Observational study finds oseltamivir treatment reduces neuropsychiatric events in children — Evidence Review

A large study from the Monroe Carell Jr. Children's Hospital at Vanderbilt finds that oseltamivir (Tamiflu) use in children with influenza is not associated with increased risk of serious neuropsychiatric events; instead, treatment was linked to about a 50% reduction in such complications. Multiple previous studies generally support these findings, indicating that oseltamivir does not increase the risk of neuropsychiatric or central nervous system (CNS) events in children or adolescents.

• Several large-scale observational studies and reviews have consistently found no increase—and in some cases, a reduced risk—of neuropsychiatric events in children treated with oseltamivir, aligning with the new study’s results 2 3 5.
• Reports of neuropsychiatric events in influenza patients have more often been attributed to the infection itself rather than the antiviral treatment; this is further supported by case series documenting severe neurologic complications following influenza infection 3 6.
• While some early reports raised concerns about neuropsychiatric side effects, especially in pediatric patients, these were not substantiated by controlled studies, and randomized trials have demonstrated the general safety and tolerability of oseltamivir in children 7 8 9 11.

Study Overview and Key Findings

Concerns about oseltamivir’s neuropsychiatric safety in children have persisted for years, fueled by post-marketing reports and uncertainty over whether the drug or influenza itself caused adverse events such as seizures or hallucinations. This study is timely given the recent increase in reports of severe influenza-associated neurological complications in pediatric populations, particularly during the 2024-2025 influenza season. Importantly, the analysis leverages a very large, representative pediatric cohort and directly compares risk between those treated and untreated with oseltamivir, offering new clarity on a contentious safety issue.

Property	Value
Organization	Monroe Carell Jr. Children's Hospital at Vanderbilt, Vanderbilt University Medical Center
Journal Name	JAMA Neurology
Authors	James Antoon, Carlos Grijalva
Population	Children and adolescents ages 5-17
Sample Size	n=692,295
Methods	Observational Study
Outcome	Neuropsychiatric events, including seizures and hallucinations
Results	Oseltamivir treatment reduced neuropsychiatric events by roughly 50%.

Literature Review: Related Studies

To contextualize these findings, we searched the Consensus research paper database, which contains over 200 million scholarly articles. The following search queries were used to identify relevant literature:

1. oseltamivir neuropsychiatric events children
2. flu drug seizures treatment outcomes
3. oseltamivir safety profile pediatric patients

Topic	Key Findings
Does oseltamivir increase the risk of neuropsychiatric events in children?	- Multiple large observational studies and reviews found no increased risk of CNS or neuropsychiatric events in children treated with oseltamivir, and some reported a decreased risk compared to untreated influenza cases 2 3 5. - Randomized controlled trials and meta-analyses confirm a favorable safety profile, with neuropsychiatric events being rare and not significantly different from placebo 7 8 9 11.
What adverse effects are most commonly associated with oseltamivir in pediatric patients?	- Gastrointestinal side effects (vomiting, diarrhea) are the most frequently reported adverse events, while neuropsychiatric symptoms are infrequent, mild, and transient 1 8 10. - Adherence to oseltamivir may be affected by mild side effects, but serious adverse reactions are uncommon 1 8 10.
What is the relationship between influenza infection and neurologic complications?	- Influenza itself is associated with a spectrum of neurologic complications in children, including seizures and encephalitis, independent of antiviral treatment 3 6. - Early antiviral treatment may reduce the risk or severity of influenza-associated neurologic events 6 8.
Does oseltamivir increase the risk of suicidality or severe psychiatric events?	- Large database studies found no association between oseltamivir use and increased risk of suicide or severe psychiatric events in pediatric patients 4 5. - Case-crossover and propensity-matched analyses did not detect elevated risk of suicide or psychiatric hospitalizations with oseltamivir treatment 4 5.

Does oseltamivir increase the risk of neuropsychiatric events in children?

The majority of well-designed observational studies and systematic reviews indicate that oseltamivir does not increase the risk of neuropsychiatric or CNS events in pediatric populations. Several studies, including large healthcare claims analyses, have even observed a reduced risk of such events among children treated with oseltamivir compared to those untreated or receiving placebo. This aligns closely with the new Vanderbilt study, which also found a lower incidence of neuropsychiatric complications in treated children.

• Propensity-matched cohort studies reported decreased odds of CNS-related and neuropsychiatric events in oseltamivir-treated pediatric patients compared to untreated controls 2 3 5.
• Literature reviews found no plausible pharmacological mechanism linking oseltamivir to neuropsychiatric events and highlighted that the incidence rates are not elevated in treated patients 3.
• Randomized trials and meta-analyses consistently show rare occurrence of neuropsychiatric side effects without significant differences from placebo groups 7 8 9.
• The new study’s finding of a roughly 50% reduction in risk mirrors trends seen in these previous analyses 2 3 5.

What adverse effects are most commonly associated with oseltamivir in pediatric patients?

Across studies, gastrointestinal symptoms—particularly vomiting and diarrhea—are the most common adverse effects of oseltamivir in children. Neuropsychiatric symptoms, when present, are typically mild and transient, and their rates do not exceed those seen in placebo groups or in children with influenza who are not treated with antivirals.

• Survey-based and observational studies consistently report vomiting as the most frequent side effect, followed by diarrhea and occasional mild insomnia or ear disorders 1 8 10.
• Adherence to treatment can be compromised by these mild side effects, but serious adverse reactions are rare 1 8 10.
• Meta-analyses and randomized controlled trials confirm gastrointestinal events as the only significantly increased adverse outcome in treated children 8.
• The safety findings of the new Vanderbilt study are in line with these reports, showing no increased risk of serious psychiatric or neurologic side effects 8 10.

What is the relationship between influenza infection and neurologic complications?

Multiple studies emphasize that influenza infection itself, rather than oseltamivir treatment, is responsible for the majority of serious neurologic complications seen in pediatric patients. These include seizures, encephalitis, and other CNS manifestations, which can occur regardless of antiviral use.

• Case series and observational research have documented severe neurologic outcomes, such as encephalitis and seizures, directly linked to influenza infection 3 6.
• Early initiation of antiviral therapy, including oseltamivir, may mitigate the risk or severity of these complications 6 8.
• The Vanderbilt study directly supports this view, finding higher neuropsychiatric event rates in children with influenza irrespective of oseltamivir use, and a protective association with treatment.
• The distinction between infection-driven and drug-induced complications is a central theme across the literature 3 6 8.

Does oseltamivir increase the risk of suicidality or severe psychiatric events?

Concerns about a potential link between oseltamivir use and suicidality or severe psychiatric reactions in children have not been substantiated by large-scale analyses. Studies using rigorous case-crossover and matched cohort designs have found no significant association between oseltamivir exposure and increased risk of suicide, suicide attempts, or psychiatric hospitalizations.

• National claims database studies specifically addressed the risk of suicide and found no elevated risk associated with oseltamivir 4.
• The absolute risk of psychiatric events following oseltamivir treatment is very low and not significantly different from rates in untreated children 5.
• These findings reinforce the safety profile highlighted in the new Vanderbilt study and provide reassurance for clinicians and families 4 5.
• Monitoring and reporting continue, but current evidence supports the continued use of oseltamivir without heightened concern for suicidality or severe psychiatric events 4 5.

Future Research Questions

While the current study and related literature provide strong evidence for the safety of oseltamivir in pediatric populations, several questions remain. Future research is needed to address gaps such as long-term neurodevelopmental outcomes, the impact of oseltamivir in specific subpopulations, and the mechanisms underlying influenza-associated neurologic complications.

Research Question	Relevance
What are the long-term neurodevelopmental outcomes in children who experience influenza-associated neurologic complications?	Understanding long-term outcomes is critical for anticipating healthcare needs and guiding supportive interventions for affected children 6. Existing studies generally focus on acute outcomes rather than long-term follow-up.
Does early administration of oseltamivir further reduce the risk of neurologic complications in high-risk pediatric subpopulations?	The timing and effectiveness of antiviral therapy in high-risk groups, such as children with underlying neurological or immune conditions, require further study to optimize outcomes 6 8.
What biological mechanisms underlie influenza-associated neuropsychiatric complications in children?	The pathophysiology of influenza-associated CNS events remains poorly understood, and elucidating mechanisms could inform prevention and treatment strategies 3 6.
Are there genetic or environmental factors that predispose children to neuropsychiatric events with influenza or oseltamivir exposure?	Identifying risk factors could help tailor treatment and monitoring for susceptible individuals; previous reviews have not found clear genetic predispositions, but further research is warranted 3.
What is the impact of oseltamivir treatment on mild or subclinical neuropsychiatric symptoms in children with influenza?	Mild neuropsychiatric symptoms are often underreported, and understanding their frequency and significance could improve risk communication and patient care 1 10.