Treating Disruptive Behavior in Children with ASD January 22, 2017
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
www.mghcme.org
Completed NIH-funded Multisite Trials in ASD past 20 yrs Study
N
Target
Ages
Results Published
Risperidone vs placebo
101 Irritability (tantrums, 5-17 Aggression & SIB)
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 124 Irritability & Training 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
Characteristics of Participants RUPP Trials By Sex (N=533; Age 7.0 ± 2.5) Characteristic Male Female
N (%) IQ < 70 IQ ≥ 70 Vineland Communication Vineland Socialization Vineland Daily Living Aberrant Behavior Checklist Irritability Social Withdrawal Stereotypy Hyperactivity Inappropriate Speech CYBOCS Total
457 (85.7%) 190 (43.3%) 249 (56.7%) Mean (SD) 65.9 ±22.3 62.5 ± 16.2 59.8 ± 23.5
76 (14.3%) 35 (49.3%) 36 (50.7%) Mean (SD) 61.8 ± 24.6 59.5 ± 16.4 57.3 ± 26.1
24.1 ± 8.5 14.1 ± 8.8 8.0 ± 5.3 33.1 ± 8.8 5.9 ± 3.5
24.1 ± 9.2 14.1 ± 8.7 7.9 ± 5.6 30.5 ± 8.8 5.9 ± 3.8
13.9 ± 3.9
13.8 ±3.9 www.mghcme.org
RUPP Autism Network: Irritability Scale Risperidone mean
ABC Irritability Total
30
Placebo mean
25 20 15 10 5
Mean =1.8 mg/day; ES=1.3
0 0
2
4
6
8
Week
RUPP Autism Network, 2002. NEJM, 347(5): 314-321. 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 RIS
Positive Response 40 (75.5%)
Negative Response 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
HSQ Score
ABC Irritability 30 28 26 24 22 20 18 16 14 12 10
MED COMB
BL
Week 8
Week 16
ES = .48
Week 24
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
Change in Weight Category over 24 Weeks (N=97)
% subjects by Wt group
0.7 0.6 0.5 Normal Wt
0.4
Over Wt
0.3
Obese
0.2
Column1
0.1
0 BL
Wk 8
Wk 16
Wk 24
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RUPP #2: Risperidone and Risperidone + Parent Training (N=97) Weight, Waist Circumference: Baseline & Week 24
Measure
Baseline Mean (SD) Baseline
Week 24 Mean (SD) 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
www.mghcme.org
Growth curves for children with ASD exposed to risperidone (N=97) Whole sample with 95% CI and subgroup by reported appetite
Rubinetwork.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
Parent Education • Week 1-24 - 12 Core Sessions - 1 Home Visit
• toileting, feeding, sleep, time out
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 24 22 20
Pp < .001
18
Parent Training Parent Education
16 14 12 10 Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24
www.mghcme.org
CGI Positive Response 80 70
60 50
p < .001 Parent Training
40
Parent Education
30 20 10 0 Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24
www.mghcme.org
Vineland Daily Living Skills: Standard Scores 84 83 82 81 80 79
Parent Training
78
Parent Education
77 76 75 74 73 Baseline
Week 24
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
www.mghcme.org
www.mghcme.org
Disclosures Consultant Roche • Neuren • Supernus •
Rater Training •
Bracket
Royalties •
Oxford, Guilford
www.mghcme.org
Completed NIH-funded Multisite Trials in ASD past 20 yrs Study
N
Target
Ages
Results Published
Risperidone vs placebo
101 Irritability (tantrums, 5-17 Aggression & SIB)
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 124 Irritability & Training 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
Characteristics of Participants RUPP Trials By Sex (N=533; Age 7.0 ± 2.5) Characteristic Male Female
N (%) IQ < 70 IQ ≥ 70 Vineland Communication Vineland Socialization Vineland Daily Living Aberrant Behavior Checklist Irritability Social Withdrawal Stereotypy Hyperactivity Inappropriate Speech CYBOCS Total
457 (85.7%) 190 (43.3%) 249 (56.7%) Mean (SD) 65.9 ±22.3 62.5 ± 16.2 59.8 ± 23.5
76 (14.3%) 35 (49.3%) 36 (50.7%) Mean (SD) 61.8 ± 24.6 59.5 ± 16.4 57.3 ± 26.1
24.1 ± 8.5 14.1 ± 8.8 8.0 ± 5.3 33.1 ± 8.8 5.9 ± 3.5
24.1 ± 9.2 14.1 ± 8.7 7.9 ± 5.6 30.5 ± 8.8 5.9 ± 3.8
13.9 ± 3.9
13.8 ±3.9 www.mghcme.org
RUPP Autism Network: Irritability Scale Risperidone mean
ABC Irritability Total
30
Placebo mean
25 20 15 10 5
Mean =1.8 mg/day; ES=1.3
0 0
2
4
6
8
Week
RUPP Autism Network, 2002. NEJM, 347(5): 314-321. 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 RIS
Positive Response 40 (75.5%)
Negative Response 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
HSQ Score
ABC Irritability 30 28 26 24 22 20 18 16 14 12 10
MED COMB
BL
Week 8
Week 16
ES = .48
Week 24
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
Change in Weight Category over 24 Weeks (N=97)
% subjects by Wt group
0.7 0.6 0.5 Normal Wt
0.4
Over Wt
0.3
Obese
0.2
Column1
0.1
0 BL
Wk 8
Wk 16
Wk 24
www.mghcme.org
RUPP #2: Risperidone and Risperidone + Parent Training (N=97) Weight, Waist Circumference: Baseline & Week 24
Measure
Baseline Mean (SD) Baseline
Week 24 Mean (SD) 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
www.mghcme.org
Growth curves for children with ASD exposed to risperidone (N=97) Whole sample with 95% CI and subgroup by reported appetite
Rubinetwork.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
Parent Education • Week 1-24 - 12 Core Sessions - 1 Home Visit
• toileting, feeding, sleep, time out
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 24 22 20
Pp < .001
18
Parent Training Parent Education
16 14 12 10 Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24
www.mghcme.org
CGI Positive Response 80 70
60 50
p < .001 Parent Training
40
Parent Education
30 20 10 0 Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24
www.mghcme.org
Vineland Daily Living Skills: Standard Scores 84 83 82 81 80 79
Parent Training
78
Parent Education
77 76 75 74 73 Baseline
Week 24
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
www.mghcme.org
