Risk of stress cardiomyopathy associated with selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors: A real-world pharmacovigilance analysis

Abstract Objective Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are the two commonly prescribed antidepressants, but these drugs have been reported clinically to cause stress cardiomyopathy (SC). This study aimed to evaluate the possible association between SSRI or SNRI usage and the occurrence of cardiomyopathy by mining the publicly available U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods The disproportionate analysis and likelihood ratio test were employed to identify risk signals associated with the use of SSRIs or SNRIs and the incidence of stress cardiomyopathy. The raw data was sourced from the FAERS database from 2012 to 2022. Descriptive statistics were further applied to present the demographic characteristics, time to onset, concomitant medications and prognostic outcomes. Statistical analysis and data visualization were conducted using the R v4.0.2. Results In total, 132 individual case safety reports (ICSRs) of SC associated with SSRIs or SNRIs were identified. Venlafaxine and fluoxetine were identified as the most commonly suspected antidepressant medications, accounting for 48% and 27% of the ICSRs, respectively. Approximately 80% of SC cases were reported in females, with individuals aged 45–65 identified as a high-risk population. The reporting regions were mainly in Europe and North America, with differences in antidepressant utilization preferences between geographic regions. Both venlafaxine (RSIC 2.54, 95%CI 2.06 to 3.04) and fluoxetine (RSIC 3.20, 95%CI 2.31 to 4.47) exhibited a significant disproportionality of SC, with likelihood ratio estimates of 3.55 (p = 0.02) for venlafaxine and 4.82 (p = 0.008) for fluoxetine. Propofol, lidocaine, oxycodone, gabapentin and zonisamide were the frequently co-administered with SSRIs or SNRIs. The median time to cardiomyopathy onset was 20 days. The most frequently reported outcomes were hospitalization or prolonged hospitalization in 48.33% of patients, and other serious events occurred in 12% of patients. Conclusion This analysis based on the FAERS database provided new insight into the main characteristics of adverse cardiomyopathic events associated with SSRIs and SNRIs in real-world. The risk of cardiomyopathy varied between SSRIs and SNRIs, and there was a significant disproportionate risk signal associated with stress cardiomyopathy, particularly in middle-aged women for venlafaxine and fluoxetine. Caution should be exercised when SSRIs or SNRIs are used with other serotonergic medications.