NEW ORLEANS — Worrisome and clinically measurable metabolic changes can be seen in just 12 weeks among children and adolescents who received antipsychotic medications in a National Institutes of Health–sponsored study, prompting serious concern among clinicians who learned of the results at the meeting.
The results struck at the heart of a troubling dichotomy: an explosion of prescriptions of antipsychotic medications for children, but little evidence in real-world practice that young patients are being routinely screened for metabolic changes that have the potential to shorten life expectancy.
The ongoing Metabolic Effects of Antipsychotics in Children study has already enrolled more than 140 children aged 7-18 years who were already slated to be placed on antipsychotics in the community.
Investigators closely monitored changes over 3 months in body fat using dual-energy x-ray absorptiometry (DXA) and insulin sensitivity using gold-standard methods, as well as tracking clinically available measures such as body mass index (BMI) percentile, and plasma glucose and lipids.
Body fat percentages rose in “not all, but certainly the majority of these children and youth,” said Dr. John W. Newcomer, professor of psychiatry and medicine and Director of the Center for Clinical Studies at Washington University in St. Louis.
Mean increases were highly variable among children and adolescents taking antipsychotic medications, but have averaged almost 3 kilos, or 6.5 pounds, “of body fat, not just weight,” in just 12 weeks, he said.
Some variance was seen in mean percent body fat accrual depending on which antipsychotic medication the children and adolescents received in the randomized open-label study, with olanzapine linked to a roughly 5% increase; aripiprazole, about a 1% increase; and risperidone falling somewhere in the middle at about 3%.
However, box plots revealed “substantial overlap” in the results, showing that each individual child's metabolic response to a given drug is somewhat unpredictable.
“You can find kids who take any one of these medications and potentially get a substantial increase in body fat, and you can also find kids who take any one of these agents who actually have very little change in body fat, although some medications are associated with a higher risk of substantial increase,” Dr. Newcomer said.
Increases in BMI percentiles were “substantial” as well, and closely paralleled more sophisticated measures of body fat, such as DXA.
“The good news is, it's pretty easy to track the changes in adiposity,” said Dr. Newcomer in an interview following the meeting.
“We used very fancy and expensive measures of body fat, but what pediatricians have in the front of every kid's chart (the BMI percentage table) does a darned good job of not only lining up where the child is at the baseline screen, but also in tracking changes over time.”
In a similar vein, the study found that simple blood cholesterol profiles—especially triglycerides and HDL—did a “halfway decent job” of estimating insulin sensitivity at baseline and then tracking changes through the early months of therapy, Dr. Newcomer added.
“The point is … don't wait a year to check the labs,” he said. “Don't not look.”
What is troubling to many is the fact that many clinicians indeed are not looking.
A Medicaid claims data study published earlier this year found that glucose screening was performed in just 31.6% and lipid testing in just 13.4% of 5,370 children aged 6-17 years prescribed antipsychotic drugs from July 1, 2004, to June 30, 2006 (Arch. Pediatr. Adolesc. Med. 2010;164:344-51).
Dr. Newcomer, a coauthor on the Medicaid claims research, said a growing number of “very eye-opening studies” about the enduring impact of childhood metabolic dysregulation and obesity should make clinicians weigh risks and consequences carefully when choosing drugs to prescribe for childhood schizophrenia, and perhaps even more so for use in disruptive behavior disorders and other nonpsychotic diagnoses.
“I have certainly learned that there are children at the end of the road of clinical options who are either not going to be in school or unable to participate without some heroic treatment measures, such as low-dose antipsychotic treatment, to help them to re-engage in education,” he said.
At the same time, relatively brief pharmacologic interventions for children who do not have schizophrenia or bipolar disorder should leave “a metabolic footprint … as modest as possible,” he said.
The Washington University study extended body weight findings from the nonrandomized SATIETY study published last year (JAMA 2009;302:1765-73), in which 272 4- to 19-year-olds prescribed antipsychotic drugs gained from a mean 4.4 kg (aripiprazole) to 8.5 kg (olanzapine) in a median of just 10.8 weeks on medication.