Dextromethorphan-bupropion-associated pharmacovigilance signals based on the FAERS database: An observational study.

An analysis of the FDA adverse event reporting system from late 2022 through 2024 identified 3,580 adverse events linked to dextromethorphan-bupropion, a drug for major depressive disorder approved in August 2022. The most common adverse events were psychiatric disorders (21.17%), nervous system disorders (20.92%), and general disorders or administration site conditions (19.75%). Obsessive rumination, though rare, showed the strongest statistical signal. Notably, 65.3% of the reported adverse event signals were not listed in the drug's official prescribing instructions, suggesting previously unrecognized risks. Clinicians should monitor for these events, especially those not mentioned in the label.

Study at a glance

Abstract

Dextromethorphan-bupropion, a novel oral N-methyl-D-aspartate receptor antagonist approved by the Food and Drug Administration in August 2022, launched in the United States in October 2022 for major depressive disorder. We aimed to detect and characterize the adverse events (AEs) of dextromethorphan-bupropion using the FDA adverse event reporting system from the 4th quarter of 2022 to the 4th quarter of 2024. For signal quantification of dextromethorphan-bupropion-related AEs, we used disproportionality methods including the reporting odds ratio, proportional reporting ratio, and multi-item gamma Poisson shrinker algorithms. Our study analyzed 4,804,129 AEs, while 3580 AEs were associated with dextromethorphan-bupropion, which included 266 preferred term signals and 21 system organ classes. These AEs mainly occurred as psychiatric disorders (21.17%), nervous system disorders (20.92%), general disorders, administration site conditions (19.75%), and others. Notably, obsessive rumination (n = 3, reporting odds ratio = 366.02, proportional reporting ratio = 365.71, empirical Bayes geometric mean = 287.56) exhibited the lowest morbidity, whereas the highest signal intensity. Specifically, 65.3% of preferred terms were not explicitly mentioned in the instructions, which suggested the previously unlabeled signals. Dextromethorphan-bupropion poses potential reporting signals of various AEs, though providing therapeutic effects. In clinical applications, practitioners should closely monitor occurrences of psychiatric disorders, nervous system disorders, general disorders, administration site conditions, and other events. Meanwhile, professional clinicians should be alerted to the AEs signals not mentioned in the label to secure clinical use.