Oseltamivir is a commonly recommended antiviral drug for influenza in both adults and children. Since 2006, the United States Food and Drug Administration (USFDA) has added a warning label to oseltamivir due to safety concerns related to neuropsychiatric events in pediatric patients during treatment. It was challenging to separate the effects of the drug from the underlying disease because influenza infections cause neurological or behavioural problems. The objective of the study is to assess the use of oseltamivir associated with the risk of severe neuropsychiatric events in children and adolescents.
The limitation of this observational study is the inclusion of occurrences up to four weeks after discontinuing oseltamivir and the absence of a validated outcome measure. Children and adolescents between 5 and 17 years old who were enrolled in Tennessee Medicaid from July 1, 2016, to June 30, 2020, were selected as a retrospective cohort. A strong longitudinal data source is required to determine population-based incidence, along with the efficacy and safety of medications.
The institutional review boards of the Tennessee Department of Health and Vanderbilt University Medical Center approved this study. Influenza exposure was defined as the period from the day of influenza diagnosis (day 0) through the following 9 days. The clear interval between the conclusion of oseltamivir medication and the anticipated resolution of influenza sickness is because influenza usually lasts for 7 to 10 days, while the standard oseltamivir treatment duration is at least 5 days.
Multivariable Poisson regression models at the individual level were used to estimate adjusted incidence rate ratios (aIRRs) with 95% confidence intervals (CI). Researchers excluded treatment episodes in which oseltamivir was not administered on the same day. The influenza diagnosis is used to address the possibility of incorrect classification of antiviral exposure. The primary outcome was hospitalization for a neuropsychiatric event, and it was identified by using a validated methodology.
The incidence rate ratios (IRRs) were calculated by using Poisson regression to consider relevant variables on a person-day basis. During 19,688,320 person-weeks of follow-up, the cohort study included 692,295 children; of these, 1230 cases were neuropsychiatric episodes, including 898 neurologic and 332 psychiatric. During the research period, fewer than 2% of these cases experienced more than two influenza episodes. Oseltamivir was given to 66.7% patients who previously experienced an influenza episode. When psychiatric and neurologic incidents were examined individually in secondary analyses, the treated influenza group had psychiatric events of 0.80 (95% CI 0.34 to 1.88) and neurologic events of 0.45 (95% CI 0.25 to 0.83).
Seizures frequently occurred during influenza exposure time, while mood disorders occurred in 20.8% and suicidal or self-harming behaviours in 14.5% cases during exposure periods. The measured E-value was 3.2, and the reported IRR and unmeasured confounders show association with both oseltamivir and major neuropsychiatric events.
When compared to untreated influenza, oseltamivir therapy was linked with a 50% reduction in the risk of hospitalization for severe neuropsychiatric events in this large cohort. These results highlighted the safety of oseltamivir in the pediatric group and avoided serious complications related to influenza.
Reference: Antoon JW, Williams DJ, Bruce J, Sekmen M, Zhu Y, Grijalva CG. Influenza with and without oseltamivir treatment and neuropsychiatric events among children and adolescents. JAMA Neurol. 2025. doi:10.1001/jamaneurol.2025.1995
