Infectious Diseases

February 24, 2022

Study to explore neurologic impact of flu treatment

A Vanderbilt study will explore the neurologic and psychiatric complications of flu and evaluate adverse effects of the antiviral treatment oseltamivir, also known by the brand name Tamiflu.

For more than a decade, a rare side effect reported by patients with influenza has puzzled clinicians and researchers.

In some cases, patients with flu have experienced neuropsychiatric symptoms, such as behavior changes, hallucinations and even attempted suicide. The question: Are these neurologic or psychiatric complications due to the infection or are they related to the anti-viral medication used to treat the infection?

James Antoon, MD, PhD

Studies attempting to characterize the complications have had conflicting results.

James Antoon, MD, PhD, assistant professor of Pediatrics in the Division of Pediatric Hospital Medicine at Monroe Carell Jr. Children’s Hospital at Vanderbilt, recently received a career development award from the National Institute of Allergy and Infectious Diseases (NIAID) to research neurologic and psychiatric complications of flu and evaluate adverse effects of the antiviral treatment oseltamivir, also known by the brand name Tamiflu.

The K23 Mentored Patient Oriented Research Career Development Award provides $740,000 over four years and will assist Antoon in further studying the role of drug-drug interactions in the development of serious adverse events in children including seizures, meningitis, psychosis and suicidal ideation.

“This funding will go a long way in helping to answer the overriding question of whether Tamiflu causes these events or if they are complications from an underlying influenza infection,” Antoon said.

“Our team will conduct a population-based assessment of the neuropsychiatric events associated with influenza and will rigorously evaluate whether treatment with Tamiflu increases or decreases these events.”

While these neuropsychiatric events have also been reported in adults, the study will explore the impact on children.

Using a large database of children enrolled in Tennessee Medicaid, the group of investigators will identify children ages 5-18 with influenza and examine whether they experience neuropsychiatric events over a period of five influenza seasons, from 2015-2020.

“The Tenncare database is a rich source of information that can overcome the limited scope of previous studies,” said Antoon. “In preparation for this project, we have developed a validated method to accurately identify children hospitalized with a new neuropsychiatric event. During the project, we will determine if there are factors like genetics, underlying conditions or concurrent medications that may impact whether these events occur in children.”

The team will determine how often children with flu have these rare events, how often these events involve children who received Tamiflu and, finally, will examine other factors like drug-drug interactions that may increase or decrease the risk of these events in children taking Tamiflu.

Antoon’s research mentors include Carlos Grijalva, MD, MPH, professor of Health Policy and Biomedical Informatics, and Derek Williams, MD, associate professor of Pediatrics and chief of the Division of Pediatric Hospital Medicine. Additional collaborators and advisers include William Cooper, MD, MPH, vice president for Patient and Professional Advocacy at VUMC; Kathryn Edwards, MD, Sarah H. Sell and Cornelius Vanderbilt Chair in Pediatrics; Sara Van Driest, MD, PhD, associate professor of Pediatrics and Medicine, and Sunil Kripalani, MD, MSc, professor of Medicine and director of the Center for Health Services Research and the Center for Clinical Quality and Implementation Research at VUMC.

“It is an honor to receive this award to evaluate these serious events that may have a lifelong impact on a child’s life,” said Antoon. “Research supported by the NIAID has improved the health of millions around the globe. I hope that shedding light on these serious adverse events will allow us to expand our understanding of the role of both viruses, such as influenza, and their treatments in the development of these neuropsychiatric events.”