www.mghcme.org

Treating Disruptive Behavior in Children

with ASD

January 22, 2017

Lawrence Scahill, MSN, PhD Professor of Pediatrics

Marcus Autism Center

Emory University

www.mghcme.org

Disclosures

Consultant

• Roche

• Neuren

• Supernus

Rater Training • Bracket

Royalties

• Oxford, Guilford

Completed NIH-funded Multisite Trials in ASD past 20 yrs Study N Target Ages Results Published

Risperidone vs placebo

101 Irritability (tantrums, Aggression & SIB)

5-17 A > P +++

NEJM, 2002

Methylphenidate vs placebo

66 Hyperactivity 5-14 A> P +

Arch Gen Psych, 2005

Citalopram vs placebo

149 Repetitive Behavior 5-17 A=P Arch Gen Psych, 2009

RIS vs RIS + Parent Training

124 Irritability & Adaptive Behavior

4-13 COMB > RIS

J Am Acad Child Psych, 2009, 2012, 2016

Guanfacine vs placebo

62 Hyperactivity 5-14 A > P ++

Am J Psych, 2015

Parent Training vs Parent Education

180 Irritability & Adaptive Behavior

3-7 PT > PE ++

JAMA, 2015; J Am Acad Child Psych, 2016

www.mghcme.org

Characteristics of Participants RUPP Trials By Sex (N=533; Age 7.0 ± 2.5)

Characteristic Male Female

N (%) 457 (85.7%) 76 (14.3%)

IQ < 70 190 (43.3%) 35 (49.3%)

IQ ≥ 70 249 (56.7%) 36 (50.7%)

Mean (SD) Mean (SD)

Vineland Communication 65.9 ±22.3 61.8 ± 24.6

Vineland Socialization 62.5 ± 16.2 59.5 ± 16.4

Vineland Daily Living 59.8 ± 23.5 57.3 ± 26.1

Aberrant Behavior Checklist

Irritability 24.1 ± 8.5 24.1 ± 9.2

Social Withdrawal 14.1 ± 8.8 14.1 ± 8.7

Stereotypy 8.0 ± 5.3 7.9 ± 5.6

Hyperactivity 33.1 ± 8.8 30.5 ± 8.8

Inappropriate Speech 5.9 ± 3.5 5.9 ± 3.8

CYBOCS Total 13.9 ± 3.9 13.8 ±3.9

www.mghcme.org

RUPP Autism Network: Irritability Scale

RUPP Autism Network, 2002. NEJM, 347(5): 314-321.

0

5

10

15

20

25

30

0 2 4 6 8

Week

AB

C I

rrit

ab

ilit

y T

ota

l

Risperidone mean

Placebo mean

Mean =1.8 mg/day; ES=1.3

www.mghcme.org

Clinical Global Impression-Improvement

1 = Very Much Improved

2 = Much Improved

3 = Minimally Improved

4 = No Change

5 = Minimally Worse

6 = Much Worse

7 = Very Much Worse

www.mghcme.org

CGI-Improvement: RIS vs Placebo

Group Positive

Response

Negative

Response

RIS 40 (75.5%) 9 (24.5%)

Placebo 6 (11.5%) 46 (88.5%)

p< 0.001

RUPP Autism Network. NEJM, 347(5): 314-321.

www.mghcme.org

Risperidone only vs Risperidone + Parent

Training (Aman et al., 2009; Scahill et al., 2012)

Design

• 6-month randomized trial

•124 subjects (age 4 to 13 years)

• Random assignment

– risperidone only (N=49) or

– risperidone + Parent training (N=75)

J Am Acad Child Adolesc Psych, 2009, 2012

www.mghcme.org

ABC Irritability

10

12

14

16

18

20

22

24

26

28

30

BL Week 8 Week 16 Week 24

HS

Q S

co

re

MED

COMB

ES = .48

www.mghcme.org

Weight Gain and Metabolic Consequences of Risperidone in Young Children With Autism

Spectrum Disorder

Scahill L, Jeon S, Boorin SJ, McDougle CJ, Aman MG, Dziura J, McCracken JT, Caprio S, Arnold LE, Nicol G, Deng Y, Challa SA, Vitiello B (2016)

JAmAcademy Child & Adolescent Psychiatry

www.mghcme.org

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

BL Wk 8 Wk 16 Wk 24

Normal Wt

Over Wt

Obese

Column1

% s

ub

ject

s b

y W

t g

rou

p

Change in Weight Category over 24 Weeks (N=97)

www.mghcme.org

RUPP #2: Risperidone and Risperidone + Parent Training (N=97)

Weight, Waist Circumference: Baseline & Week 24

Baseline

Mean (SD)

Week 24

Mean (SD)

Measure Baseline Week 24 Mean Change (SD)*

Weight in kg 29.3 (11.5) 34.0 (12.6) 5.3 (3.4)

Waist circum. in cm 60.7 (10.4) 66.8 (11.3) 6.1 (5.18)

* Statistically significant

Growth curves for children with ASD exposed to risperidone (N=97) Whole sample with 95% CI and subgroup by reported appetite

Rubinetwork.org

www.mghcme.org 15

www.mghcme.org

RUBI: Study Objectives and Design

• Efficacy Study

– Parent Training vs Parent Education*

– Children (3-7 yrs) with ASD & DBP

• 24 Week Trial

– At Wk 24, a blinded independent evaluator (IE)

classified subject as + or - response

• Follow-up:Wk 36 & 48 (not discussed here)

*active comparator

www.mghcme.org

Participants

• 3-0 to 6-11 years

• N=180

• DSM-IV Diagnosis of ASD

• > 15 on the parent-rated Aberrant Behavior

Checklist Irritability (ABC-I) subscale

• Stable medication/treatment plan

www.mghcme.org

Program Structure

Parent Training

• Week 1-16

- 11 Core Sessions

- 2 Home Visits

- Up to 2 Optional Sessions

• toileting, feeding, sleep, time out

Parent Education

• Week 1-24

- 12 Core Sessions

- 1 Home Visit

Both treatments: 1:1 with parent, using the same format

www.mghcme.org

Primary & Key Secondary Outcome Measures

• Parent-reported outcomes

– Aberrant Behavior Checklist-Irritability subscale

– Vineland

• Blinded Independent Evaluator

– Parent Target Problems via parent interview

– Improvement item of the Clinician Global Impression

• Much/Very Much Improved = + Response

www.mghcme.org

Baseline Characteristics

• 88% boys

• mean age = 4.7 +1.1 years

• 74% IQ >70

• 87% Caucasian

• 14% Hispanic

• 69% Autistic Disorder

• 46% in Regular Education class

• 20% on stable psychotropic medication

• 88% two-parent family

www.mghcme.org

ABC-I LSM Outcomes

10

12

14

16

18

20

22

24

Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24

Parent Training

Parent Education

Pp < .001

www.mghcme.org

CGI Positive Response

0

10

20

30

40

50

60

70

80

Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24

Parent Training

Parent Education

p < .001

www.mghcme.org

Vineland Daily Living Skills: Standard Scores

73

74

75

76

77

78

79

80

81

82

83

84

Baseline Week 24

Parent Training

Parent Education

www.mghcme.org

Conclusion

• Largest RCT of a behavioral intervention for

children with ASD.

• Structured, relatively brief PT program was

superior to PEP for disruptive behavior and

daily living skills

www.mghcme.org

Future Directions

• Dissemination

– Getting the word out: not enough

• Implementation

– Reach: access in clinics & schools

www.mghcme.org

Thank You