Antidepressant use tied to lower mortality in patients with hepatocellular carcinoma: JAMA

The population-based cohort study of 308,938 participants with hepatocellular carcinoma showed that antidepressant use after HCC diagnosis was associated with lower cancer-specific and overall mortality. The association was consistent across subgroups with different antidepressant classes and comorbidities.

Liver cancer is the sixth most commonly diagnosed cancer and is the third leading cause of cancer-related death worldwide, and among the different primary liver cancer forms, hepatocellular carcinoma is the most common, contributing to 75% to 90% of cases. Some previous studies have proposed that antidepressants may have apoptotic effects on cancer, but no study has investigated the association between antidepressant use and HCC prognosis.

Therefore, Kuan-Lun Huang, Ministry of Health and Welfare, Nantou, Taiwan, and colleagues conducted a national cohort study to investigate the association between antidepressants and HCC prognosis. They investigated overall and cancer-specific mortality as HCC prognosis indices. They distinguished between antidepressant use before and after HCC diagnosis to examine whether the timing of antidepressant use impacted the association with HCC prognosis.

For this purpose, the researchers analyzed Taiwan’s National Health Insurance Research Database, which covers 99% of Taiwan’s population and includes comprehensive medical information. They identified patients with a new diagnosis of hepatocellular carcinoma between 1999 and 2017.

All patients with hepatocellular carcinoma were followed up until 2018 to measure cancer-specific and overall mortality. Cox proportional hazards regression was performed to estimate hazard ratios (HRs) for the association between antidepressant use and overall mortality and cancer-specific mortality.

The study cohort comprised 308,938 participants, primarily consisting of older individuals (42.7% were aged ≥65 years) with a higher proportion of male individuals (65.6%).

The authors reported the following findings:

• Antidepressant use before the diagnosis of HCC was not associated with lower risks of overall mortality (adjusted HR, 1.10) and cancer-specific mortality (adjusted HR, 1.06).
• Antidepressant use after a diagnosis of HCC was associated with a lower risk of overall mortality (adjusted HR, 0.69) and cancer-specific mortality (adjusted HR, 0.63).
• 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.

"Our study provides promising empirical results indicating that antidepressants may be utilized as anticancer therapeutics in HCC patients," the researchers wrote.

They, however, caution that the findings should be interpreted cautiously because the associations found in the observational study may not suggest causality and may be affected by residual confounding or biases. They concluded that "definitive evidence would require evaluation in randomized clinical trials."

Reference:

Huang K, Chen Y, Stewart R, Chen VC. Antidepressant Use and Mortality Among Patients With Hepatocellular Carcinoma. JAMA Netw Open. 2023;6(9):e2332579. doi:10.1001/jamanetworkopen.2023.32579