Weight Gain and Metabolic Consequences of Risperidone in Young Children With Autism Spectrum Disorder

Abstract

Objective: We examine weight gain and metabolic consequences of risperidone monotherapy in children with autism spectrum disorder (ASD).

Method: This was a 24-week, multisite, randomized trial of risperidone only versus risperidone plus parent training in 124 children (mean age 6.9 ± 2.35 years; 105 boys and 19 girls) with ASD and serious behavioral problems. We monitored height, weight, waist circumference, and adverse effects during the trial. Fasting blood samples were obtained before treatment and at week 16.

Results: In 97 children with a mean of 22.9 ± 2.8 weeks of risperidone exposure, there was a 5.4 ± 3.4 kg weight gain over 24 weeks (p < .0001); waist circumference increased from 60.7 ± 10.4 cm to 66.8 ± 11.3 cm (p < .0001). At baseline, 59 of 97 children (60.8%) were classified as having normal weight; by week 24, only 25 of 85 (29.4%) remained in that group. Growth curve analysis showed a significant change in body mass index (BMI) z scores from pretreatment to week 24 (p < .0001). This effect was significantly greater for children with reported increased appetite in the first 8 weeks. From before treatment to week 16, there were significant increases in glucose (p = .02), hemoglobin A1c (p = .01), insulin (p <.0001), homeostatic model assessment-insulin resistance (HOMA-IR; p < .001), alanine aminotransferase (p = .01), and leptin (p < .0001). Adiponectin declined (p = .003). At baseline, 7 children met conventional criteria for metabolic syndrome; by week 16, 12 additional children were so classified.

Conclusion: Rapid weight gain with risperidone treatment may promote the cascade of biochemical indices associated with insulin resistance and metabolic syndrome. Appetite, weight, waist circumference, liver function tests, blood lipids, and glucose warrant monitoring. Clinical trial registration information-Drug and Behavioral Therapy for Children With Pervasive Developmental Disorders; http://clinicaltrials.gov/; NCT00080145.

Keywords: autism spectrum disorder; insulin resistance; metabolic syndrome; risperidone; weight gain.

Figure 1

Change in age and gender-adjusted weight categories across time. Note: Centers for Disease Control and prevention body mass index (BMI) reference ranges: Normal ≤ 85^th percentile; Overweight ≥ 85^th percentile to < 95^th percentile; Obese ≥ 95^th percentile. n=97 at baseline; 94 at Week 8; 95 at Week 16; 85 at Week 24. Of 59 participants with normal weight at baseline, 24 remained in normal weight at endpoint, 21 became overweight, 7 became obese; 7 were missing at Week 24. Of the 20 participants overweight at baseline, 1 was in normal weight; 3 remained overweight, 14 became obese; 2 were missing at Week 24. Of the 18 participants obese at baseline, 1 was overweight and 14 remained obese, 3 were missing.

Figure 2

A. Predictive growth curve of body mass index (BMI) z-score with 95% CI from mixed effect model with autoregressive correlation matrix on age–gender-adjusted BMI z-scores from 2000 Centers for Disease Control and Prevention (CDC) growth charts and CDC SAS code (http://www.cdc.gov/nccdphp/dnpao/growthcharts/resources/gc-calculate-BIV.sas). Note: The differences in BMI z-score from baseline are 0.71 (95% CI=[0.605, 0.808], p<.0001) and 0.74 (95% CI=[0.613, 0.866], p<.0001) at Weeks 16 and 24, respectively. B. Predicted growth curves of BMI z-score for participants with reported increase in appetite in the first 8 weeks (n=75) compared to those with no reported change in appetite (n=22). C. Predictive growth curves in children ≥ 7 years (n=49) and < 7 years (n=48).