Antidepressant Use Lowers Mortality Risk in HCC


Recent findings identified that overall and cancer-specific mortality risks were lowered in patients who used antidepressants following a diagnosis with hepatocellular carcinoma compared with patients that did not.

3d illustration of human body liver: © PIC4U -

3d illustration of human body liver: © PIC4U -

The use of antidepressants after a diagnosis with hepatocellular carcinoma (HCC) was associated with lower cancer-specific and overall mortality, even across different types of antidepressants and patient comorbidities, according to a study published in the Journal of the American Medical Association.1

Investigators found that antidepressant use after an HCC diagnosis demonstrated reduced risks of overall mortality (HR, 0.69; 95% CI, 0.68-0.70) and cancer-specific mortality (HR, 0.63; 95% CI, 0.59-0.68). However, antidepressant use before HCC diagnosis was not related to lowered overall mortality risk (HR, 1.10; 95% CI, 1.08-1.12) or cancer-specific mortality (HR, 1.06; 95% CI, 0.96-1.17).

“Adherence to antidepressant treatment has been shown to have a positive impact on mortality in patients with depression and cancer. It is possible that the prescription of antidepressants may act as a mediator, indirectly influencing the overall mortality risk in patients with HCC by mitigating the negative health effects of depression,” study authors wrote.

In patients who used antidepressants after HCC diagnosis, the crude overall mortality rate was 10.03 per 100 person-years compared with 15.45 per 100 person-years in the nonuser group. The use of any antidepressant was linked with a lower mortality risk (HR, 0.69; 95% CI, 0.86-0.70); however, the lowest mortality risks were associated with selective serotonin reuptake inhibitors (SSRIs; HR, 0.62; 95% CI, 0.61-0.64), selective norepinephrine reuptake inhibitors (SNRIs; HR, 0.60; 95% CI, 0.57-0.62), and tricyclic antidepressants (TCAs; HR, 0.60; 95% CI, 0.59-0.60).

For cancer-specific mortality, the rate was 0.32 per 100 person-years in the combined antidepressant group, 0.12-0.15 per 100 person-years in the different antidepressant subgroups, and 0.54 per 100 person-years in the nonuser group. Again, SSRIs (HR, 0.53; 95% CI, 0.47-0.61), SNRIs (HR, 0.54; 95% CI, 0.42-0.68), and TCAs (HR, 0.54; 95% CI, 0.49-0.59) were associated with the lowest cancer-specific mortality.

Short-term (less than 90 days) vs long-term (more than 90 days) antidepressant use did not appear to affect overall or cancer-specific mortality rates.

Investigators identified 308,938 patients with HCC between the years of 1999 and 2017. A total of 21,202 patients who had used antidepressants within 1 year of HCC diagnosis were identified, leaving a pre-HCC diagnosis nonuser group of 287,736 patients. Regarding antidepressant usage after HCC diagnosis, 66,211 patients were identified that had used antidepressants.

SSRIs, SNRIs, and TCAs were evaluated as groups with no distinction for specific drug within each group, and the atypical antidepressants bupropion (Wellbutrin), mirtazapine (Remeron), and trazodone (Desyrel) were categorized individually.

“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 crashesand suicide attempts have been reported to decrease following the initiation of antidepressant treatment,” study authors wrote.

As depression is a comorbidity than can occur after up to approximately 25% of patients with cancer,2 and a 2023 study found that the risk of suicide was 26% higher in patients with cancer compared with the general population.3 These findings signal the importance of psychological interventions and symptom management in the oncology treatment landscape.

1. 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
2. Depression (PDQ)—health professional version. National Cancer Institute. Updated September 1, 2023. Accessed November 30, 2023.
3. Hu X, Ma J, Jemal A, et al. Suicide risk among individuals diagnosed with cancer in the US, 2000-2016. JAMA Netw Open. 2023;6(1):e2251863. doi:10.1001/jamanetworkopen.2022.51863
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