By Jessica Pasley
For decades, medical professionals debated whether a common antiviral medication used to treat influenza in children caused neuropsychiatric events or whether the infection itself was the culprit.
Now researchers at Monroe Carell Jr. Children’s Hospital at Vanderbilt, in Nashville, Tenn., have debunked a long-standing theory about oseltamivir. According to the study, oseltamivir treatment during flu episodes was associated with a reduced risk for serious neuropsychiatric events, such as seizures, altered mental status and hallucination (JAMA Neurol 2025 Aug 4. doi:10.1001/jamaneurol.2025.1995).
“Our findings demonstrated what many pediatricians have long suspected, that the flu, not the flu treatment, is associated with neuropsychiatric events,” said principal investigator James Antoon, MD, PhD, MPH, an assistant professor of pediatrics in the Division of Pediatric Hospital Medicine at Monroe Carell. “In fact, oseltamivir treatment seems to prevent neuropsychiatric events rather than cause them.”
The team reviewed the de-identified data from a cohort of children and adolescents 5 to 17 years of age who were enrolled in TennCare Medicaid between July 1, 2016, and June 30, 2020.
During the four-year period, 692,295 children, with a median age of 11 years, were included in the study cohort. During follow-up, the children experienced 1,230 serious neuropsychiatric events (898 neurologic and 332 psychiatric).
The clinical outcomes definition included both neurologic (seizures, encephalitis, altered mental status, ataxia/movement disorders, vision changes, dizziness, headache, sleeping disorders) and psychiatric (suicidal or self-harm behaviors, mood disorders, psychosis/hallucination) events.
Dr. James Antoon, an assistant professor of pediatrics in the Division of Pediatric Hospital Medicine at Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tenn.
They found the following:
- Influenza itself was associated with an increase in neuropsychiatric events compared with children with no influenza, regardless of oseltamivir use.
- Among children with influenza, those treated with oseltamivir had about a 50% reduction in neuropsychiatric events.
- Among children without influenza, those who were treated with oseltamivir prophylactically had the same rate of events as the baseline group with no influenza.
“Taken together, these three findings do not support the theory that oseltamivir increases the risk of neuropsychiatric events. It’s the influenza,” Dr. Antoon said.
“The 2024-2025 influenza season highlighted the severity of influenza-associated neurologic complications, with many centers reporting increased frequency and severity of neurologic events during the most recent season,” Dr. Antoon said. “It is important for patients and families to know the true risk–benefit profile of flu treatments, such as oseltamivir, that are recommended by the American Academy of Pediatrics.”
The investigators hope the findings will provide reassurance to caregivers and medical professionals about the safety of oseltamivir and its role in preventing flu-associated complications.
“These flu treatments are safe and effective, especially when used early in the course of clinical disease,” added senior author Carlos Grijalva, MD, MPH, a professor of health policy and biomedical informatics at Vanderbilt University Medical Center.
Because influenza can cause serious disease in children, especially those younger than 5 years of age, the CDC recommends that most children 6 months and older, as well as their caregivers, receive an annual flu shot.
The study was funded by the National Institutes of Health. The story first appeared on the Vanderbilt website. It has been edited for style.
