Weighing the risks of mental health drugs for children

Researchers try to fill gaps on whether mental health drugs are safe for children

By Alyssa Bindman

It is not just transplant patients tapering off anti-rejection drugs who use medications in traditionally untested ways. WHYY’s health and science intern and University of Pennsylvania Bioethics graduate student, Alyssa Bindman, examines the issue.

Children often receive prescriptions for medications to treat conditions such as schizophrenia and bipolar disorder that have been tested only on adults, leaving a lot of room for questions about the short and long-term effects of using them.

Additional Resources:

Practical and Ethical Issues in Pediatric Clinical Trials

CHOP’s “Parents’ Guide to Research”

Children and Clinical Studies, resources from the National Institutes for Health:

Food and Drug Administration, Ethical Issues

Resources about clinical trials & ethics:

NIH Ethics & Clinical Trials resource list (includes several links to websites related to clinical trials & ethics)

The Ethics of Clinical Research, Stanford Encyclopedia of Philosophy

Bioethics Forum: Ten Years Later: Jesse Gelsinger’s Death and Human Subjects Protection

“Children are not just small adults. They have different bodies, minds and brains. They undergo an enormous degree of development,” said Christoph Correll, a research psychiatrist at The Zucker Hillside Hospital and an associate professor of psychiatry at Yeshiva University’s Albert Einstein College of Medicine.

Clinical trials on children are notoriously challenging to conduct – and therefore scarce — in part because they are subject to high levels of scrutiny by review boards. The hesitance of some families to participate in studies out of fear or stress may create an additional barrier, Correll said. Some families and patients are overwhelmed and “don’t want to add any other iota of burden,” he said. They may be suspicious of research, feel exploited, or concerned their child will be used as a “guinea pig.”

Correll and a team of researchers at Zucker Hospital are trying to understand how certain medications work in children’s unique bodies. They were able to get over the hurdles of an experimental trial by simply tracking the outcomes of medications that were already being prescribed to children. They published their results in the Journal of the American Medical Association last fall showing that first-time use of anti-psychotics resulted in significant weight gain for children and adolescents when given any of the four most commonly prescribed drugs for behavioral, mood or psychosis-related problems over a three-month span. Of the 272 subjects, ages four to 19, the average weight gain was 10 to 19 pounds.

“The results are concerning because they include fat mass and waist circumference, which are associated with the metabolic syndrome in adults treated with antipsychotic medications and heart disease and in the general population,” the researchers wrote.

“Clinicians find themselves between a rock and a hard place in that they are trying to alleviate often severe and disabling psychiatric symptoms, yet the used medications are also not free of risks,” -Christoph Correll. The study is the largest of its kind to date that shows the effects of these drugs on children’s weight and metabolic abnormalities. The impact on weight is important to consider because obesity early in life puts children at risk for diabetes and early death. The four medications studied showed unequal increases in weight gain and blood sugar and fat levels, which may be important information for clinicians and families assessing risks and benefits for a particular patient.

Given the results of the study, Christopher Varley and Jon McClellan of Seattle Children’s Hospital recommended a reevaluation of the use of anti-psychotics in children. They wrote in an accompanying editorial to the study, “Given the risk for weight gain and long-term risk for cardiovascular and metabolic problems, the widespread and increasing use of atypical antipsychotic medications in children and adolescents should be reconsidered.”

Across the country, several other researchers are working to answer if anti-psychotic drugs to treat pediatric psychotic, mood, or aggressive disorders, such as risperidone and olanzapine, are safe and effective, and to determine proper dosage. For example, John Newcomer is leading an ongoing study looking at metabolic effects on more than 200 pediatric patients at Washington University in St. Louis. Robert L. Findling at Case Western Reserve University has researched how these drugs work in children in order to establish treatment guidelines.

For doctors, information to guide clinical practice cannot come soon enough. “A lot of anti-psychotics have been widely overused, but without clinical trials there won’t be information saying, when do they work? How well do they work? When there is no information, then every single child is a study,” said Mark Schriener, a pediatric anesthesiologist and associate professor of pediatrics at the University of Pennsylvania. Schreiner is also chair of the institutional review board for research at the Children’s Hospital of Philadelphia, which establishes ethical guidelines for research at the hospital, including studies involving anti-psychotics.

“Clinicians find themselves between a rock and a hard place in that they are trying to alleviate often severe and disabling psychiatric symptoms, yet the used medications are also not free of risks,” said Correll.

In the future, Correll urged more long-term safety studies, for six months and longer, to assess the true side effects of anti-psychotics on children. He recommended that doctors and family evaluate the risks and benefits of each treatment option, and determine if alternative, non-pharmaceutical options such as counseling and behavioral therapy can be applied. Once the drugs are prescribed, doctors may more carefully monitor of side effects, including tracking weight gain and blood sugar and fat levels.