Associations of oseltamivir with neuropsychiatric and behavioral adverse events: A systematic review and meta-analysis.

Background: Influenza causes approximately 3-5 million severe cases and 290,000-650,000 deaths annually, and oseltamivir is considered the first-line pharmacotherapy. Recent reports on neuropsychiatric events (NPEs) associated with the use of oseltamivir necessitated a systematic safety profile review.

Objective: To systematically review and meta-synthesize the evidence on the associations of oseltamivir with adverse NPEs and behavioral events.

Methods: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed/Medline, Embase, and Cochrane Library databases from inception through October 31, 2024. Studies comparing oseltamivir with other control groups for NPEs were analyzed. Outcomes were categorized into (1) affective disorders, (2) neuropsychiatric symptoms, (3) anxiety disorders, (4) schizophrenic/psychotic disorders, and (5) suicide-related behaviors.

Results: 9 studies with 1,139-3,352,015 patients were identified. Oseltamivir significantly associated with a lower overall NPE incidence (risk ratio [RR] = 0.83; 95% CI = 0.72-0.97), except in patients younger than 20 years. Subgroup analyses showed significant association with a lower incidence risk in suicide attempts across all ages (RR = 0.60; 95% CI = 0.46-0.77) and in schizophrenia/psychotic disorders for patients younger than 20 years (RR = 0.75; 95% CI = 0.61-0.93).

Conclusions: This is the first comprehensive meta-analysis examining the associations of oseltamivir with various NPEs and behavioral adverse events, and we found no evidence supporting increased risks of these adverse events with oseltamivir use.