Twenty-two percent of U.S. doctors prescribing initial treatment for children with a new diagnosis of anxiety or depression during a recent six-year period chose medications that are not federally approved for use in children or were inconsistent with guidelines issued by professional associations, exposing patients to a greater risk of bad outcomes, according to a new Yale study.
When doctors deviate from guidelines in their initial treatments, the study showed, their adolescent patients have a higher probability of self-harm, are more likely to visit the emergency room, and have higher cumulative medical costs after two years compared with adolescent patients who were initially treated more appropriately.
The study, by Yale economist Jane Currie and Emily Cuddy of Duke University, was based on an analysis of health insurance claims from a large national insurer.
"Doctors have a very limited menu of federally approved drugs for treating mental illness in children, which can lead them to so-called off-label prescribing," said Currie, the David Swensen Professor of Economics in Yale's Faculty of Arts and Sciences. "We found that children have better outcomes when their physicians stick to FDA-approved treatments or off-label treatments recommended by professional associations.
"Our work suggests that analyses of large-scale insurance claims data can be helpful in identifying best practices for treating mental illness in adolescents."
The study is published in the Journal of Political Economy. Currie, who joined Yale's faculty in July 2025, conducted the research while a professor at Princeton University.
Physicians have wide discretion in caring for their patients, including the option to prescribe drugs and other treatments that are not approved by the U.S. Food and Drug Administration (FDA) or recommended in guidelines issued by either the FDA or professional societies.
One reason the FDA has approved only a handful of drugs for treating mental illness in children is that drug companies have little incentive to pursue costly pediatric clinical trials once medications have been approved for adults, since doctors can prescribe them off-label to children, the researchers explained. Professional guidelines expand the menu of available treatments by recommending options for off-label prescribing and treatments.
For the study, Currie and co-author Emily Cuddy of Duke University analyzed insurance claims data for 2012 to 2018 covering more than 45,000 children aged between the ages of 10 and 17 nationwide who were being treated for anxiety, depression, or adjustment disorders that feature those conditions. The data used in the study was anonymous, ensuring that patients' privacy was protected, Currie noted.
The researchers examined the effects of initial treatments after two years, dividing treatments into three groups: those that involved a drug that was FDA-approved for use in children; those that were not FDA approved but were consistent with asking professional guidelines; and those that were neither FDA approved nor consistent with guidelines, which they call "red-flag" prescribing.
They found that 22% of clinicians in the sample engaged in red-flag prescribing, while another 22% prescribed only FDA-approved medications and 55% stuck to medications that were not FDA-approved but were consistent with guidelines for treating mental illness in children issued by professional associations, such as the American Academy of pediatrics.
According to their analysis, more than 33% of children prescribed red-flag drugs had to visit a medical facility over the following two years compared to about 27% of children prescribed FDA-approved drugs and about 19% of children whose doctors followed professional guidelines.
Probability of self-harm was 5.7% for children who received red-flag treatments, 4.9% in the group treated with off-label medications recommended in professional guidelines, and 3.8% in the group treated with FDA-approved drugs, according to the study.
The study showed that average medical costs over two years were $1,745 for patients whose doctors prescribed off-label using professional guidelines, which was much lower than either the $9,557 for children prescribed red-flag drugs, or the $9,656 for those prescribed FDA-approved drugs.
"The good news is that a large majority of doctors are following professional guidelines or prescribing FDA-approved treatments, but a sizeable minority do engage in red-flag prescribing" Currie said. "It's a difficult situation for parents, who might want to familiarize themselves with the guidelines or, if possible, request a second opinion if they're unsure about the course of treatment that their child's doctor has prescribed."
