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