Weight and leptin changes among risperidone-treated youths with autism: 6 month prospective data

Martin A et al. on behalf of the Research Units on Pediatric Psychopharmacology Autism Network

American Journal of Psychiatry 2004; 161(6): 1125-1127

Question: Is the weight gain seen in children with autism who are treated with risperidone related to changes in leptin levels?

Background: Children with autism treated with risperidone and other new generation antipsychotic medications usually experience some weight gain during the course of their treatment. The weight gain in some of these children and adolescents has been substantial and there are concerns about associated health risks. Obesity in children can be associated with higher blood pressure, and may increase the risk of diabetes, although these have not been specifically studied in children with risperidone related weight gain. Scientists are trying to understand why this weight gain occurs.

This study looked at the data used to determine if weight gain in children with autism who are treated with risperidone was greater than what would be expected for their age and growth. It also looked at whether or not leptin, a hormone produced by fat cells that has an effect on appetite and is associated with excessive weight gain, is responsible for the weight gain in the group under study. Weight gain in adults taking risperidone is known to be associated with disordered leptin levels.

Design: A prospective follow-up study.

Setting: University medical centres at Indiana University, Ohio State University, UCLA, Yale University, and Johns Hopkins University, all part of the Research Units on Pediatric Psychopharmacology Autism Network (RUPP Autism Network).

Participants: Children with autism aged 5 to 17 with serious aggression, agitation, or self-injurious behaviour who were treated with risperidone over the course of 6 months.

Main Outcome Measures: Blood tests measuring leptin levels were done at the beginning of the study, at 2 months into the study, and again at 6 months. The weight gain in the children treated with risperidone was compared to data for average normal weight gain in the general population of children of the same age group.

Main Results: Of the 101 children who entered the trial of risperidone, 63 completed 6 months on the drug. The weight gain seen in the children under study was found to be excessive compared to the expected change in weight resulting from normal growth. There was a lot of variability in the weight gained (the range was - 4.0 to 15.3 kg, with a mean of 5.6 kg) and weight gain seemed to be faster in the first 2 months of treatment. Of the 63 children, there were results of all 3 blood tests for leptin available for 45 of them. The leptin levels measured in their blood were not different from the control group members, and the leptin level at baseline did not predict the subsequent gain in weight. The most interesting finding was that those children who gained the most weight in the first month on the drug were those who also showed continued weight gain during the 6-month period. There was no association between the amount of weight gained and the participants’ age, gender, or racial background or the drug dose they were given.

Conclusion: This study looked at weight gain in children and adolescents with autism who were treated with risperidone and at their leptin levels during the study period. As a group, the patients increased their weight, but the amount of weight gained varied amongst the patients. Leptin levels in the blood were not associated with the weight gain, as they are in adults treated with new generation antipsychotic drugs. Thus, the mechanism for the weight gain continues to be unknown. The authors suggest that it is possible that rather than there being an increase in leptin levels during treatment with risperidone, the appetite centre in the brain does not detect the leptin given off by the fat cells. If this is the case, the brain does not signal the child to stop eating, thus leading to the weight gain. However, the important result of this study is that it provides confirmation that there is excessive weight gain in the population under study.

The fact that later weight gain is predicted by the weight gain during the first month on the drug provides clinicians and parents the opportunity to decide if a change of therapy would be better, or if vigorous exercise and dieting would be beneficial. Obesity in children is not benign. One complication is sleep apnea, a condition in which there is interrupted breathing during sleep. Sleep apnea can lead to daytime sleepiness, irritability, and worsening of inattention. There is increased likelihood of developing diabetes, high blood pressure, gall bladder disease and raised cholesterol. Obesity in adolescents also raises the risk of heart disease in adulthood.