Metabolic Effects of Olanzapine in Children with Autistic Disorder

Background: Antipsychotics are the best-studied drugs for reducing symptoms in children with autistic disorder. A safety concern with antipsychotics is that administration can be associated with increase in metabolic parameters such as weight, body mass index (BMI), fasting glucose, and fasting lipids (triglycerides, total cholesterol, HDL, LDL). Increase in metabolic parameters has been associated with increased risk of cardiovascular disease and diabetes.

Objectives: This study examines the effect of olanzapine on metabolic parameters in a population of children with autism who participated in a clinical trial of olanzapine.  Methods: Patients were 33 children (25 males, 8 females), aged 3-11.9 years (mean, 6.58 ± 2), diagnosed with autistic disorder. The sample included 24 Caucasians, 8 African Americans, and one Asian. The study included a six-week randomized, double-blind, placebo-controlled phase, followed by a six-week open treatment phase. Responders at the end of the 6 week open treatment phase continued to receive open olanzapine for an additional 20 week (32 weeks total study drug exposure). Safety measures included weekly BMI and laboratory studies were obtained at baseline and week 12. Paired t-tests were performed comparing week 12 and baseline values to identify any significant olanzapine associated increases in BMI z-score, fasting glucose, and lipids. The CDC ¹ BMI criteria were used to categorize children as obese (≥95^th percentile for BMI), overweight (85^th ≤ x < 95^th percentile), healthy (5^th ≤ x < 85^th), and underweight (< 5^th percentile).
Results: At baseline, 70.3% of children were at a healthy weight, 21.6% were overweight, 2.7% were obese, and 5.4% were underweight. By week 12, 42.4% were healthy weight, 21.2% were overweight, and 36.4% were obese. Paired t-tests comparing the BMI z-score from baseline and week 12 showed a mean increase of 0.85 ± 0.5 which was significant (t = 9.8, df = 32, p = 0.0000). There was no clinically significant change in fasting glucose. There was also no systematic change in any of the fasting lipid parameters. For example, at baseline, six subjects had elevated triglycerides (TG), but by week 12, two of these subjects experienced normalization in their levels while four subjects with normal TG levels at baseline experienced an elevation. Overall, the mean increase for fasting triglycerides was 1.8 mg/dL which did not reach statistical significance. Mean total cholesterol increased by 3.8 mg/dL from baseline to week 12, not statistically or clinically significant. Mean changes in HDL and LDL were 0.2 mg/dL and 4.5 mg/dL, respectively; neither reached statistical or clinical significance.
Conclusions: The results of this study suggest olanzapine significantly increases BMI when administered to children with autism. Other clinically significant effects on metabolic parameters were not found in this twelve week study.

Reference:
1. www.cdc.gov