Conditions

ADHD is Associated with Structural Changes in DLPFC and ACC

ACC = anterior cingulate cortex; CGa = anterior cingulate gyrus; NAc = nucleus accumbens. Seidman LJ, et al. Biol Psychiatry. 2006;60(10):1071-1080.

• White matter: red• Gray matter (cortex and nuclei): blue

• NAc: red• DLPFC: blue• CGa: blue

Volume Decrease Volume Increase

MRI study of 24 adults with ADHD and 18 healthy controls

Adult ADHD Brain Brain Volumetric Differences between Those with

Current ADHD, Remitted ADHD, and Controls

Jadidian A, et al. J Neuropsychiatry Clin Neurosci. 2015;27(3):173-178.

Noteworthy Points

1. Children with ADHD start out with thinner cortexes

2. If ADHD remits in adult years, the cortical thinning is less, but still not the same thickness as adults without ADHD

3. The thinnest cortexes are in adults with current ADHD

Adult ADHD BrainBrain Volumetric Differences between Those with

Current ADHD, Remitted ADHD, and Controls

Jadidian A, et al. J Neuropsychiatry Clin Neurosci. 2015;27(3):173-178.

Noteworthy Points

1. Adults with ADHD have notably less connectivity in multiple areas (eg, left putamen, left inferior parietal gyrus, bilateral subgenual cortex), but connectivity is not correlated with symptom severity

2. Persistent adult ADHD have worse connectivity as compared to both controls and remitted ADHD

Adult ADHD:Pharmacologic Options

ADHD: Options

Wilens TE, et al. Postgrad Med. 2010;122(5):97-109.

Pharmacologic Treatment

StimulantsMethylphenidateDexedrineAmphetamine (compounds)

Atomoxetine

Alpha-agonistsGuanfacine XRClonidine XRGuan XR / Clon XR + stimulants

AntidepressantsBupropionTricyclics

ModafinilCombinations

FDA Approved(all in Peds, some in Adults)

FDA Approved

FDA Approved(Peds only)

Not FDA Approved

Pharmacologic Treatments Approved for ADHD

Wilens TE, et al. Postgrad Med. 2010;122(5):97-109. Stevens JR, et al. In: Adler LA, et al (Eds). Attention-Deficit Disorder in Adults and Children. Cambridge University Press: Cambridge, UK; 2015:245-258.

Amphetamine-based Formulations Duration of Effect Peds/Adult

Adderall® (mixed amphetamine salts) 4-6 hours -/-

Adderall XR® (mixed amphetamine salts XR) ~12 hours +/+

Dexedrine® Spansule (dextroamphetamine) 6-8 hours +/-

VyvanseTM (lisdexamfetamine) ~12 hours +/+

Methylphenidate-based Formulations

Concerta® (MPH) ~12 hours +/+

Daytrana® (MPH patch) ~12 hours (worn for 9) +/-

Focalin® (dexMPH capsule) ~5 hours +/-

Focalin® XR (dexMPH XR capsule) 10-12 hours +/+

Metadate® CD (MPH controlled-release capsule) 8-10 hours +/-

Ritalin® (MPH) ~4 hours +/-

Ritalin® LA (MPH XR capsule) 8-10 hours +/-

Quillivant XRTM (MPH XR liquid) ~12 hours +/-

Nonstimulants

Strattera® (atomoxetine) 8-24 hours +/+

Intuniv® (guanfacine XR) ~12 hours +/-

Kapvay® (clonidine XR) ~12 hours +/-

Recent FDA Approvals in ADHD

• Aptensio-XR® (MPH extended-release capsules): approved for ages ≥6 (no adult studies available)

• Evekeo® (amphetamine sulphate): 5 and 10 mg tablets

• Adzenys XR-ODT™ (amphetamine extended-release orally disintegrating tablet)

• Several other new options for treatment of ADHD thought to be arriving soon

US Food and Drug Administration. www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.

Atomoxetine in Adult ADHD Results from a Long-Term Study

(with evening measures of ADHD symptom prevalence)

*P ˂ .05, **P ˂ .01, ***P ˂ .001.ATX = atomoxetine; AISRS = Adult ADHD Investigator Symptom Rating Scale; CAARS-Inv = Conners’ Adult ADHD Rating Scale–Investigator Administered–Screening Version; PLA = placebo.Adler LA, et al. J Clin Psychopharmacol. 2009;29(1):44-50.

Most common side effects were nausea, dry mouth, fatigue, decreased appetite, urinary hesitation, and erectile dysfunction

Randomized, multicenter, double-blind, placebo-controlled, 26-week study

Atomoxetine

Placebo

-12

0

-20

Imp

rove

men

t

-8

-4

-14

-18

AISRS Total ScoreWeek

146 2624

ATX n

PLA n

242

246

Mea

n C

han

ge

fro

m B

ase

lin

e

0 8 22204 18122 1610

-16

-2

-10

-6

242

246

222

231

210

225

191

197

162

179

139

153

101

115

Atomoxetine

Placebo

-6

0

-10

Imp

rove

men

t

-4

-2

-7

-9

CAARS-Inv: SV Evening Total ScoreWeek

146 22

ATX n

PLA n

242

246

Mea

n C

han

ge

fro

m B

ase

lin

e

0 8 204 18122 1610

-8

-1

-5

-3

242

246

222

231

210

225

191

197

162

179

136

153

**

***

***

***** *

**

***

*****

**

OROS MPH in Adult ADHDAnother Effective and Generally Well-Tolerated Treatment Option

Most common side effects were anorexia, dry mouth, gastrointestinal problems, tension/jitteriness, insomnia, cardiovascular complaints, depression, anxiety, and dizziness

Randomized, multicenter,

double-blind, placebo-controlled,

with 72 participants

randomized to OROS MPH and 77

to placebo

40

0

AIS

RS

Sc

ore

30

35

25

15

OROS-MPH mg/dayPlacebo mg/day

81.3 ± 31.094.9 ± 25.5

Week (LOCF)0 31 5 62 4

36.036.0

72.6 ± 26.582.2 ± 22.4

77.9 ± 29.692.2 ± 23.8

80.9 ± 31.896.8 ± 25.9

58.7 ± 17.866.3 ± 12.8

5OROS-MPH

Placebo

OROS-MPH mg/kgPlacebo mg/kg

0.98 ± 0.311.15 ± 0.20

0.47 ± 0.140.47 ± 0.14

0.89 ± 0.291.01 ± 0.20

0.96 ± 0.301.12 ± 0.20

0.99 ± 0.321.17 ± 0.18

0.73 ± 0.240.83 ± 0.23

20

10

P = .04*

OROS = osmotic release oral system.Biederman J, et al. Biol Psychiatry. 2006;59(9):829-835.

P = .03 P = .001 P < .001

d-MPH-ER in Adult ADHD Another Effective and Generally Well-Tolerated Treatment Option

d-MPH-ER = extended-release dexmethylphenidate.Spencer TJ, et al. Biol Psychiatry. 2007;61(12):1380-1387.

Most common side effects were headache, decreased appetite, insomnia, dry mouth, and jitteriness

Randomized, multicenter, double-blind, placebo-

controlled, with 168 participants randomized to

d-MPH-ER and 53 to placebo

Baseline

Final Visit

50

25

DS

M-I

V A

DH

D-R

ST

ota

l Sco

re

0d-MPH-ER

20 mgn = 57

d-MPH-ER30 mgn = 54

40

10

Placebo

n = 53

30

45

15

20

35

5

d-MPH-ER40 mgn = 54

P = .006 P = .012 P < .001

35

25

DS

M-I

V A

DH

D-R

SIn

atte

nti

ve S

ub

scal

e S

core

0d-MPH-ER

20 mgn = 57

d-MPH-ER30 mgn = 54

10

Placebo

n = 53

30

15

20

5

d-MPH-ER40 mgn = 54

P = .021 P = .011 P < .001

25

0d-MPH-ER

20 mgn = 57

d-MPH-ER30 mgn = 54

10

Placebo

n = 53

15

20

5

d-MPH-ER40 mgn = 54

P = .005P = .037 P < .001

DS

M-I

V A

DH

D-R

SH

yper

acti

ve/Im

pu

lsiv

eS

ub

scal

e S

core

Triple-Bead Formulations of MASA Potential New Treatment Option for Adult ADHD

*P < .0001 vs placebo; †P = .01 vs placebo; ‡P = .003 vs placebo.AIM = Adult ADHD Impact Module; MAS = mixed amphetamine salts.Spencer TJ, et al. J Clin Psychiatry. 2008;69(11):1766-1775.

Most common side effects were insomnia, dry mouth, decreased appetite, headache, and decreased weight

7-week, Phase 3, randomized, double-blind, placebo-controlled, dose optimization study of triple-bead MAS in adults with ADHD (137 randomized to active treatment, 137

randomized to placebo)

30

5

0Lea

st S

qu

ares

Mea

n C

han

ge

fro

mB

asel

ine

in A

IM-A

Su

bsc

ale

Sco

re

25

15

Living withADHD

10

20

Gre

ater

Imp

rove

men

t

DailyInterference

Bothersome-ness/

Concern

Relationships/Communication

Performanceand Daily

Functioning

*

GeneralWell-Being

Placebo (n = 132)

Triple-Bead MAS (n = 136)

*

*

*†

‡

Adult ADHD:Special Issues / Concerns with

Stimulant Use

Differentiating ADHD from Bipolar Disorder in Adults: Overlapping and Non-Overlapping Symptoms

Kitsune GL, et al. J Affect Disord. 2016;192:125-133.

Clinical Implication for the Treatment of Adult ADHDThe distinction between sustained traits and episodic symptoms that reflect a change in the

premorbid mental state are best at discriminating ADHD from bipolar disorder in adults

King’s College, Institute of Psychiatry, London Study with total 60 adult women were recruited (20 with ADHD, 20 with bipolar disorder, and 20 controls)

1.5

-1.5Std

Mea

n S

core

s (+

/-S

tdE

rr)

-1.0

0

1.0

BAARS-IVSelf-Report

ADHD BD Control

-0.5

0.5

Ch

an

ge

(la

st 4

8h)

BAARS-IVInformant DIVA ASRM DI CNS-LSALSYMRS

No

. Sym

Pa

st

No

. Sym

Pre

s

To

tal

To

tal

An

xDep

Ela

Dep

An

ger

La

st M

on

th

La

st 5

Yea

rs

To

tal

To

tal

Imp

air

men

t

To

tal

Ina

tt

Hyp

-Im

p

Ina

tt

Hyp

-Im

p

Imp

air

men

t

Ina

tt

Hyp

-Im

p

ADHD Symptoms Mania and Dep Symptoms Emotional Lability

Cognitive and Executive System Dysfunction in ADHDWhat are the Impairments?

(and what this means to clinical decision-making)

Salomone S, et al. J Atten Disord. 2016;[Epub ahead of print].

University College of Dublin Study of 51 adults diagnosed with combined ADHD compared with 28 adult controls

Results: ADHD individuals have the following Executive Function Impairments:

1. Divided Attention (P = .04)

2. Sustained Attention – higher number of omissions (P = .001) AND highernumber of commission errors (P = .005)

3. Executive Function Test Hotel task is comprised of 5 distinct activities thatwould plausibly be completed in the course of running a hotel (ie, checkingguests’ bills, proofreading a leaflet on the hotel’s facilities, sorting money,etc). Results: Significantly lower number of attempted tasks (P = .004)

Clinical Implication for the Treatment of Adult ADHDAttentional Problems and Executive Dysfunction are prominent issues and therefore

coverage of symptoms for maximum number of hours/day is a clinical necessity

With Stimulants – FDA Package Insert Directs Clinicians to Exercise the Following Care

US Food and Drug Administration. www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.

Adult ADHD and Car Accidents: What is Known about the Disorder’s Impact,

and Its Treatment’s Impact on Outcomes

Chang Z, et al. JAMA Psychiatry. 2014;71(3):319-325.

Relevant Points

- Males with ADHD had a 1.47 hazard ratio of serious car accidents

- Females had a hazard ratio of 1.45 of serious car accidents

- In males, taking medications for ADHD lead to a 58% risk reduction (infemales it was statistically insignificant)

Sample: 54 incarcerated males (Mean age = 42)

Dose: Start dose 18 mg MPH/placebo titrated over a period of 19 days to max dose of 180 mg/day

CBT: Individual CBT once weekly for 12 weeks

Measurements: Change in self-reported ADHD symptoms, urine tox, retention to treatment

Findings: MPH-treated group showed reduced ADHD symptoms (P = .011), significantly higher proportion of negative urine screens (P = .047), and better retention (P = .032)

MPH for ADHD and Drug Relapse in Criminal Offenders with Substance Dependence:

A 24-Week Randomized Placebo-Controlled Trial

Konstenius M, et al. Addiction. 2014;109(3):440-449.

Placebo

MPH

25

40

20

10CA

AR

S-S

co

re

35

30

Weeks

16 24

15

0123 20

Change in self-rated ADHD symptoms(95% CI: -13.78 to -1.91, P = .011)

81 42Base-line

5

ADHD Medications are Not Associated with Adverse Cardiovascular Outcomes in Adults

Habel LA, et al. JAMA. 2011;306(24):2673-2683.

Relevant Point: Stimulant use in this study was not associated with anincreased risk of serious cardiovascular events

Potential and Common Unmet Needs in Adult ADHD

Potency of intervention not sufficient

In Conclusion: What is an Optimum Response to Treatment in Adults with ADHD?

Attention

Hyper-activity

Impulsive

Behavior

Emotional

Optimum would be early, full, and sustained control over ALL symptoms of ADHD, for AS MANY hours in the day as

possible (with great tolerability, of course!)