A real-world pharmacovigilance study of adverse events associated with esketamine: disproportionality analysis and detection of potential drug-drug interaction signals.

PURPOSE: We conducted a comprehensive analysis of esketamine-related adverse events (AE) on the FDA Adverse Event Reporting System (FAERS) database, taking into account for the first time drug-drug interaction signals.

METHODS

We conducted a retrospective case/non-case study of esketamine-related AEs reported in the FAERS database up to the last quarter (Q4) of 2024. Potential signals were detected using the reporting odds ratio (ROR) and confidence intervals (CI), while drug-drug interactions were studied using different metrics such as lift, conviction and the combination risk ratio detection algorithm. An analysis of sex differences was also performed using the relative ROR and CI.

RESULTS

The analysis of 7,790 reports in which esketamine was a primary or secondary suspect identified potential safety signals for 173 AEs. Novel signals include homicidal ideation (ROR = 5.30, 95% CI: 2.38-11.82) and substance use disorder (ROR = 6.12, 95% CI: 2.54-14.73). Women showed a longer time to onset than men (p = 0.003). In addition, we detected sex differences in 23 AEs, seven of which were more likely to be reported in women, while 16 in men. Among these, four were significant exclusively in women (oxygen saturation decreased, abnormal behaviour, unresponsive to stimuli and aggression) and two in men (vision blurred and bradycardia). Potential signals of additive and multiplicative drug-drug interactions were detected for antidepressants (venlafaxine for"dizziness" and bupropion for "agitation") and antipsychotics (risperidone for "vertigo").

CONCLUSIONS

Our results increase knowledge on potential risks related to esketamine AEs and potential drug-drug interaction signals in a real-world setting.