ADHD comorbidity in Autism Spectrum Disorders - Child & Adolescent Psychopharmacology
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Child & Adolescent Psychopharmacology
March 21, 2021 Sunday
ADHD comorbidity in
Autism Spectrum Disorders
T. Atilla Ceranoglu, MD
Assistant Professor of Psychiatry
Harvard Medical School, Boston
ADHD, ASD and Autistic Traits • ASD and ADHD comorbid presentation • Autistic traits in ADHD • Treatment implications
N e u r o d e v e l o p m e n t a l D i s o r d e r s (ASD and ADHD)
Shared Characteristics Distinct Symptom Triad
ADHD ASD ASD ADHD
Prevalence in - Impaired social interaction - Inattention
6-8% 2%
Children
Heritability Estimates 75% 90% - Impaired social communication - Hyperactivity
Male:Female Ratio 2.5:1 4:1
Manifest early in life Yes Yes - Restricted Repetitive Behaviors - Impulsivity
Lifelong Disorders Yes Yes
ADHD
ASD
ASD & ASD Traits in ADHD
ASD Traits
ASD Diagnosis
Clark et al., 1999
Joshi et al., 2013
*Kochhar et al., 2011
*Cooper et al., 2014 Jensen & Steinhausen, 2014
*Grzadzinski et al., 2011
Faber et al., 2010
*Mulligan et al., 2009
Reirsen et al., 2007 Larson et al. 2011
18% - 63% 2% - 15%
*Kotte et al., 2013 Smalley et al. 2007
Percentage 0 10 20 30 40 50 60 70
Percentage 0 2 4 6 8 10 12 14 16
*ADHD Youth with no prior diagnosis of ASD
ASD ADHD
Comorbid ASD in up to 15% of the ADHD PopulationsADHD Symptoms & Diagnosis in ASD referrals
ADHD Symptoms ADHD Diagnosis
Sverd et al., 1995 Joshi et al., 2014
Lee & Ousley, 2006 Sinzig et al., 2009
Sturm, et al., 2004 DeBruin et al., 2007
Tani et al., 2006
Mattila et al., 2010
Yoshida &…
Leyfer et al., 2006
Holtmann et al.,…
Gjevik et al., 2011
Goldstein &…
49% - 88% 28% - 75%
Gadow et al., 2004 Simonoff et al., 2008
Percentage 0 10 20 30 40 50 60 70 80 90 100 Percentage 0 10 20 30 40 50 60 70 80 90 100
ASD ADHD
Comorbid ADHD in up to 75% of the ASD PopulationsADHD Symptom Profile in ASD
*
ADHD+ASD ADHD
100
* ** **
80
Percent with Symptom
60
40
20
0
Careless/ Doesn't listen Dif ficulty Loses Forgetful Fidgets/ Physically On the go/ Blurts out Interrupts/
Sloppy organizing thin gs in daily activities Squirms restless Driven by a answers Intrudes
tasks/ activities motor
Inattentive Symptoms Hyperactive/Impulsive Symptoms
*p≤0.01, **p≤0.001Profile of ADHD in ASD
Presentation of ADHD # of ADHD Symptoms
75 *
** 16
59% 14
60 57% 14 13
12
Mean # of Symptoms
45 41% 10
Percentage
33% * 8 8
8 6
30 5
6
15 8% 4
2% 2
0 0
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tiv ASD+ADHD
rac
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ASD+ADHD
pe
pe
ADHD
Hy
Hy
ADHD
More robust form of ADHD (combined) presents more frequently in ASDAdditional ADHD-Related Symptoms
Control (N=106) ADHD (N=105) ADHD+CBCL-AT (N=26)
100 a***b* a*** a***b***
90 a***b* a***b*
80
70
60
a*** a***b*
% 50
40 a vs. Controls
a*** b vs. ADHD
30
***pA D H D Tr e a t m e n t H i s t o r y i n A S D
50
*
43%
41%
40
*
30 27%
Percentage
26%
24%
20 * 18%
15%
10
5%
0
Treatment Counseling Pharmacotherapy Only Counseling +
Naïve Only Pharmacotherapy
ASD+ADHD ADHD
Statistical Significance: *p≤0.05, **p≤0.01, ***p≤0.001
ADHD is undertreated in youth with ASDI mpl i c a ti ons of Unrec ogni zed Comor bi di ty
ADHD ASD
• Impairs intellectual/school • Receive inappropriately
performance aggressive treatment for
psychopathology
• Further compromises social
functioning • Failure to recognize atypical
precipitants that negatively
• Interferes with ASD specific
affects psychopathology
behavioral interventions
• Leads to attempts to treat ADHD • Failure to receive treatment
specific for ASD
with ASD specific interventions
• Failure to receive disorder • Missed opportunity to implement
early interventions for ASD
specific treatment
• Increased risk for developing
other psychiatric conditions
• disruptive behaviors
• substance abuseADHD symptoms in ASD Youth • ADHD symptoms are common in ASD (>50%) • The clinical presentation of ADHD in ASD youth is typical of the disorder • ASD youth with ADHD have significantly more impaired psychosocial functioning • Significantly fewer ASD youth receive targeted treatment for ADHD
Treatment Trials in AUTISM
IQ: Low Versus High-functioning
Tx. Target: Symptoms Versus Syndromes
• Hyperactivity
• Irritability/Aggression
• Repetitive Behaviors/Anxiety
• Sleep dysregulation
Emerging Evidence: Pharmacotherapy for core features of AutismA D H D Tre a t m e n t S t u d i e s i n A S D
Controlled Trials
ADHD Med Class Total N≥10 NCONTROLLED STUDIES for ADHD in AUTISM SPECTRUM DISORDER - Methylphenidate
Design Age Tota Dose
RCT [Duration] [years] l(N) HF [mg/day] Efficacy Tolerability Comments
Sign. ⇊ TEAE: Buccal-lingual All participants with speech delay
Ghuman Pre-
Crossover 15 ±5 Hyperactivity Movements Response less than typically expected
et al., school 12 NR
[4-Week] [5 – 20] -CPRS Dose-LAE: 9 (64) Improvement in social behaviors
2009 [3-5]
RR: 50%; ES: 0.97 Tx-LAE: 1 (6) No worsening of ASD
Pearson Sign. ⇊ ADHD TEAE: Insomnia, Typically expected response
0.35 -
et al., Crossover Children -CTRS ↓Appetite D/c of MPH-IR afternoon dose d/t AEs
24 rd
2/3 0.75
2013 [4-Week] [7-12] RR: 67% Dose-LAE: 5 (21) Improvement in social skills
mg/kg
[MPH-ER] ES: NR Tx-LAE: None No worsening of ASD, Mood, or Anxiety
Sign. ⇊ TEAE: Insomnia, Majority of patients with ID & nonverbal
Hyperactivity ↓Appetite, Emotional Significant level of irritability at baseline
RUPP, Crossover Children 7.5 – 50
66 8% -ABC-H outburst, Irritability Response less than typically expected
2005 [4-Week] [5–13] mg
RR: 49% Dose-LAE: 16 (24) ↑↑ fr. of emotional lability AE
ES: 0.48 Tx-LAE: 13 (18) No worsening of ASD
Sign. ⇊
Handen TEAE: P=NR Significant level of irritability at baseline
Crossover Children Hyperactivity
et al., 13 8% NR Dose-LAE: 2 (15) ↑↑ fr. of mood dysregulation AE
[3-Week] [5-11] -CTRS-H
2000 Tx-LAE: 1 (1) No worsening of ASD
RR: 61%; ES: NR
Sign. ⇊
Quintana TEAE: None No mood dysregulation with Tx
Crossover Children 0.4 - 0.7 Hyperactivity
et al., 10 30% Dose-LAE: None No difference in HD vs. LD response
[6-Week] [7-11] mg/kg -ABC-H/ CTRS-H
1995 Tx-LAE: None No worsening of ASD
ES: NR
NR=Not Reported; HF=High-Functioning; ID=Intellectual Disability; ES=Effect Size; RR=Response Rate; AE=Adverse Events;
TEAE=Treatment Emergent AE; Dose-LAE=Dose-Limiting AE; Tx-LAE=Treatment-Limiting AE; CTRS=Conners' Teacher Rating Scale;
CPRS=Conners' Parent Rating Scale; ABC-H=Aberrant Behavior Checklist-Hyperactivity subscaleMethylphenidate - RUPP Trial
Crossover RCT in ASD Youth with Hyperactivity
• Diagnoses: ASD + Hyperactivity (moderate-severe)
• Ages: 5-14 years (majority with Intellectual Disability)
Tolerability Phase RCT Phase Open-Label Phase
• 3 Phases:
1 week; n=72 4 weeks; n=66 8 weeks; n=35
• MPH Dose (TID):
• Low: 0.125mg/kg/day
• Medium: 0.25 mg/kg/day
• High 0.5 mg/kg/dayM e t h y l p h e n i d a t e – RU P P Tr i a l
Efficacy
Crossover Phase Response: Parent-rated ABC-Hyperactivity Subscale
35
M e a n A B C H y p e ra c tiv ity S u b s c a le S c o re s
∗
30 p = 0.03 *p = 0.003
Effect = 0.3 p < 0.0001 Effect = 0.4
25 Effect = 0.5
*Parents reported
20 increased social
15 withdrawal
on high dose of MPH
10
5
0
Baseline( Placebo( Low( Medium( High(
_______________________________________
MPH DoseM e t h y l p h e n i d a t e – RU P P Tr i a l
Efficacy
Continuation Phase Response: Informant-rated ABC-Hyperactivity Subscale
Crossover Open-Label Continuation
40
35
Mean ABC Hyperactivity Subscale Scores
30
25
20
15
10
5
Parent Teacher
0
Baseline Crossover Phase Week 4 Week 8
@ Best DoseM e t h y l p h e n i d a t e – R U P P Tr i a l
Efficacy
ADHD Response
Rate of Response: 50% 80
(≤2 CGI-I + ABC-H ⇊ >25-30%) 70%
60
Effect Size: 0.20 – 0.54
Rate of response
50%
(vs. 0.35 – 1.31 in MTA trial)
ADHD response independent of: 40
• Level of IQ
• Subtypes of ASD 20
Additional Response*
Improvement in: - Joint Attention 0
- Self/Affect Regulation TD ASD
MPH is less effective for ADHD in children with ASD than typically expected?
Comorbidity unknown in a patient population predominantly with low functioning
autismM e t h y l p h e n i d a t e – R U P P Tr i a l
To l e r a b i l i t y
Common AEs:
• Decreased appetite
• Initial insomnia 30
• Irritability
• Emotional outbursts 25
No exacerbation of stereotypes or
Rate of Dropout
20 18%
repetitive behaviors
15
Dropout: 18% (13/72)
10
• All dropout d/t treatment-limiting Aes
5
• 50% (6/13) dropout d/t inability to 1.5%
tolerate test dose 0
• 50% (6/13) dropout d/t irritability TD ASD
MPH is associated with more frequent adverse effects in children with ASD
than typically expected (comorbidities??)Methylphenidate - Extended Release
Crossover RCT in ASD Children with ADHD
ASD + ADHD: N = 24
[Autistic Disorder=19/24; ADHD=19/24]
Male: 79%
Mean Age [Range] : 9 ±1.7 [7–12]
Mean IQ [Range] : 85 ±17 [46-112]
3 Trial Phases:
1. Placebo phase: 1 Week (N=24)
2. Tolerability phase: 2 day each on test doses of 3 different strengths of MPH (N=24)
3. Crossover Phase: 3 Week (N=24)
MPH-ER Dose Schedule
Duration MPH Dosing Morning Afternoon
[Week] (mg/Kg/day) MPH-ER dose MPH-IR dose
1 Low dose 0.2 0.15
1 Medium dose 0.35 0.25
1 High dose 0.5 0.3Methylphenidate - Extended Release
Dose comparison, RCT in children with ASD and ADHD
ASD + ADHD: N = 27
Male: 93%
Mean Age [Range] : 9 ±2.9 [5-14]
Study Design
- 6 weeks, flexible dosing schedule
- 3 different doses: Very Low (≤10mg/day), Low (≤20 mg/day) Moderate (≤ 40 mg/day)
Low dose Medium dose
N=9 N=18
Mean dose 9.7mg/day Mean dose 20.28 mg/dayMethylphenidate - Extended Release Efficacy Parent (ABC; p
3/20/21
O LT o f M P H i n A d u l t s w i t h H F - A S D
15 Adults aged 19-34 years (Mean age: 25 ±4.5 years)
• Intact intellectual ability (IQ Range: 99 – 144)
• Met the DSM-V criteria for ASD and ADHD
• At least moderate level of severity for ASD and ADHD
(SRS=≥85; AISRS=≥24; & respective CGI-S ≥4)
• Not sign. symptoms of anxiety or mood dysregulation
Study Medication (MPH-ER Liquid Formulation: 25mg/5mL)
Flexible Dose Titration Schedule Dose at Endpoint
Duration QAM Dose Mean dose: 49 ±15 mg/day
Initial dose: 5 mg/day 60 mg/day 08 (53%)
Individual
Titration phase (0-3 weeks): 5-60 mg/day 50 mg/day 02 (13%)
Doses:
Maintenance phase (4-6 weeks): Max. achieved dose 20-40 mg/day 05 (33%)3/20/21
Tr e a t m e n t R e s p o n s e : A D H D S y m p t o m s
Clinician-Rated Adult Investigator Symptom Report Scale (AISRS)
Patient-Rated Adult Self-Report Scale (ASRS)
AISRS ASRS
45
41.1 ±12.1 [MCASRS= -8.2 ±15.3; Z= -3.67;
40 [MCASRS= -4.8 ±9.9; Z= -2.08;
p3/20/21
Treatment Response: Response Rate
100 93%
90
80% 80%
80
70
Percent at Endpoint
60
50
40
30
20
10
0
ADHD-CGI-I ≤2 AISRS-Total Reduction ADHD-CGI-I ≤2 +
≥30% AISRS Reduction ≥30%3/20/21
Tr e a t m e n t R e s p o n s e : A D H D S y m p t o m s
AISRS % Score Reduction at Trial Completion
100% 93% 93%
89%
90%
80%
69% 70%
AISRS % Score Reduction
69%
70% 63% 62%
65%
59%
60% 54%
50%
50% 46% 44%
40%
30%
20%
8%
10%
0%
Subject # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Max. daily dose (20) (20) (30) (40) (40) (50) (50) (60) (60) (60) (60) (60) (60) (60) (60)
( mg/day)
Non-linear dose response3/20/21
Treatment Response: Associated Psychopathology
[MC= -3.5 ±4.5; Z= -2.5; p=0.01] [MC= -3 ±4.5; Z= -2; p=0.06]
10
9 ±6
8.5 ±5.5
8
6 5.5 ±6 5.5 ±6.5
Mean Score
4
2
0
HAM-A HAM-D
Baseline Endpoint
MC=Mean Change; HAM=A=Hamilton Anxiety Scale; HAM-D=Hamilton Depression Scale3/20/21
MPH ER – Adverse Events
Adverse Events (Mild-Moderate Severity)
Headache 53
Insomnia 33%
Anxiety 33%
Decreased Appetite 27%
Fatigue 13%
Irritability 13%
Percentage 0 10 20 30 40 50 60
Experienced any AEs: N=13 (87%)
Serious AEs: N=1 (Report of OD on Benadryl [suicide attempt] at week-6. Prior h/o SI.
[Upon completion continued tx. with study medication])
Treatment Limiting AEs: N=1 (Terminated at week-3 @ 20 mg/day d/t AEs: headaches, palpitations, jaw
pain, & insomnia [resolved on d/c])
Titration Limiting AEs: N=7 (Headache[N=3], High Blood Pressure[N=2], Worsening of Anxiety[N=1], Nausea[N=1],
Fatigue[N=1])3/20/21
MPH ER – Adverse Events
Baseline Endpoint Difference p-value
Body weight (kg) 86 ±26.5 84.5 ±26.5 -1.45 ± 2.4 0.01 [-2.59]
Pulse (bpm) 73 ±9.3 82 ±14.3 9 ±13.4 0.007 [2.69]
Blood pressure (mmHg)
Systolic 121.5 ±10.2 123 ±11.6 1 ±10.7 0.93 [0.08]
Diastolic 78.5 ±10.0 78.7 ±11.4 0.2 ±7.6 0.71 [0.37]
Pulse & Blood Pressure 10
Tachycardia (heart rate >100 beats/min) N=3
5
High Blood Pressure (systolic BP ≥140 N=2 5
Change in Body Weight (Ibs)
1.6 1.4 1
mm/Hg &/or diastolic BP ≥90 mm/Hg) 0
0
No QTc prolongation on ECG observed -1.2
-2.4 -1.6
(>460 or >60 ms increase from baseline) -5 -3.4 -4
-5.9 -6.5 -7
-10 -7.4
-15
-17
-20
Subj ect #
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Max. (20) (20) (30) (40) (40) (50) (50) (60) (60) (60) (60) (60) (60) (60) (60)
dai l yMethylphenidate response in ASD
• Modest response, less than observed in TD children
– Less effective in treating hyperactivity symptoms
– Although dose cannot be predicted, may respond to lower dose of
MPH than expected (0.3mg/kg/day)
• May also improve Social Interaction (joint attention)
• Adverse effects are more prevalent and could be dose-dependent
• ADHD Response in a carefully chosen population, screened for
comorbidities is same as that in typically developing children
RUPP Autism Network, 2005; DiMartino et al., 2004; Handen et al., 2000; MTA Trial, 2001CONTROLLED STUDIES for ADHD in AUTISM SPECTRUM DISORDER – Non-Stimulants
ATOMOXETINE
Design Age Total Dose
RCT [Duration] (Yrs) [N] HF (mg/day) Efficacy Tolerability Comments
Significant level of baseline irritability
Handen ⇊ ADHD ↓Appetite
Parallel 1.4 ±0.5 Efficacy less than typically expected
et al., 5-15 128 16% (SNAP-IV) Dose-LAE: None
[10-Week] mg/kg Typically expected tolerability
2015 RR 47%; ES 0.8 Tx-LAE: 5 (8) vs. 10 (16)
No worsening of ASD, Mood, or SI
⇊ ADHD Nausea, ↓Appetite, Early Significant level of baseline irritability
Harfterkamp
Parallel 0.5-1.2 ADHD-RS [Mean↓ 8] waking, Fatigue Efficacy less than typically expected
et al., 6-16 97 6%
[8-Week] mg/kg RR 21% [P=NS]; Dose-LAE: None Typically expected tolerability
2012
ES NR Tx-LAE: 1 (2) vs. 0 No worsening of ASD
Upset stomach, N&V,
Arnold ⇊ Hyperactivity Fatigue, Tachycardia
Crossover 44 ±22 Significant level of baseline irritability
et al., 5-15 16 6% ABC-H [Mean↓= 5]
[12-Week] 20-100 Dose-LAE: None All participants experienced GI AEs
2006 RR 57%; ES 0.9 Tx-LAE: 1 (6) vs. 0
GUANFACINE
Design Age Total Dose
RCT [Duration] (Yrs) [N] HF (mg/day) Efficacy Tolerability Comments
Drowsiness, Fatigue, Significant level of baseline irritability
Scahill Chil ⇊ Hyperactivity ↓Appetite, Dry mouth, Typically expected efficacy
dren Emotional/ tearful,
et al., Parallel 3 ABC-H [%↓= 44] Irritability, Anxiety AEs at higher frequency than typically
62 37%
2015 [8-Week] 5-14 1-4 RR 50%; ES Dose-LAE: 9 (30) vs. 5 expected
[GFC-ER] 1.67 (16) Mood & anxiety related AEs
Tx-LAE: 4 (13) vs. 0 No worsening of ASD
NR=Not Reported; HF=High-Functioning; ES=Effect Size; RR=Response Rate; AE=Adverse Events; Dose-LAE=Dose-Limiting AE; Tx-
LAE=Treatment-Limiting AE; SNAP-IV=Swanson, Nolan, & Pelham Rating Scale; ABC-H=Aberrant Behavior Checklist-Hyperactivity subscale;
ADHD-RS=Attention Deficit Hyperactivity Disorder-Rating ScaleAtomoxetine
8-week RCT
• 97 children with ASD + ADHD diagnoses
– 6-17 years (10 ±2.5)
– 37% ADHD treatment naïve
– IQ: 90 ±16 (61-138)
– NO concomitant psychotropic medications
• Atomoxetine (BID) dosing:
- Week-I: 0.5 mg/kg/day
- Week-II: 0.8 mg/kg/day
- Week-III: 1.2 mg/kg/dayAtomoxetine - Efficacy
Efficacy
45
40
ADHD-RS Mean Score
Clinician Rated
35
(p < 0.001)
ADHD-CGI-I ≤2
30 ATX[21%] ⊁ PBO[9%] (p=0.14)
Atomoxetine
25
Placebo
20
Baseline Week 8
Less than expected magnitude of response to atomoxetine
(ADHD-RS mean reduction: ASD[8] vs. TYP[13-19])Atomoxetine – Tolerability
- Rate of AEs: ATX 81% vs. PBO 65%
- Nausea (29%ATX vs. 8%PLO; p=0.009)
- Decreased appetite (27%ATX vs. 6%PLO; p=0.006)
- Fatigue (22%ATX vs. 8%PLO; p=0.05)
- Early Morning Awakening (10%ATX vs. 0%PLO; p=0.03)
- Treatment-limiting side effect: ATX 1/48 (fatigue) vs. PBO 0/49
- No exacerbation of stereotypes or other repetitive behaviors
- No serious side effects
Atomoxetine is associated with more frequent adverse
effects in children with ASD compared to reported rates in
children with typical developmentA t o m oxe t i n e & P a re n t Tr a i n i n g • 10-week RCT • 128 children with ASD + ADHD – 5-14 yrs (8 ±2); 85% male – IQ 61-138 (82 ±24) – 55% with treatment-naive ADHD • Dose: – 1.2-1.8 mg/kg/day – 45 ±21mg/day – Side effects: decreased appetite, abdominal pain – No treatment related serious adverse events
A t o m o x e t i n e & Pa r e n t Tr a i n i n g
Week Week
Group ADHD response Non-compliance Response
ATX 47% 44% 0.003 [ES 0.64]
ATX+PT 45% 23% 0.03 [ES 0.47]
ADHD Response Rate:
ATX > PBO [p=0.015] PT+PBO 29% 39% 0.06
ATX+PT ATX [p=NS] PBO 19% 16%A t o m o x e t i n e & Pa r e n t Tr a i n i n g 24-week extension phase • 60% of RCT phase responders continued to meet criteria for ADHD • Among ADHD responders: – ATX+PT 53% v ATX 23% • Among noncompliance responders: – PT+ATX 58% v ATX 14%
Gu a n f a c i n e ER
8-week RCT in ASD Youth with Hyperactivity
Autistic Disorder + Sign. Hyperactivity 62
(ABC-Hyperactivity score ≥24 + CGI-S ≥4)
Mean Age [Range] 8.5 ±2.3 [5–14]
Male 86%
Drug-naive 55%
Dose 3 mg/day [1 - 4]
3/19/21N ASD
ist and ADHD Rating Scale at Baseline and Endpoint (Week 8)
0) Placebo (N=32)
Guanfacine ER - Efficacy
-Squares Meana Raw Mean Least-Squares Meana
Effect
int 95% CI Baseline 95% CI Endpoint 95% CI p Sizeb
15.33–23.22 34.25 31.74–36.76 29.7 25.82–33.53 ,0.0001 1.67
10.01–17.06 18.06 14.54–21.58 16.1 12.68–19.54 0.20 0.27
8 7.26–12.27 12.06 8.71–15.41 8.6 6.10–11.02 0.41 0.13
6 2.03–5.26 9.31 7.31–11.32 5.9 4.37–7.49 0.02 0.41
ADHD Rating Scale - ADHD Rating Scale -
3.24–5.26 6.84 5.63–8.06 5.99 4.50–6.97 0.004 0.50
6
12.55–16.78
8.50–12.75
20.41
19.50
18.75–22.06
17.71–21.29
Inattention
19.5
18.7
17.52–21.56 0.0001
16.6–20.69 ,0.0001
1.17
1.72
Hyperactivity
21.44–29.03 39.91 37.50–42.32 38.0 34.4–41.63 ,0.0001 2.03
30
ity subscale were within 1 standard deviation of the population mean; the least-squares mean values at 30
e least-squares means at endpoint and dividing by the pooled standard deviation at baseline.
peractivity subscale were nearly 2 standard deviations above the population mean for developmentally
20 20
were no group or aggressive, and his speech was normal in tone and tempo.
riance models P=0.0001; ES 1.17
During the entire episode, there was no change in his sleep. PPBO [9.4%]
Placebo
with parent- Guanfacine
ABC Hyperactivity Least Square Means
se events are 40
this table were
blished before Significant improvement in:
[⇊ 13%]
• Repetitive behaviors(ABC-Stereotypy)
30
Event Review
the preferred
p PBO[25%])*
0 2 4 6 8
ild psychiatric Week
he was hyper- a
Higher scores reflect greater hyperactivity. ABC= Aberrant Behavior
as not agitated Checklist.
ajp in AdvanceGuanfacine ER – Efficacy
PBO GXR
• Dose-limiting AEs 5/32 9/30
[d/t emotional lability/drowsiness] [16%] [30%]
• Treatment-limiting AEs None 2 - Agitation[N=1]
- Drowsiness[N=1]
• Serious AEs None 1 (agitation @ 2mg/d)
Common AEs* PBO GXR p-value
Drowsiness 9% 87%Alpha-2 Adrenergic Agonist: Clonidine
Delivery Oral Clonidine Transdermal Clonidine
(Jaselkis, et al. 1992) (Frankhauser, et al. 1992)
6-week double-blind, cross-over 4-week, double-blind, cross-over
clonidine PO 4-10 mcg/kg/d clonidine TTD 3.5 mcg/kg/d
Methods n=8 males, 5-13yo (8 ±3 yrs.) with ASD n=9 males (~13 yrs.) with ASD +
+ hyperactivity (prior hx. of poor hyperarousal symptoms (including
response) hyperactivity)
Parent-teacher ratings: Superior to PBO
in reducing Hyperactivity No effect on ADHD symptoms per
Efficacy No significant separation from PBO on parent ratings
any of the clinician rated scales
Drowsiness Sedation
Tolerability Hypotension
FatigueIn Summary…..
ADHD Response in ASD Youth
• Methylphenidate & Atomoxetine.
- Response in patients HF-ASD is similar to observed with ADHD
- Adverse effects more frequent than typically expected may point
to missed comorbidities
- Improves affect regulation & joint attention
- Response rate & magnitude in patients with low IQ is less than
expected
• Guanfacine ER. Response similar to observed in children with ADHD
• Clonidine. Poorly tolerated
Consider using clinical scales for monitoring treatment effect
ADHD checklists, ECG, labs, etc.The Alan and Lorraine Bressler
Clinical and Research Program for Autism Spectrum
Disorders
M a s s a c h u s e t t s G e n e r a l H o s p i t a l , Boston MA
Sheeba A. Anteraper, PhD Yvonne Woodworth, BA
Joseph Biederman, MD
Kaustubh R. Patil, PhD Daniel Kaufman, BS
Janet Wozniak, MD
Stephen Faraone, PhD Alison Greene, BA
Gagan Joshi, MD
Ronna Fried, EdD Nina Dallenbach, BA
Lynn Grush, MD
Maribel Galdo, LCSW Emmaline Cook, BA
Amy Yule, MD
Maura Fitzgerald, MA Cecilia Law, BA
Carrie Vaudreuil, MD
Alissa Charles, BA
Robert Doyle, MD
aceranoglu@mgh.harvard.edu
(617) 726-7899 MGHASDprogram@Partners.org Facebook.com/BresslerMGH
http://www.massgeneral.org/psychiatry/services/autism_conditions.aspxYou can also read
