Tamiflu Found to Be Ineffective, May Increase Mortality in Patients Critically Ill With Influenza

A randomized clinical trial posted as a preprint on July 27, 2026, found that treatment with oseltamivir, commonly known by the brand name Tamiflu, is not only ineffective, but highly likely to increase 90-day mortality in critically ill patients with influenza. Researchers enrolled 442 critically ill patients aged 12 and older with laboratory-confirmed influenza between March 2020 and March 2026. Patients in the trial were randomly assigned to receive either five or 10 days of oseltamivir (Tamiflu), or no antiviral treatment to determine the drug’s efficacy in the critically ill, evidence the researchers said is lacking from previous randomized trials. The primary outcome, researchers said, “was 90-day mortality.”¹

Researchers used Bayesian statistical methods to estimate the probability that the drug increased the risk of death and found a 98.0 percent probability of harm with five days of Tamiflu and a 98.2 percent probability with the 10-day regimen. “Harm” in the study referred to an increased risk of 90-day mortality compared with receiving no antiviral treatment. Both treatment groups crossed the trial’s predetermined threshold for inferiority, meaning the results were so concerning that researchers stopped enrolling new participants in the oseltamivir treatment groups.²

More patients who received Tamiflu died within 90 days than patients who received no antiviral, and the statistical analysis indicated a very high probability that the drug increased mortality. Over 19 percent of participants who received Tamiflu (the five- and 10-day regimens, respectively) died, whereas only 13.7 percent of participants who received no Tamiflu died. As the study notes, “Treatment with oseltamivir is ineffective and highly likely to increase 90-day mortality in critically ill patients with influenza.”³

More than 25 Percent of Tamiflu Prescriptions Not Tied to Influenza Diagnoses

Tamiflu was first approved by the U.S. Food and Drug Administration (FDA) on Oct. 27, 1999 and, today, is the most widely used antiviral agent in the United States. A 2026 study found Tamiflu to be “the most prescribed antiviral during the 2016–2022 influenza seasons.” Although Tamiflu is FDA-approved to treat “acute, uncomplicated” influenza A or B,⁴ according to the study, more than 25 percent of influenza antiviral prescriptions examined were not associated with an influenza diagnosis.⁵

Testing for influenza is not required before antiviral drugs are prescribed, and Tamiflu is the only influenza antiviral recommended off label for hospitalized patients. As the study notes, “Testing is not required to prescribe influenza antiviral drugs and hence, healthcare providers can make clinical diagnoses based on symptoms.”⁶

Tamiflu Package Insert Warns of Neuropsychiatric Events Resulting in Fatal Outcomes

The Center for Infectious Disease Research and Policy (CIDRAP) reported in 2025 that Tamiflu has “carried a black-box warning for 20 years,” “suggesting that use in pediatric patients may be linked to neuropsychiatric events, including confusion, delirium, and abnormal behavior.”⁷ A black-box warning is the FDA’s most serious safety-related warning, intended to alert patients and providers of serious or life-threatening risks.

The current prescribing information for the drug, last revised in 2019, does not display a black-box warning, but does specify serious neuropsychiatric risks in section 5.2, stating, “There have been post-marketing reports of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving TAMIFLU.”⁸ The drug’s website further states, “People with the flu, particularly children and adolescents, may be at an increased risk of seizure, confusion, or abnormal behavior early during their illness.”⁹

Concerns About 2025 Study That Associated Tamiflu With Lower Risk of Serious Neuropsychiatric Events

A JAMA study published in 2025 aimed to determine the association between influenza, oseltamivir, and serious neuropsychiatric events among children and adolescents. The retrospective cohort study analyzed Tennessee Medicaid data rather than data from a randomized clinical trial. Vanderbilt University Medical Center (VUMC) said of the study, “Now researchers at Monroe Carell Jr. Children’s Hospital at Vanderbilt have debunked a long-standing theory about oseltamivir, known as Tamiflu,” referring to postmarketing psychiatric event reports that occurred in pediatric patients.¹⁰ The study found that it was influenza itself, not the drug, which was associated with an increased risk of serious neuropsychiatric events.¹¹

However, lead study author, James Antoon, MD, PhD, MPH, reported receiving personal fees for serving on an AstraZeneca Scientific Advisory Board during the conduct of the study. AstraZeneca is the manufacturer of FluMist, an influenza vaccine approved for the prevention of influenza. Senior author Carlos Grijalva, MD, MPH, also disclosed personal fees from GSK and Merck, and contracts with Syneos Health, the U.S. Centers for Disease Control and Prevention (CDC), and FDA outside the submitted work.¹²

Although VUMC implied the 2025 JAMA study exonerated Tamiflu, endorsing the findings that influenza, not the drug, caused the identified 1,230 neuropsychiatric events requiring hospitalization in the study, the researchers stated that they did not have laboratory test results confirming influenza, making it impossible to establish that influenza itself caused the events or that Tamiflu caused the observed reduction in risk. Influenza cases were instead identified using ICD-10 diagnosis codes. AS the study states, “Influenza cases were identified using outpatient International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes … as laboratory results are not available in the databases.”¹³

Tamiflu’s History Marked by Disputes Over Trial Data, Efficacy Concerns and Selective Reporting

Maryanne Demasi, PhD, writing for The Defender, discusses the drug’s checkered history, including allegations that Tamiflu drugmaker Roche cherry-picked clinical-trial data released, subsequent Cochrane reviews raising efficacy concerns, selective reporting, and publication bias.

“Tamiflu had never been properly tested, yet doctors had become so convinced it worked that testing it in critically ill patients was considered unethical.” Demasi continued, “Now, over 20 years after Tamiflu entered routine practice, researchers have finally done the randomized trial that should have preceded its use in critically ill influenza patients. And not only did they find no benefit—more patients died with Tamiflu than without it.”¹⁴

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