Flu virus triggers neuropsychiatric symptoms not the medication

For decades, medical professionals debated whether a common antiviral medication used to treat flu in children caused neuropsychiatric events or if the infection itself was the culprit.

Now researchers at Monroe Carell Jr. Children's Hospital at Vanderbilt have debunked a long-standing theory about oseltamivir, known as Tamiflu.

According to the study, published in JAMA Neurology, oseltamivir treatment during flu episodes was associated with a reduced risk of serious neuropsychiatric events, such as seizures, altered mental status and hallucination.

"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, 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."

Key points:

• Influenza itself was associated with an increase in neuropsychiatric events compared to children with no influenza, regardless of oseltamivir use.
• Among children with influenza, those treated with oseltamivir had about 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," said Antoon. "It's the influenza."

The team reviewed the de-identified data from a cohort of children and adolescents ages 5-17 who were enrolled in Tennessee 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, study 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.

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. 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."

James Antoon, MD, PhD, MPH, Assistant Professor of Pediatrics, Division of Pediatric Hospital Medicine, Monroe Carell

"These flu treatments are safe and effective, especially when used early in the course of clinical disease," added senior author Carlos Grijalva, MD, MPH, professor of Health Policy and Biomedical Informatics at Vanderbilt University Medical Center.

Investigators hope the findings will provide reassurance to both caregivers and medical professionals about the safety of oseltamivir and its role in preventing flu-associated complications.

The study was funded by the National Institutes of Health (grants K23AI168496, K24AI148459 and P50HD106446).