The antiviral medication oseltamivir does not increase the risk for suicide in children being treated for influenza, a new study suggests.
The findings, reported by Rachel Harrington and colleagues in an article published online March 12 in the Annals of Family Medicine, should greatly reassure physicians who prescribe the drug to children, according to a pediatric infectious disease expert.
Previous case reports and small epidemiologic studies have linked oseltamivir with various neuropsychiatric effects, including abnormal behavior, psychosis, and suicide, but the findings have been inconsistent and limited by study size and design, write Harrington, from the University of Illinois at Chicago College of Pharmacy, and colleagues. Further, prior observational studies looking specifically at the potential association with suicide relied on older data or a single influenza season and included suicide only as a secondary outcome, they note.
In contrast, the current investigation examined the oseltamivir–suicide association using recent administrative claims data covering five influenza seasons. To minimize potential confounding, the researchers used a case-crossover design, whereby the 10-day period before a suicide attempt was considered the case period and up to four earlier periods of the same length from the same influenza season were considered control periods. Exposure to oseltamivir was assessed for case and control periods.
For the influenza seasons from 2009 to 2013 (October 1 through April 30), an analysis of an administrative claims database consisting of 50 million beneficiaries across all 50 states identified 21,047 individuals aged 18 years or younger with an inpatient or outpatient claim associated with attempted suicide. Of those, 251 children (mean age, 15 years) had been exposed to oseltamivir at the time of their suicide attempt.
In the primary analysis looking at the association between oseltamivir exposure and suicidality, the odds ratio (OR) of oseltamivir exposure during the case period compared with control periods was 0.64 (95% confidence interval [CI], 0.39 – 1.00).
In a secondary analysis looking specifically at 162 individuals exposed only to influenza, the OR for suicide attempt was similar (OR, 0.63; 95% CI, 0.34 – 1.08), “suggesting no confounding by indication of underlying influenza,” they state.
The magnitude and direction of the findings remained consistent in sensitivity analyses looking at alternative case and control periods, the authors note.
Although two findings were statistically significant: a 15-day window analysis of oseltamivir exposure (OR, 0.57; 95% CI, 0.36 – 0.86; P = .007) and a 5-day window analysis of influenza-only exposure (OR, 0.48; 95% CI, 0.22 – 0.95; P = .03), these associations should be interpreted with caution, the authors state. “For instance, the 15-day window analysis of oseltamivir, although biologically plausible, extends the drug’s effect duration to its extreme. This extension may lead to an exaggeration of the effect due to misclassification of the case period as ‘exposed.’ “
Although the findings may be limited by possible underidentification of suicide attempts and the artificial definition of the influenza season by the same dates each year, which doesn’t reflect actual season variability, “our results suggest that oseltamivir does not increase the risk of suicide in the pediatric population,” the authors write. The case-crossover design addresses the possibility that the findings would be limited by such confounders as trauma, abuse, mental health status, or race, as has been the case in prior studies, they note.
The findings should reassure prescribing physicians that the benefits of oseltamivir outweigh the risks in treating pediatric influenza, according to Susan E. Coffin, MD, professor of pediatrics at the University of Pennsylvania School of Medicine and associate chief of the Division of Infectious Diseases at Children’s Hospital of Philadelphia. “The risk of a bad outcome associated with influenza is well documented and much greater than the poorly supported association between antiviral medications and psychiatric events.”
Regarding previously described adverse events associated with the medication, “data from well done studies have not been convincing, especially in US populations,” she said.
The study authors and Coffin have disclosed no relevant financial relationships.
Ann Fam Med. 2018;16:145-148.
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