In a new study, researchers did not find an increased risk of suicide among adolescent patients taking the drug oseltamivir (Tamiflu), the only commercially available medication approved by the U.S. Food and Drug Administration (FDA) to treat the flu.
After the drug’s approval in 1999, case reports began to emerge of abnormal behavior in adolescents who had taken the drug. This led the FDA to require that the medication come with a warning label of potential neuropsychiatric side effects, such as hallucinations, delirium, self-harm, and suicide.
So far, clinical studies examining a link between Tamiflu and neuropsychiatric side effects in children, including suicide, have been inconclusive, however. They have also been limited by methodology and potential confounding factors, according to researchers.
In an effort to fill this gap, researchers from the University of Illinois at Chicago (UIC) College of Pharmacy retrospectively studied the association between the use of Tamiflu and the most consequential of those reported side effects: suicide.
“I think physicians will welcome a large, rigorous study on this topic and factor this information into their decision-making process,” said corresponding author Dr. James Antoon, assistant professor of clinical pediatrics in the UIC College of Medicine.
“While this study addresses suicide, there are still many other questions about other possible neuropsychiatric side effects of the drug, which we plan to study in the future. There are also other reasons to use caution when prescribing the drug, including resistance and efficacy in children.”
First, the researchers identified 21,047 children and teens between the ages of one and 18 who attempted suicide during five recent flu seasons (2009-2013) from a national administrative claims database. Of these, 251 had been exposed to Tamiflu, which was determined based on outpatient pharmacy dispensing data.
The mean age of this group was 15 years, 61 percent were female, and 65 percent had an underlying mental health diagnosis.
“For each of the 251 patients, we assigned the 10-day period immediately before the suicide attempt as the case period and we identified up to four earlier control periods of the same length, in the same flu season,” Antoon said. “This helped us to account for within-person confounders, like depression, mental health, trauma and abuse, and other factors, like race or ethnicity.”
The research team repeated the analysis with flu diagnosis alone (without the use of Tamiflu) to determine whether the infection itself could have been a confounding factor associated with suicide risk.
“The potential link between a drug and suicide is a particularly difficult topic to study,” Antoon said. “Many events, which can happen simultaneously or over time, can influence a person to attempt suicide, as can an illness itself, so it can be difficult to study scientifically.
“That’s why we used a novel method called a case-crossover design,” Antoon said. “This analysis is different because it allowed us to use each individual subject as his or her own comparison — we retrospectively studied how patients behaved when on Tamiflu and compared it to their behavior when they were not taking the drug.”
“We did not find any association between exposure to Tamiflu and suicide in pediatric patients,” Antoon said.
While Antoon believes the study may alleviate some fears health care providers have about prescribing the medication in healthy children, he says doctors will likely continue to prescribe Tamiflu with caution.
The findings are published in the Annals of Family Medicine.