/
Recent Updates in ADHD: Recent Updates in ADHD:

Recent Updates in ADHD: - PowerPoint Presentation

WickedlyCool
WickedlyCool . @WickedlyCool
Follow
347 views
Uploaded On 2022-07-28

Recent Updates in ADHD: - PPT Presentation

Optimizing Outcomes in a Digital World Please feel free to use update and share some or all of these slides in your noncommercial presentations to colleagues or patients When using our slides please retain the source attribution ID: 929922

methylphenidate adhd amphetamine children adhd methylphenidate children amphetamine adults adult treatment psychiatry placebo viloxazine tablet baseline acting symptoms 100

Share:

Link:

Embed:

Download Presentation from below link

Download Presentation The PPT/PDF document "Recent Updates in ADHD:" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.


Presentation Transcript

Slide1

Recent Updates in ADHD:

Optimizing Outcomes in a Digital World

Slide2

Please feel free to use, update and share some or all of these slides in your noncommercial presentations to colleagues or patients

When using our slides, please retain the source attribution:These slides may not be published, posted online, or used in commercial presentations without permission. Please contact pce@practicingclinicians.com for details

About These Slides

2

Slide credit: practicingclinicians.com:

Slide3

Faculty

Greg W. Mattingly, MDJune 11; October 8Associate Clinical Professor, Washington University School of MedicinePresident,

Midwest Research GroupPresident Elect, American Professional Society for ADHD and Related Disorders (APSARD)

St Louis, Missouri Joel L. Young, MD

May 14; September 10; November 5Medical Director, Rochester Center for Behavioral MedicineRochester Hills, Michigan

Clinical Associate Professor of Psychiatry

Wayne State University School of Medicine

Detroit, Michigan

3

Slide4

Faculty Disclosures

The faculty reported the following relevant financial relationships or relationships to products or devices they have with ineligible companies related to the content of this educational activity:Greg W. Mattingly, MD, has disclosed that he serves as a speaker for AbbVie, Alkermes, Corium, Eisai, Intracellular, Ironshore, Janssen, Lundbeck, Neurocrine,

Noven, Otsuka, Sunovion, Supernus, Takeda, and Trispharma; has received consulting fees from AbbVie, Acadia, Alkermes, Axsome

, Corium, Eisai, Ironshore, Intracellular, Janssen, Lundbeck, Neos, Neurocrine, Noven, Otsuka, Redax, Roche, Rhodes, Sage, Sirona, Sunovion, Supernus, Takeda, Teva, and

Trispharma; and funds for research support from AbbVie, Acadia, Alkermes, Akili, Axsome, Boehringer, Emalex, Idorsia, Janssen, Karuna, Lumos Labs, Medgenics, NLS-1 Pharma AG, Redax, Relmada, Roche, Sage, Sirtsei

, Sunovion, Supernus, Takeda, and Teva.

Joel L. Young, MD,

has disclosed that he has received consulting fees for Alkermes, Corium, Ironshore, Janssen, Noven, Otsuka, and Supernus and funds for research support from Janssen and Otsuka.

4

Slide5

Learning Objectives

At the conclusion of this activity, learners should be able to:Interpret the impact of screen time and social media on processing speed and ADHD symptoms throughout the lifespanDiscuss the impact of unrecognized or untreated ADHD on mortality rates, school performance, job performance, and impact on daily social functionAssess strategies and options to optimize ADHD care within your practice

5

Slide6

Life is a journey

you are never

quite sure what is next

Slide7

Developmental Phases

Child

Teens

Young Adult

Older Adult

More

Less

Clinical presentation of ADHD changes across development and is related to interplay among environmental demands, available external supports, and typical symptom trajectories

Goodman

et al.

J Clin Psychiatry. 2012;73:192

.

Environmental Demands

7

Slide8

Developmental Phases

External Supports

Goodman

et al.

J Clin Psychiatry. 2012;73:192

.

Child

Teens

Young Adult

Older Adult

Environmental Demands

More

Less

Clinical presentation of ADHD changes across development and is related to interplay among environmental demands, available external supports, and typical symptom trajectories

8

Slide9

Developmental Phases

Hyperactivity

External Supports

Child

Teens

Young Adult

Older Adult

Environmental Demands

More

Less

Clinical presentation of ADHD changes across development and is related to interplay among environmental demands, available external supports, and typical symptom trajectories

Goodman

et al.

J Clin Psychiatry. 2012;73:192

.

9

Slide10

Developmental Phases

Inattention

Hyperactivity

External Supports

Child

Teens

Young Adult

Older Adult

Environmental Demands

More

Less

Clinical presentation of ADHD changes across development and is related to interplay among environmental demands, available external supports, and typical symptom trajectories

Goodman

et al.

J Clin Psychiatry. 2012;73:192

.

10

Slide11

Developmental Phases

Goodman

et al.

J Clin Psychiatry. 2012;73:192

.

Inattention

Hyperactivity

External Supports

Child

Teens

Young Adult

Older Adult

Environmental Demands

More

Less

Clinical presentation of ADHD changes across development and is related to interplay among environmental demands, available external supports, and typical symptom trajectories

11

Slide12

Developmental Phases

Goodman

et al.

J Clin Psychiatry. 2012;73:192

.

Inattention

Hyperactivity

External Supports

Child

Teens

Young Adult

Older Adult

Environmental Demands

More

Less

Clinical presentation of ADHD changes across development and is related to interplay among environmental demands, available external supports, and typical symptom trajectories

12

Slide13

Adult-Onset or Adult Diagnosis of ADHD

Risk factors for adult diagnosis of ADHD:Female sexHigher IQMore years of education

Breda

et al.

Br J Psychiatry. 2021;218:43. Horrigan

et al.

AACAP. 2000

.

Full-Scale IQ

Age at Initial Diagnosis (Yr)

150

140

130

120

110

100

90

80

70

50

0

10

20

30

40

Age at Initial Diagnosis vs Full-Scale IQ

(314.00)

13

KEY TAKE HOME:

IQ can compensate for the impairments of ADHD and forestall diagnosis

Slide14

Impact of Social Media on ADHD

Ra et al. JAMA. 2018;320:255

.

Estimated mean prevalence of ADHD symptoms across follow-ups by baseline modern digital media use frequency index

derived from the primary unadjusted repeated measures logistic regression model among baseline ADHD symptom–negative students

Mean ADHD Symptom Prevalence Across Follow-ups, % (+95% CI)

Baseline No. of Digital Media Activities Used at a High Frequency Rate

0

2

4

6

8

10

12

14

16

18

20

0

n = 495

1

n = 337

2

n = 313

3

n = 321

4

n = 268

5

n = 243

6

n = 167

7

n = 114

8

n = 91

9

n = 66

10

n = 54

11

n = 34

12

n = 17

13

n = 16

14

n = 51

KEY TAKE HOME:

In the top decile of social media use, 14% of high school juniors

now meet criteria for ADHD

14

Slide15

What About Memory and Aging?

Schaie et al. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2004;11:304

.

Mean T-Scores

Age (Yr)

35

40

45

50

55

25

32

39

46

53

60

67

74

81

88

Inductive reasoning

Spatial orientation

Perceptual speed

Numeric ability

Verbal ability

Verbal memory

15

Slide16

Risk of Cognitive Impairment

Odds Ratio (95% CI)Digit Symbol Substitution Test

Relative Risk for Impairment

Impact of Television and Exercise After 25 Yr

Hoang et al. JAMA Psychiatry. 2016;73:73

.

Most active

Intermediate

Least active

1

16

Slide17

MTA Study Followed Into Adulthood

9.1%

of demonstrated recovery (sustained remission)

10.8%

demonstrated stable ADHD persistence

63.8%

had fluctuating periods of remission and recurrence over time

KEY TAKE HOME:

90% continued to

have ADHD symptoms into adulthood

Sibley et al. Am J Psychiatry. 2022;179:142.

Total Sample (%)

Years After Baseline

100

90

80

70

60

50

40

30

20

10

0

16

0

2

3

6

8

10

12

14

DSM ADHD (persistent)

Partially remitted

Fully remitted

Recovered

Stable partial remission

Stable persistence

Fluctuating status

17

Slide18

Common Myths of ADHD

Only in boysTwice as common in boys but equally prevalent in adultsAnd girls are more likely to be missedYou eventually grow out of itRecent data shows that only 10% of children diagnosed with ADHD do not have ADHD issues as adultsHyperactivity is the outward marker

Two thirds of boys have hyperactivity, but the majority of girls do notTry a test dose of a stimulant to see if you focus betterMost individuals feel that they focus better with a stimulant, but over time they quickly build a tolerance and need higher and higher doses

18

Slide19

Suicide, Homicide, and Unintentional Injury

Outcome or Subgroup

Adjusted Model 1

HR (95% CI)

P

Value

All cause

Total

1.32 (1.22-1.43)

<.001

Male

1.26 (1.15-1.39)

<.001

Female

1.52 (1.28-1.79)

<.001

Suicide

Total

2.71 (2.16-3.4)

<.001

Male

2.48 (1.88-3.28)

<.001

Female

3.18 (2.13-4.75)

<.001

Unintentional injury

Total

1.32 (1.12-1.54)

.001

Male

1.29 (1.09-1.53)

.003

Female

1.44 (0.92-2.26)

.11

Homicide

Total

2.10 (1.14-3.84)

.02

Male

1.93 (0.98-3.79)

.06

Female

3.06 (0.77-12.17)

.11

Natural causes

Total

1.14 (1.02-1.27)

.02

Male

1.09 (0.96-1.24)

.17

Female

1.28 (1.04-1.58)

.02

Chen et al. JAMA Netw Open. 2019;2:e198714

.

19

Slide20

Comorbidities in College-Age Adults:

Important Considerations in Our Differential N = 443 (214 men and 229 women), aged 18-22 yr (Median = 18.2 yr),

recruited from 9 colleges involved in a large-scale, multisite longitudinal investigation

College students with ADHD:

55% had ≥1 and 31.8% had ≥

2 comorbid conditions

College students without ADHD:

11.2% and 4.0%, respectively

Comorbid

and Non-ADHD Disorders by Group

Disorder

ADHD, %

Comparison, %

P

OR

Depressive

32.3

5.4

<.001

8.4

Anxiety

28.63.6<.00110.8

GAD15.51.8<.001

10.0Trauma and stressor7.30.9.0018.7

Learning disorder

10.0

0.4<.00124.7

Anastopoulos et al. J Clin Child Adolesc Psychol. 2018;47:236.20

Slide21

Psychiatric Comorbidities Increase the

Risk of Premature Mortality in Adults With ADHD

Outcome or Subgroup

Deaths, n

Person-Yr

Mortality Rate per 10,000 Person-Yr

HR (95% CI)

Model 1

Overall

3821

16,206,949

2.36

NA

ADHD only

39

102,989

3.79

1.56 (1.11-2.18)

ADHD plus 1 comorbidity

73

57,575

12.68

4.21 (3.27-5.42)

ADHD plus 2 comorbidities9029,952

30.058.57 (6.73-10.92)ADHD plus 3 comorbidities

7314,14651.6015.69 (12.08-20.37)ADHD plus ≥4 comorbidities94

10,334

90.96

29.29 (22.77-37.66)None of the above345215,991,9532.161 [Reference]

Sun et al. JAMA Psychiatry. 2019;76:1141

.21

Slide22

Polygenic Risk for ADHD and Associated Traits

(A) target phenotypes and (B) items on the neuroticism scale. Values displayed next to each bar represent

the

P

value for significance for the most predictive models.

BMI

General cognitive ability

Alcohol intake

Risk taking

Neuroticism

Tobacco use

Depression

Alcohol dependency

Anxiety disorder

Bipolar disorder

Schizophrenia

Phenotype (Best Fit)

Mood swings

Fed-up feelings

Miserableness

Irritability

Tense/high strung

Guilty feelings

Sensitivity/hurt feelings

Suffer from nerves

Worry after embarrassment

Nervous feeling

Worrier/anxious feelings

Phenotype (Best Fit)

Loneliness/isolation

6.7 x 10

-44

6.9 x 10

-42

4.5 x 10

-34

5.4 x 10

-29

3 x 10

-18

3.5 x 10

-13

3.4 x 10

-12

6 x 10

-12

0.002

0.009

0.042

0.267

0

0.0005

0.0010

0.0015

0.0020

0.0025

Variance Explained: R

2

0

Variance Explained: R

2

0.002

0.004

0.162

0.007

2.9 x 10

-4

4.5 x 10

-6

2.2 x 10

-13

4.2 x 10

-21

2.2 x 10

-24

9.3 x 10

-25

8.1 x 10

-29

4.5 x 10

-36

4.5 x 10

-129

-log

10

model

P

value

40

30

20

10

-log

10

model

P

value

40

30

20

10

Du

Rietz

et al.

Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:635.

A

B

22

Slide23

ADHD Treatment Reduces the Risk of Suicidality

in Patients With Comorbid ADHD and BD/SZDWithin 6 mo after treatment initiation, SA and NSSI events decreased significantly in terms of: Number of patients having SA/NSSI (P = .013)Numbers of SA/NSSI events experienced (

P = .004)Hospitalizations decreased from 31 to 19 (P

= .029)OR: 0.63 with stimulant treatment

ADHD and comorbid BD/SZD

19%

of patients (206)

met the criteria for

KEY TAKE HOME:

Appropriate ADHD treatment may decrease SA/NSSI in patients with BD/SZD

who have ADHD

Of 1564

patients with

BD/SZD:

Öhlund et al. Ther Adv Psychopharmacol. 2020;10:2045125320947502

.

23

Slide24

Motor Vehicle Trauma and ADHD Medication Usage

Chang et al. JAMA Psychiatry. 2017;74:597

.

Reduction in Trauma Rates (%)

27

34

49

60

50

40

30

20

10

0

Women: 2-Yr Follow-up

Men: 2-Yr

Follow-up

Motorcyclists

During Mo Taking Medication

Reduction in MVA Trauma Rates

While Taking ADHD Medications

24

Slide25

The Benefits of Treating ADHD

Treatment of adult ADHD with licensed medications may lead to benefits across a range of outcomes—including core symptoms, executive function, and quality of life—within a relatively short period of timeIn a systematic analysis of 48 studies and 76 outcome measures in patients with ADHD, treatment of ADHD was associated with benefit in numerous areas

Treatment benefit by outcome group in treated patients with ADHD vs untreated ADHD

25

Collective clinical opinion of Steering Group members. Shaw et al. BMC Med 2012;10:99.

Outcome

25

Slide26

Whom Should You Screen?

Patients presenting with:Family history or children with ADHD Treatment-resistant MDD, bipolar disorder, or anxiety disordersDrug abuse or drug dependence Poor school performance as a child (not reaching potential) Poor occupational performance as an adult (not reaching potential) Motor vehicle issuesForgetfulness (missed appointments, trouble with adherence to medications)

Screening: PDF

P

rocrastinationD

istractibility

F

orgetfulness

Canadian ADHD Resource Alliance (CADDRA). 4th Edition. 2018. Bond et al. Ann Clin Psychiatry. 2012;24:23.

Lam et al. J Affect Disord. 2009;117(suppl 1):S26. Mattingly et al. CNS Spectr. 2016;21:45.

26

Slide27

Reduction in ADHD-RS

Reduction in Functional Impairment

ADHD Diagnosis

Average ADHD-RS: 30-40

ADHD patient

before diagnosis

ADHD-RS: 0-54 (

18 symptoms rated 0-3

)

Standard reduction

of symptoms

Standard Reduction

Average ADHD-RS: 20-30

Optimal Improvement Average ADHD-RS: <18

Goal:

Minimal functional impairment

Optimizing ADHD Symptom Reduction

Can Minimize Functional Impairment

Mattingly et al. CNS Spectr. 2016;21:45.

27

Slide28

16%

Responded

better to MPH than AMPH

28%

Responded

better to AMPH

than MPH

Methylphenidate vs Amphetamine?

41%

Responded to

both AMPH and MPH (“double responders”)

13%

Did not respond to either medication

Most patients (n = 152/174; 87%) responded to

MPH and/or AMPH

In Pediatric Studies

Mattingly et al. Postgrad Med. 2017;129:657. Arnold et al. J Atten Disord. 2000;3:200.

28

Slide29

Network Meta-analysis: Results of ADHD Treatment

Mean Change in ADHD Symptoms, Rated by Healthcare Professionals

Favors Placebo

Favors Drug

Favors Placebo

Favors Drug

Children and Adolescents

Adults

SMD (95% CI)

SMD (95% CI)

Amphetamines

-1.02 (-1.19 to -0.85)

-0.79 (-0.99 to -0.58)

Atomoxetine

-0.56 (-0.66 to -0.45)

-0.45 (-0.58 to -0.32)

Bupropion

-0.96 (-1.69 to -0.22)

-0.46 (-0.85 to -0.07)

Clonidine

-0.71 (-1.17 to -0.24)

Guanfacine

-0.67 (-0.85 to -0.50)

Methylphenidate

-0.78 (-0.93 to -0.62)

-0.49 (-0.64 to -0.35)

Modafinil

-0.62 (-0.84 to -0.41)

0.16 (-0.28 to 0.59)

0.5

-1

-0.5

0

Favors Placebo

Favors Drug

0.5

-1

-0.5

0

Favors Placebo

Favors Drug

Cortese et al. Lancet Psychiatry. 2018;5:727.

29

Slide30

Transition from Methylphenidate to

Amphetamine Occurs in Adolescence

US Stimulant Prescriptions

Methylphenidate

Amphetamine

IMS NPA Market Dynamics

RETAIL Rx ONLY. Mattingly et al. CNS Spectr. 2016;21:45.

Age (

yr

)

30

Slide31

Currently Approved ADHD Medications Reflect

Limited Distinct Approaches for Adult Patients

Stimulants

Nonstimulants

Atomoxetine

Viloxazine XR

(kids and adults)

ER

α

2 adrenergic agonists

Stimulants

Methylphenidate

Short acting

Short acting

Long acting

(kids and adults)

Amphetamine

Approved

Investigational

Several MoAs under investigation

Long acting

(kids and adults)

adhdmedicationguide.com. accessdata.fda.gov/scripts/cder/daf/. De Sousa et al. Mens Sana Monogr. 2012;10:45. Spencer et al. J Clin Psychiatry. 2002;63:16. Stahl et al. Prim Care Companion J Clin Psychiatry. 2004;6:159. Chang et al. J Experiment Clin Med. 2013;5:210. clinicaltrials.gov/.

31

Slide32

Methylphenidate Preparations

Adapted from Mattingly et al. CNS Spectr. 2021;26:104.

Delivery Mechanism and Formulation

Generic Name

Approved Ages

Doses/d

Onset

Duration

Comments

Short acting

Dexmethylphenidate

tablet

Dexmethylphenidate HCl

Children ≥6 yr

2

NA

6 hr

At least 4 hr between doses

Methylphenidate tablet

Methylphenidate HCl

Children ≥6 yr, adults

2-3

1-2 hr

4 hr

Methylphenidate chewable tablet and liquid

Methylphenidate HClChildren ≥6 yr, adults2-31 hr

4 hr

Chewable tablet: take with 8 oz of water before meals

Oral solution: take 30-45 min before mealsLast dose before 6 PMIntermediate acting

Methylphenidate tabletMethylphenidate HClChildren ≥6 yr, adults1NA

8 hr

Methylphenidate capsule

Methylphenidate HCl

Children 6-15 yr

1

1.5 hr

8-9 hr

May be sprinkled on applesauce

Long acting

Dexmethylphenidate capsule

Dexmethylphenidate HCl

Children ≥6 yr, adults

1

30 min

12 hr

May be sprinkled

Methylphenidate chewable tablet (3 preparations)

Methylphenidate HCl

Children ≥6 yr, adults

1

45 min

8 hr

Methylphenidate chewable tablet

Methylphenidate HCL

Children 6-12 yr

1

30 min to

1 hr

12 hr

May be sprinkled

Methylphenidate chewable tablet

Methylphenidate HCL

Children ≥6 yr, adults

1

1-2 hr

10-12 hr

Methylphenidate liquid

Methylphenidate HCl

Children ≥6 yr, adults

1

45 min

12 hr

Shake bottle vigorously for 10 s before dispensing

Methylphenidate ODT

Methylphenidate HCl

Children ≥6 yr

1

1 hr

12 hr

No crushing or chewing

Allow to disintegrate in saliva before swallowing

Methylphenidate transdermal patch

Methylphenidate

Children ≥6 yr

1

2 hr

12 hr

Wear for ≤9 hr

Methylphenidate capsule

(3 preparations)

Methylphenidate HCl

Children ≥6 yr, adults

1

1 hr

12 hr

May be sprinkled

Methylphenidate capsule

Methylphenidate HCL

Children ≥6 yr, adults

1

1 hr

13-16 hr

May be sprinkled and consumed within 10 min

Methylphenidate capsule

Methylphenidate HCL

Children ≥6 yr, adults

1

8-10 hr

12+ hr

Take in the evening between 6:30 and 9:30 PM for early morning symptom control; may be sprinkled

32

Slide33

Amphetamine Preparations

Adapted from Mattingly et al. CNS Spectr. 2021;26:104.

Delivery Mechanism

and Formulation

Generic Name

Approved Ages

Doses/d

Onset

Duration

Comments

Short acting

Amphetamine tablet

Amphetamine mixed salts

Children ≥3 yr

1-3

1.5 hr

4-6 hr

Elimination half-life 9.77-11 hr for the D-isomer and

11.5-13.8 hr for L-isomer

Dextroamphetamine tablet

(2 preparations)

Dextroamphetamine sulfate

Children 3-16 yr

1-2

NA4-6 hr

Dextroamphetamine tabletDextroamphetamine sulfateChildren 3-16 yr1-3NA

4-6hr

Dextroamphetamine liquid

Dextroamphetamine sulfateChildren 6-16 yr1-2NA6-10 hrPlasma half-life of approximately 12 hr

Methamphetamine tabletMethamphetamine HClChildren ≥6 yr1-2NA

NA

Not readily available

Intermediate acting

Amphetamine tablet and ODT

Racemic amphetamine sulfate

Children ≥3 yr (tablet); Children

6-17 yr (ODT)

1-2

45 min

9.25 hr

Elimination half-life 10.0-11.7 hr

Dextroamphetamine capsule

Dextroamphetamine sulfate

Children 6-16 yr

1-2

NA

6-10 hr

Plasma half-life of approximately 12 hr

Long acting

Amphetamine capsule

(2 preparations)

Amphetamine mixed salts

Children ≥6 yr, adults

1

1.5 hr

10.5-12 hr

May be sprinkled on applesauce

Amphetamine capsule

Amphetamine mixed salts

Children ≥13 yr, adults

1

2 hr

14 hr

May be sprinkled on applesauce

Amphetamine liquid

(2 preparations)

Amphetamine

Children ≥6 yr

1

1 hr

12

Amphetamine liquid

Children ≥6 yr, adults

1

1.5 h

10-12 h

Do not add to food or other liquids

Amphetamine ODT

Amphetamine

Children ≥6 yr, adults

1

1.5 h

10-12 h

Allow tablet to disintegrate in saliva before swallowing

Amphetamine prodrug capsule and chewable tablet

Lisdexamfetamine dimesylate

Children ≥6 yr, adults

1

1.5-2 hr

12-14 hr

Capsule: may be sprinkled in water, orange juice, or yogurt

Chewable tablet: chew thoroughly before swallowing

33

Slide34

Nonstimulant Options

*

Adapted from Mattingly et al. CNS Spectr. 2021

;26:104.

Delivery Mechanism

and Formulation

Generic Name

Approved Ages

Doses

per Day

Onset Effect

Duration of Effect

Comments

Long acting

Norepinephrine transporter reuptake inhibitor capsule

Atomoxetine

Children ≥6 yr, adults

1-2

3-4 wk

NA

Dosed by body weight

α

2

-adrenergic receptor agonist tablet

Clonidine HClChildren ≥6 yr22 wkNAAn antihypertensive agent may be prescribed in addition to a stimulant

Discontinuation must be gradualα2-adrenergic receptor agonist tabletGuanfacineChildren ≥6 yr 1

3 wkUp to 24 hr

per dose

An antihypertensive agent may be prescribed in addition to a stimulantDosed by body weightSerotonin norepinephrine modulating agent capsuleViloxazine HClChildren 6-17 yr11 wk24 hr

34

Slide35

Nonmedical Use of Prescription

Stimulants Among College Students

Butler et al. Front Psychiatry.

2021;12:667118.

*Results based on an online survey conducted in 2016 with 3379 respondents aged 18-26 yr. The current study includes a subsample of

486 respondents who met the inclusion criteria (aged 18-26 yr, currently enrolled in college, and reported prescription stimulant NMU at any time in their lifetime).

Patterns of NMU of Prescription Stimulant Medications*

100

80

60

40

20

0

College Students (%)

Polysubstance

Use

IS Other Than Marijuana

IS Prior to Rx Stimulant

IS and Prescription Stimulant Simultaneously

NMU of Prescription Stimulant Prior to IS

Lifetime

Diagnosis of ADHD

91.4

55.0

43.0

23.6

32.0

43.0

35

Slide36

FDA-Approved Medications With

Clinical Data for Adults With ADHD *Now also includes delayed-release/extended-release methylphenidate, time-release methylphenidate, prodrug methylphenidate, and viloxazine XR.

Medication

Molecule

Hr

Adult Dosing

Atomoxetine

Nonstimulant

24

40-100 mg

Dexmethylphenidate XR

2 beads

Methylphenidate

12*

10-40 mg

OROS methylphenidate

OROS capsule

Methylphenidate

12*

18-72 mg

Mixed amphetamine XR

2 beads

Amphetamine

12

10-20 mg

Lisdexamfetamine

Prodrug

Amphetamine

14

20-70 mg

Mixed amphetamine ER

3 beads

Amphetamine

16

12.5-50 mg

Mattingly et al. CNS Spectr. 2016;21:45.

36

Slide37

What About the New Kids on the Block?

Slide38

Serdexmethylphenidate C-IV/d-Methylphenidate C-II:

A 70/30 Prodrug/d-MPH Combination

70/30 combination:

70% prodrug d-MPH;30% d-MPH

Serdex prodrug is C-IVDoses:

26.1 mg/5.2 mg

39.2 mg/7.8 mg

52.3 mg/10.4 mg

Starting dose is

39.2 mg/7.8 mg

Serdexmethylphenidate/Dexmethylphenidate PI.

Placebo

d-MPH/Serdex

LS Mean SKAMP-Combined Change From Baseline

Hr

0

0.5

1

2

4

8

10

12

13

-12

-10

-8

-6

-4

-2

0

2

4

38

Slide39

Serdex/d-MPH: Long-term Efficacy, 1-Yr Open-Label Study

Childress et al. APSARD 2021. Poster.

Mean ADHD RS-5 Total Score

0

5

10

15

20

25

30

35

40

45

Baseline

30

60

90

120

150

180

210

240

270

300

330

360

Day of Treatment

*

P <.001

41.5

16.1*

15.3*

14.7*

14.2*

14.3*

13.8*

14.3*

13.9*

13.9*

12.4*

13.1*

12.6*

39

Slide40

70/30 Serdex/d-MPH: Adverse Events

Reported at ≥5%: Gastrointestinal: decreased appetite, decreased weight, nausea, abdominal pain, dyspepsia, vomitingNeurologic/psychiatric: insomnia, anxiety, affect lability, irritability, dizzinessCardiovascular: increased blood pressure, tachycardiaData from 1-wk treatment phase of 150 patients 6-12 yr with ADHD:

Serdexmethylphenidate/Dexmethylphenidate PI.

Kollins

et al. J Child Adolesc Psychopharm. 2021;31:597.

n (%)

Serdex/

d-MPH

N = 74

Placebo

N = 76

Any TEAE

23 (31.1)

11 (14.5)

Headache

4 (5.4)

1 (1.3)

Abdominal pain, upper

3 (4.1)

1 (1.3)

Insomnia

2 (2.7)

1 (1.3)Pharyngitis

2 (2.7)0 (0.0)40

Slide41

Transdermal d-Amphetamine Patch

5 mg/9 hr

10 mg/9 hr

15 mg/9 hr

20 mg/9 hr

n (%)

7 (7)

35 (33)

42 (39)

23 (21)

Day 28

Wk 1

2

3

4

5

6

7

8

Dose-Optimization Period

Randomized, Double-Blind Treatment Period With Crossover

Screening and washout

Safety

follow-up

Optimal dose

Placebo

Placebo

Optimal dose

5 mg/

9 hr

5 mg/

9 hr

10 mg/

9 hr

5 mg/

9 hr

10 mg/

9 hr

15 mg/

9 hr

5 mg/

9 hr

10 mg/

9 hr

15 mg/

9 hr

20 mg/

9 hr

Cutler et al. APA 2021. Abstr P9-066.

41

Slide42

Transdermal d-AMPH Patch

Cutler et al. APA 2021. Abstr P9-066.

160

140

120

100

80

d-AMPH transdermal patch

Placebo

Hr Post Dose

LS Mean (SE) Number Correct

12

0

2

4

6

8

10

*

*

*

*

*

*

*

*

*Statistically significant difference.

42

Slide43

Allows Flexible Wear Time on Weekends

Mattingly et al. APSARD. 2022.

Treatment

d-ATS 20 mg

Time After Steady-state Dose (Hr)

Plasma Amphetamine Concentration (ng/mL)

150

0

50

100

60

40

20

150

0

50

100

2-Hr Weekend Wear Time

4-Hr Weekend Wear Time

43

Slide44

Transdermal d-AMPH Patch

No dropouts due to patch issues

Cutler et al. APA 2021. Abstr P9-066.

n (%)

Double-Blind Period

Randomized treatment phase

(1 week)

d-ATS (All Doses)

(N = 105)

Placebo

(N = 105)

Decreased appetite

13 (12)

2 (2)

Insomnia

6 (6)

5 (5)

Headache

6 (6)

4 (4)

Hyperkalemia

5 (5)

4 (4)

Vomiting

4 (4)

0 (0)Nasopharyngitis3 (3)2 (2)

Abdominal pain, upper

3 (3)

1 (1)Nausea3 (3)1 (1)Affect lability3 (3)0 (0)Tic

2 (2)0 (0)Irritability2 (2)1 (1)44

Slide45

Viloxazine XR

Approved for children aged 6-18 yr and now

for adults with ADHD

Yu et al. J Exp Pharmacol. 2010:12;285. Viloxazine PI.

PFC:

NE > DA > 5-HT

Nucleus Accumbens:

5-HT > NE > DA

Neurotransmitter Levels (% of Baseline)

Min

900

800

700

600

500

400

300

200

100

PFC

-90

-60

-30

0

30

60

90

120

150

180

210

240

270

NE (n = 5)

DA (n = 3)

5-HT (n = 5)

Glu (n = 6)

His (n = 6)

GABA (n = 5)

ACh (n = 3)

#

#

#

#

**

**

Neurotransmitter Levels (% of Baseline)

Min

Acb

500

400

300

200

100

270

240

210

180

150

120

90

60

30

0

-30

-60

-90

#

#

**

**

NE (n = 5)

DA (n = 5)

5-HT (n = 5)

Glu (n = 6)

His (n = 6)

GABA (n = 6)

ACh (n = 6)

45

Slide46

Viloxazine XR: 100-400 mg Daily

Pediatric data, 6-12 yr of ageImproved symptoms in 1 wkEqual improvement in inattentive and hyperactive symptoms

Nasser et al. Clin Ther. 2020;42:1452.

Change From Baseline in ADHD RS-5 Total Score LS Mean ± SE

Wk of Treatment

0

-2

-4

-6

-8

-10

-12

-14

-16

-18

-20

-22

Baseline

1

2

3

4

5

6

Placebo (n = 155)

100 mg/day viloxazine (n = 147)

200 mg/day viloxazine (n = 158)

*

*

*

*

*

ADHD RS-5 Measure

Placebo (n = 155)

Viloxazine

100 mg/day (n = 147) 200 mg/day (n = 158)

CFB, LS mean (SE)

Total score

-10.9 (1.14)

-16.6 (1.16)

-17.7 (1.12)

Inattention subscale

-5.7 (0.60)

-8.6 (0.62)

-9.2 (0.60)

Hyperactivity/impulsivity subscale

-5.5 (0.59)

-8.0 (0.60)

-8.7 (0.58)

46

Slide47

Viloxazine 200-600 mg Daily in Adult ADHD

Nasser et al. Psych Congress 2021. Poster.

Placebo

Viloxazine ER

-18

0

-2

-4

-6

-8

-10

-12

-14

-16

AISRS Total Score Change From BL

Wk of Treatment

BL

1

2

3

4

5

6

47

Slide48

Improvement in Both Inattentive and Hyperactive/Impulsive Symptoms

Nasser et al. Psych Congress. 2021.

Placebo

Viloxazine ER

-10

0

-2

-4

-6

-8

Inattention Score Change From BL

Wk of Treatment

BL

1

2

3

4

5

6

Placebo

Viloxazine ER

-10

0

-2

-4

-6

-8

Hyperactivity/Impulsivity Score

Change From BL

Wk of Treatment

BL

1

2

3

4

5

6

48

Slide49

Viloxazine XR Long-term Adult Data

Avg Dose:

400 mg daily

Nasser et al. Psych Congress. 2021.

Pivotal

Open-Label Extension

Mean CFB in AISRS Total Score (SEM)

0

-2

-4

-6

-8

-10

-12

-14

-16

-18

-20

-22

-24

-26

-28

BL

DW1

DW2

DW3

DW4

DW6

OW2

OW4

OW12

OW20

OW28

OW36

OW44

OW52

Pivotal

placebo

Pivotal

viloxazine ER

49

Slide50

Improvement

Nasser et al. Psych Congress. 2021.

Viloxazine XR ADHD Score and BRIEF-A

55

95

90

85

80

75

70

65

60

55

50

45

40

BRIEF-A GEC T-Score at Baseline

AISRS Total Score at Baseline

100

25

30

35

40

45

50

15

5

-5

-15

-25

-35

-45

-55

CFB BRIEF-A GEC T-Score at EoS (%)

AISRS Total Score at Baseline

25

-110

-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

0

10

20

30

40

50

Slide51

Other Groups With Executive Function Deficits?

P

<.001 change from baseline.

*

New-Onset Executive Function Difficulties at Menopause:

A Possible Role for Lisdexamfetamine

Epperson et al. Psychopharmacology. 2015;232:3091.

50.0

45.0

40.0

35.0

30.0

25.0

20.0

15.0

10.

5.0

0.0

BADDS Total Score

Baseline

Active

Placebo

51

Slide52

Tools in the “Toolbox”

Get to know 1 or 2 long-acting MPHs, 1 or 2 long-acting AMPHs and 1 or 2 nonstimulantsConsider onset and durationTitrate to optimal effect vs side effectsWatch for breakthrough symptoms throughout the day, especially in mornings and eveningsUse short-acting stimulants sparingly and avoid in College studentsMonotherapy in adultsWhen concerned about abuse, misuse or diversion

52

Slide53

Digital Therapeutics?

Lumosity, Akili, Atentiv, Pear, and othersPotential cognitive enhancers in children and adults with ADHD?53

Slide54

Digital Therapeutics

EndeavorRx

54

Slide55

Digital Therapeutics

Examples of Lumos “Games”

Attention

Attention

and

Flexibility

Attention

and

Flexibility

Lumos Labs.

Activities target attention and/or flexibility

55

Slide56

Digital Therapeutics

Lumosity, Akili, Atentiv, and othersPotential cognitive enhancers in children and adults with ADHDQuestionsDo they work with ADHD medications?Akili adult trial to evaluate effects with and without ADHD medicationsDo they improve core ADHD symptoms or just specific cognitive aspects?

Lumosity to look at ADHD-RS, BRIEF, WFIRSDo they work with comorbidities: ASP, MDD, post COVID-19?Akili with pilot data in these conditions

Do they work in adults?Controlled data thus far only in childrenLumosity with large “big data” set in adults with ADHD

56

Slide57

Key Summary Points

Excessive screen time and social media use have been shown to worsen processing speed and increase ADHD symptoms Recent data from the MTA study show that 90% of children with ADHD will continue to have symptoms into adulthood Unrecognized or untreated ADHD dramatically increases mortality rates, worsens school and job performance, and impacts overall daily functionHolistic ADHD treatment has some of the biggest treatment effects of any intervention in medicine 57

Slide58

Go Online for More PCE Activities!

Download all the slides from this meeting:

practicingclinicians.com/content/psychiatry-update-2022-for-apps

More FREE CE/CME Activities Available at:

practicingclinicians.com