Antidepressants and Risk of Liver Cancer: A Systematic Review and Meta-Analysis

Background: Previous results regarding the association between the antidepressants use and risk of liver cancer are controversial. Objective: This study aimed to assess whether antidepressants use increases liver cancer risk. Methods: We systematically searched several English and Chinese databases, including the Cochrane Library, MEDLINE, Embase, PsycINFO, Web of Science, CNKI, CQVIP database, Wanfang database, and SinoMed, and 3 clinical trial registration platforms through May 2022. Observational studies evaluating liver cancer risk in patients on antidepressants use were included, and the quality of studies was assessed using the Newcastle-Ottawa scale. A random-effects model was used to calculate the pooled effect estimates and 95% confidence intervals (CIs). Results: We included 11 studies with a total of 132 396 liver cancer cases. The meta-relative risk (RR) for liver cancer associated with antidepressants use was 0.72 (95% CI 0.59-0.86). In subgroup analyses, only selective serotonin reuptake inhibitors were negatively correlated with risk of liver cancer (RR 0.64, 95% CI 0.51-0.79); both dose subgroups <= 365cDDD (RR 0.77, 95% CI 0.69-0.85) and >365cDDD (RR 0.57, 95% CI 0.40-0.81) were associated with lower liver cancer risk; only in patients with chronic viral hepatitis, the use of antidepressants reduced liver cancer risk (RR 0.70, 95% CI 0.54-0.90). Conclusions and Relevance: The result of the current meta-analysis shows antidepressants use is not associated with increased risk of liver cancer and appears to be correlated with decreased risk. However, the observed association needs to be verified by more powerful evidence from prospective, methodologically rigorous studies.