Comparing the adverse effects of ketamine and esketamine between genders using FAERS data.

Background: Ketamine was developed as an anesthetic. Esketamine is the isolated S-enantiomer of racemic ketamine. They provide new avenues for the treatment of depression, especially treatment-resistant depression. Considering differences in the pharmacokinetics and hormonal status of ketamine in patients of different genders, sex-based differences in esketamine adverse drug events (ADE) may also be observed. This study presents data mining and safety analysis of adverse events of ketamine and esketamine between genders, promoting the individualization of clinical practice. Methods: Adverse drug reactions to ketamine and esketamine reported between the first quarter of 2004 and the second quarter of 2023 in the U.S. Food and Drug Administration on Adverse Event Reporting System (FAERS) were extracted. Thereafter, the reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated. Results: A total of 2907 female reports and 1634 male reports on esketamine were included in the analysis. ROR mining showed that completed suicide, decreased therapeutic product effects, urinary retention, and hypertension were common in men. Additionally, 552 female and 653 male ketamine reports were recorded. ROR mining revealed that toxicity to various agents, bradycardia, cystitis and agitation, were more likely to occur in men, whereas women were more likely to develop suicidal ideation, increased transaminase levels, sclerosing cholangitis, and sterile pyuria. Conclusion: The adverse events of esketamine and ketamine differ across genders, which should be considered in clinical practice to provide individualized treatment.