Importance: Liver cancer, primarily hepatocellular carcinoma (HCC), is the third leading cause of cancer deaths worldwide. Although some studies have proposed that antidepressants may have apoptotic effects on cancer, no study has examined the association between antidepressant use and HCC prognosis.
Objective: To investigate the association between antidepressant use and mortality risk in patients with HCC.
Design, setting, and participants: This population-based cohort study analyzed Taiwan's National Health Insurance Research Database, which covers 99% of Taiwan's population and includes comprehensive medical information. Patients with a new diagnosis of HCC between 1999 and 2017 were identified. Analysis took place in June 2023.
Main outcomes and measures: All patients with HCC were followed up until 2018 to measure overall and cancer-specific mortality. To examine whether the timing of antidepressant use influenced the association with mortality, antidepressant use was examined before and after HCC diagnosis. Cox proportional hazards regression was performed to estimate hazard ratios (HRs) and the 95% CIs for the association between antidepressant use and overall mortality and cancer-specific mortality.
Results: The study cohort comprised 308 938 participants, primarily consisting of older individuals (131 991 [42.7%] were aged ≥65 years) with a higher proportion of male individuals (202 589 [65.6%]). Antidepressant use before the diagnosis of HCC was not associated with lower risks of overall mortality (adjusted HR, 1.10; 95% CI, 1.08-1.12) and cancer-specific mortality (adjusted HR, 1.06; 95% CI, 0.96-1.17). However, antidepressant use after a diagnosis of HCC was associated with a lower risk of overall mortality (adjusted HR, 0.69; 95% CI, 0.68-0.70) and cancer-specific mortality (adjusted HR, 0.63; 95% CI, 0.59-0.68). The observed associations were consistent across subgroups with different antidepressant classes and comorbidities, including hepatitis B virus or hepatitis C virus infection, liver cirrhosis, and alcohol use disorders.
Conclusions and relevance: Based on this nationwide cohort study, postdiagnosis antidepressant use may be associated with lower mortality in patients with HCC. Further randomized clinical trial evaluation should be considered.