Discussion
comorbidity, death, HBV infection, cancer, noncancer, unintentional injury, HCV infection, HCC, depression
DISORDER, CANCER, LIVER CIRRHOSIS
This is the first national cohort study on the association between antidepressant use and mortality risk in patients with HCC. Our results demonstrate that the use of antidepressants after HCC diagnosis, including SSRI, SNRI, and TCA, was associated with decreased both overall and cancer-specific mortality in a large, representative cohort. Notably, we observed a consistent inverse association between postdiagnosis antidepressant use and mortality risk across various comorbidity subgroups, encompassing HBV infection, HCV infection, liver cirrhosis, and alcohol use disorder. In contrast, no association was observed between the use of antidepressants before HCC diagnosis and reduced cancer-specific mortality or all-cause mortality.Our study conducted 2 comparisons; examining the associations of antidepressant use before and after HCC diagnosis with mortality. The results showed inconsistent findings. Antidepressant use before HCC diagnosis was not associated with lower mortality risk, indicating that the antidepressant use prior to HCC diagnosis may not have an association with the severity of HCC and its subsequent prognosis. However, the use of antidepressants after HCC diagnosis was inversely associated with both overall and cancer-specific mortality. This suggests that antidepressant use might be involved in the prognosis of cancer, not before its induction. A similar finding was also observed that statin use after HCC diagnosis associated with lower HCC mortality but not in statin use before HCC diagnosis.Considering the inverse association between overall mortality and antidepressant use after HCC diagnosis, several noncancer causes of death, such as unintentional injury, self-inflicted injury, and suicide, have been reported in patients with cancer, which may be reduced by antidepressant use. For example, risks of motor vehicle crashesIn addition to observing lower risk of overall mortality, we observed that antidepressant use after HCC diagnosis was inversely associated with cancer-specific mortality. This association remained consistent when specifically analyzing different antidepressants including SSRIs, SNRIs, and TCAs. This might be explained by previously reported apoptotic effects of serotonergic antidepressants on cancer through the regulation of growth stimulatory 5-HT activity connected to biochemical pathways involving mitogen-activated protein kinase, mitochondrial membrane potential, extracellular signal-regulated kinases, protein kinase B, and nuclear transcription factor-κB.Despite biological plausibility, studies have presented mixed results for associations of antidepressants with mortality in patients with cancer. Some studies have reported that antidepressant use in patients with depression and cancer has a beneficial effect on premature mortality,