Risperidone 1994

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Risperidone 1994

APNA 25th Annual Conference
October 20, 2011 - Session 2014
Cardiometabolic
Side Effects of
Risperidone
in Children with
Autism
Susan J. Boorin, MSN, PMHNP-BC
PhD Candidate
Yale School of Nursing
1
This speaker has no conflicts of interest to disclose.
2
Boorin
1
Promise of Atypical Antipsychotic Medications
•
•
•
•
•
•
Clozapine – 1958* Risperidone – 1994
Risperidone Olanzapine – 1996
Quetiapine – 1997
Ziprasidone – 2001 Aripiprazole‐ 2001 Aripiprazole
2001
Dramatic ↑
Dramatic
↑ in in
antipsychotic use in the pediatric population * Not released in US until 1990
3
Proportion Outpatient Visits for Children diagnosed with an autism spectrum disorder and prescribed a psychotropic
Significant Increase in Psychotropics Prescribed 79%
80%
60%
39%
40%
20%
0%
1996‐2000
2001‐2005
psychotropic prescribed (Tobias, Chavez, Olfson & Crystal, 2009) Boorin
4
2
Atypical Antipsychotics
•
•
•
•
•
•
Clozapine – 1958* Risperidone – 1994
Risperidone Olanzapine – 1996
Quetiapine – 1997
Ziprasidone – 2001 Aripiprazole‐ 2001 Aripiprazole
2001
Report Card
 ↓ Motor Adverse Effects
 Benefit for negative symptoms
less clear
 Metabolic problems emerging as
major health concern
* Not released in US until 1990
5
RUPP Autism Network:
Risperidone only vs.
Risperidone + Parent Training
RUPP Autism Network, JAm Acad Child Adoles Psychiatry, 2009
6
Boorin
3
Baseline Demographics  Male: 85%
 75% White / 14% African American / 7% Hispanic / 3% Asian / Other 1%  65% Autistic Disorder, 30% PDD‐NOS, 6% Asperger’s 65% Autistic Disorder 30% PDD NOS 6% Asperger’s
N = 124
Age of sample: Mean age= 6.9 years, SD 2.4, range 4 to 13 years Mean Age: 6.9 years
50% 4‐6 years old 7
Medication Target Symptoms: Tantrums, Self‐Injury, Aggression, Irritability 35
Rapid Decrease in Mean Irritability Score 30
Irritability Score 25
20
Irritability Score 15
10
5
0
0
2
4
6
8
12
16
20
24
Week of Clinical Trial 8
Boorin
4
Weight Gain 9
Associated Behavioral Factors 70
Acctual Score (number) 60
Appetite Week 12‐24 pp
(mean) 50
Adaptive Communication (mean)
40
Adaptive Functioning Daily Living Skills (mean) 30
20
Impairment in Social Interaction: Autism Sx (mean)
10
0
< 15% weightgain Boorin
≥ 15% weightgain 10
5
Mild and Moderate Excessive Appetite 100
Percent Children 80
60
Excessive Appetite at Baseline No Report of Excessive Appetite at Baseline 40
20
24
20
16
8
12
7
6
5
4
3
2
1
Baseline 0
WEEKS
11
Does rapid weight gain carry risk independent of weight status? Excessive Weight Gain Group at Week 16 BMI < 1.645 Not Obese BMI ≥ 1.645 Obese 12
Boorin
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BMI Categories Adjusted for Age and Gender 70
60
Percen
nt 50
40
30
20
10
0
Baseline Week 8 W k8
Week 24 Target BMI
Overweight Obese Baseline 61
20
19
Week 8 44
22
34
Week 24 30
28
42
13
Adiposity: Bogalusa Heart Study
Webber et al, (1995). Obesity studies in Bogalusa. The American Journal of Medical Sciences* • Long‐term epidemiological study over a period of 20 years
•Examined cardiovascular risk factors in children, adolescents and young adults •Biracial population Sebastian Kaulitzki
b
l k | Dreamstime.com
|
•Clustering of childhood obesity with:
Blood pressure
Serum lipids
A predictor for adult obesity
*One of many articles using this dataset Boorin
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7
Calorie consumption /inactivity Lipocentric Framework Obesityy
Ectopic Free fatty acid pancreatic islets liver heart skeletal muscle 15
Relationship between BMI and Body fat:
Pediatric Rosetta Project
N = 1196
Age: 5‐18 year olds DEXA‐estimated body fatness • BMI for age < 85th
• BMI for age 85th to 94th percentile (n=200)*
• BMI for age ≥ 95th percentile * 20% of the children had body fatness comparable to those with higher BMIs, 30% had body fatness comparable with children with BMIs < 85th
percentile
(Freedman & Sherry, 2009,Pediatrics )
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Boorin
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Can you see risk?
• This girl is 4 years old and weighs 38.6 lbs
• Height = 39.2 inches http://www.cdc.gov/growthcharts/
Photo from UC Berkeley Longitudinal Study, 1973
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Plotted BMI – For – Age BMI
BMI
Girls: 2 to 20 years
BMI
BMI
18
http://www.cdc.gov/growthcharts/
Boorin
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Insulin Resistance (Kahn, Hull & Utzschneider (2006) Nature )
Insulin Resistance/Obesity
Increased
β‐cell function Impaired β‐cell function Compensatory Hyperinsulinemia Impaired Glucose Tolerance © Alila07 | Dreamstime.com
Normal glucose tolerance 19
Insulin Resistance: Clinical Monitoring • HOMA‐IR • Normal age‐related changes • Partner with Primary Care or Endocrinology • Note: Fasting plasma glucose may be within normal range despite the presence of hyperinsulinemia 20
Boorin
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At‐ Risk Criteria: Lipids Pediatric Considerations October 20, 2011 - Session 2014
Children in Trial no.,(%)
Baseline
Week 16
LDL
≥ 75th percentile for age and gender ≥ 75
til f
d
d
25 (26%)
23 (27%)
HDL ≤ 10th percentile for age and gender 26 (21%)
30 (31%)
Triglyceride ≥ 75th percentile for age and gender 41 (37%)
44 (45%)
REFERENCE: PEDIATRIC TABLE of Age and Gender Adjusted Lipid Categories :
Daniels, S.R., Greer, F.R. & the Committee on Nutrition (2008). Lipid Screening and Cardiovascular Health in Childhood, Pediatrics, 122(1),198‐208
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Six year old boy
Cultural differences?
BMI : > 95th
percentile for age and gender
Waist/Height ratio > .5 (considered a risk factor) Fasting Glucose = 95 mg/dL
© Lucian Coman | Dreamstime.com
Triglyceride level in 25th percentile category for gender and age 22
Boorin
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Fatty Liver: relationship with childhood obesity
Healthy Liver Over‐accumulation of Fat in Liver
Large multiethnic group of obese youth: n= 392 Liver fat measured by MRI technology Markers: Increased visceral fat Alanine Aminotransferase (ALT)
Plasma triglycerides
Insulin resistance 23
(Burgert et al. (2009) The Journal of Clinical Endocrinology & Metabolism)
What other information would be valuable? •Five year old girl
•Began treatment with risperidone last October
October 2010 Fasting glucose = 77 mg/dL
Lab work returns this week:
October 2011
October 2011 Fasting glucose = 91 mg/dL
ALT = 40 Units/liter 24
Boorin
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Pediatric Blood Pressure National High Blood Pressure Education Program Working Group on Children and Adolescents (2005). The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure In Children and Adolescents. US Dept of Health and Human Services * • Normal BP in children = SBP and DBP that is < the 90th percentile for gender, age and height • Hypertension in children = average SBP or DBP yp
g
that is ≥ the 95th percentile for gender, age and height (noted on at least 3 different occasions) *Excellent reference 25
Change from baseline to Week 16 of TX Boorin
Insulin (n=87) ↑ p= .0086 Glucose (n=100) ↑ p= .0065 HOMA‐IR ↑
p<.0002
Leptin (n=90) ↑ p< .0001 Adiponectin (n=90) ↓ p= .0047 Triglycerides (n=96) ↑ p= .001 Waist Circumference ↑ p< .0001
ALT (liver enzyme) ↑ p= 0.0015
Diastolic BP ↓
p= 0.0153
Appetite ↑ OR= 5.02 26
13
ADA Consensus on Antipsychotic Drugs and Obesity and Diabetes: Monitoring Protocol for Adults*
Start
4
wks
8
wks
12
wks
P
Personal/family
l/f il Hx
H
X
Weight (BMI)
X
Waist
circumference
X
Blood pressure
Fasting glucose
X
X
X
X
Fasting lipid
profile
X
X
Qtrly.
12
mos.
5
yrs.
X
X
X
X
X
X
X
X
X
*More frequent assessments may be warranted based on clinical status
American Diabetic Association (2004) Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care, 27, 596 ‐601
27
Preliminary Pediatric Modifications/Suggestions History
Assess hx of excessive appetite, and potential for ↑ appetite
Weight g
Monitor BMI using CDC growth charts g
g
adjusted for gender and age at every visit Waist Circumference Not enough evidence, not recommended at present Blood pressure Use age and gender adjusted norms to screen for hypertension F i Glucose Fasting
Gl
High risk children
Hi
h i k hild
may need to be referred dt b
f
d
for further evaluation: collaborate with primary care Fasting Lipids Use age and gender adjusted norms Consider more frequent monitoring
for high risk children 28
Boorin
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The influence of location: Visceral and intramyocellular Adiposity
SUBJECTS : N=14 insulin‐sensitive adolescents paired with 14 insulin‐resistant adolescents matched for age, gender, and body insulin
resistant adolescents matched for age gender and body
composition. RESULTS: Insulin‐sensitive adolescents had ↓ intramyocellular fat stores (p=0.017) and ↓visceral lipid deposition (p=0.04) CONCLUSION: Location of lipid deposition may influence insulin sensitivity (Weiss et al, 2005 The Journal of Clinical Endocrinology & Metabolism) 29
Expert pediatric recommendation: Supports use of BMI in clinical setting August, G. et al (2010). Prevention and treatment of pediatric obesity: an endocrine society clinical practice guideline based on expert opinion. J Clin Endocrinol Metab., D
December 2008, 93(12) 4576‐4599. b 2008 93(12) 4576 4599
Barlow, S.E. (2007). Expert Committee Recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: Summary report. Pediatrics, 120,supplement 4. Daniels, S.R. (2009). The use of BMI in the clinical setting. Pediatrics, 124, S35‐41 Correll, C. (2008). Antipsychotic use in children and adolescents: minimizing adverse effects to maximize outcomes. J. Am. Acad. Child Adolesc. Psychiatry, 47 (1) 9‐20. 30
Boorin
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Risperidone 1994

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