Cardiometabolic Consequences of Risperidone in Children with Autism Cardiometabolic Consequences of...
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Transcript of Cardiometabolic Consequences of Risperidone in Children with Autism Cardiometabolic Consequences of...
Cardiometabolic Consequences of
Risperidone in Children with
Autism
Susan J. Boorin, MSN, APRN-BC PhD Candidate, 2012
Yale University School of Nursing
Promise of Atypical Antipsychotic Medications
• Clozapine – 1958* • Risperidone – 1994• Olanzapine – 1996• Quetiapine – 1997• Ziprasidone – 2001 • Aripiprazole - 2001• Asenapine – 2009
* Not released in US until 1990
Pediatric antipsychotic use in US 1993-2002
Six-fold increase in antipsychotic use in office-based practice ( National Ambulatory Care Survey and US Census, Olfson et al, 2006) 92% of visits: atypical antipsychotic prescription, with risperidone most common
“Core symptoms” of Pervasive Developmental Disorders
Qualitative impairment in social interaction
Qualitative impairment in communication
Restrictive and stereotyped patterns of behavior and interests
Autistic Disorder + + +
Asperger’s Disorder + No evidence of a language delay
+
Pervasive developmental disorder not otherwise specified
+ Communication or Restrictive interests
*Aberrant Behavior Checklist subscale: Irritability
*Mean Score Changes
Risperidone versus placebo in children with autism and serious behavioral problems
N=101, Ages 5-17
RUPP Autism Network, 2002
Target Symptoms*: tantrums, aggression, self-injury, irritability
RUPP Autism Network:Risperidone only vs.
Risperidone + Parent Training
RUPP Autism Network, JAm Acad Child Adoles Psychiatry, 2009
All Children Treated with Risperidone
Design
124 subjects (Ages 4-13 years)
Diagnosis: a Pervasive Developmental Disorder (Autism
Spectrum Disorder)
6-month prospective study
Risperidone Only versus Risperidone + Parent Training
Baseline Demographics n = 124 Male: 85%
75% White / 14% African American / 7% Hispanic / 3% Asian / Other 1%
65% Autistic Disorder, 30% PDD-NOS, 6% Asperger’s
Median Age: 6.0 years
50% 4-6 years old
Median Weight Percentiles
Baseline Week 4 Week 8 Week 12 Week 16 Week 24 75
80
85
90
95
100
Weight Percentile
Weight Percentile
Absolute Weight Gain mean: 11.7 ± 7.3 lbs
range: – 2 to 36.4 lbs
Parent Report of Excessive Appetite
Base-line
Week 1
Week 2
Week 3
Week 4
Week 5
Week 6
Week 7
Week 8
Week 12
Week 16
Week 20
Week 24
0
10
20
30
40
50
60
70
Excessive Appetite
Baseline Week 8 Week 16 Week 24
Normal 60 41 32.4 26
Overweight 21 24.6 26.9 31.2
Obese 10 10.5 13.9 9.3
Severely Obese 9 23.7 26.9 33.3
5
15
25
35
45
55BMI Categories
Perc
ent
Chi
ldre
n
Change in metabolic indices from baseline to Week 16
Insulin (mean) (n=87) ↑ p = .0086
Glucose (mean) (n=100) ↑ p = .0065
Triglycerides
(mean) (n=96) ↑
> 90th percentile (standardized category) ↑
p = .001
p = 0.55
Selected Metabolic Indices Baseline to Week 16
Change in Adipocyte Hormones Baseline to Week 16
Adipocyte Tissue
Dreamstime
Adipocyte Hormones Baseline to Week 16
Leptin (n=90)mean (95% CL) ↑ p < .0001
Adiponectin (n=90) mean (95% CL) ↓ p < .0047
Waist : Height Ratio ≥ .5
Dreamstime
Visceral Fat
Central Adiposity
0
10
20
30
40
50
60
Baseline Week 24
Week 2460%
Central AdiposityWaist : Height ratio ≥ .5 ↑
Baseline31%
Weight Over Time
Weight gain ≥ 15% n = 46%
Base-line
Week4 Week8 Week12 Week 16
Week 20
Week 24
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
< 15% wt gain by week 16 15% + wt gain by week 16
TIME
Cha
nge
in W
eigh
t Z
-Sco
re
Change in Weight z-Score
Consequences of > 15% Weight Gain
Odds ratio (adjusted for baseline obesity) for adverse metabolic outcomes at Week 16
↑ LDL cholesterol
↑ Triglyceride Adiponectin ≤ 12.2
Central adiposity*
≥ 15% weight gain
2.7 [1.0 -7.5] 4.6 [1.7-12.7] 5.2 [1.3 – 21] 6.1 [2 – 18]
* Waist to height ratio ≥ 0.5
Clinical Implications
Consensus Statement, 2004
American Diabetes Association: Consensus development conference on antipsychotic drugs and obesity and diabetes (Consensus Statement). Diabetes Care 27:596–601, 2004
Pediatric Modifications/Suggestions
History •Assess history of excessive appetite
• Younger age-group
• Maternal obesity, history of type II diabetes
Weight •Monitor BMI at every visit (using CDC growth charts adjusted for gender and age)
Waist to Height Ratio Simple, but useful measure of central adiposity
Blood pressure Use age and gender adjusted norms to screen for hypertension
Fasting Lipids •Use age and gender adjusted norms
•More frequent monitoring for high risk children
Fasting Glucose •Important to Monitor
•Not an early marker for children
•Healthy children insulin to manage in glucose ….
Pediatric Modifications/Suggestions
Insulin Resistanceby HOMA-IR
Baseline Week 16
0
5
10
15
20
25
30
All Children
Per
cent
Chi
ldre
n
Insulin Resistance at Week 16 (By HOMA-IR; n = 21)
Insulin Resistance
Positive
21% glucose ≥ 100 mg/dL
38% at-risk triglyceride (≥ 90th percentile)
57% obese
In conclusion
Metabolic changes were significant Only prescribe risperidone after a careful
analysis of benefit and riskDue to early weight gain, healthy lifestyle
choices should be emphasized prior to starting the medication
Thank You