Meta-Analysis Shows Certain Antidepressants May Increase Lung Cancer Risk

Antidepressants—serotonin and norepinephrine reuptake inhibitors (SNRIs) specifically—may increase the risk of lung cancer, according to a new meta-analysis.

The findings add complexity to previous research that suggests antidepressants may have anticarcinogenic or tumor-suppressive effects on certain types of cancer. The analysis was published in Cancer Research Communications.

Lung cancer remains the leading cause of cancer-related deaths worldwide, noted the study authors. One reason the cancer type is so deadly is that it can be difficult to detect cases early enough for curative treatment, they added. Given this context, they emphasized it is important to better understand the factors that can affect an individual’s level of lung cancer risk.

Recently, in vitro and preclinical studies have suggested that certain antidepressant drugs, including tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), may have anticancer effects in several types of cancer, including cervical cancer, gastric cancer, and hepatocellular carcinoma, the authors said. However, other studies have suggested antidepressants can also promote cancer growth in certain situations, including in fibrosarcoma and melanoma. In lung cancer specifically, the effect of antidepressant use remains unclear. The investigators noted that overall use of antidepressants is increasing, including among people trying to quit smoking and people with depression. Both a history of smoking and depression are common in patients with lung cancer.

To find out how—if at all—antidepressants affect lung cancer risk, the authors searched several scientific databases to find studies related to antidepressants, lung cancer incidence, and lung cancer survival. They found 11 studies, covering more than 1.2 million participants, that met their inclusion criteria.

Their data suggest that antidepressants use was associated with an 11% higher risk oflung cancer. Specifically, the authors found patients who used antidepressants had a 1.11 pooled risk ratio (RR; 95% CI, 1.02-1.20) for lung cancer. However, there was not a statistically significant difference in survival outcomes between those with lung cancer who had been treated with antidepressants and those who had not.

The authors noted that the finding that antidepressants increased the risk of lung cancer contrasts with some previous meta-analyses.

“The discrepancy in the results may be due to the differences in the types of ADs [antidepressants], cancer type, study design, and the number of studies included in the meta-analysis,” they wrote.

Indeed, they found that SNRIs were most closely associated with an elevated risk of lung cancer (RR 1.38; 95% CI, 1.07-1.78). Other research has suggested that SNRIs can lead to DNA damage, which the investigators said may be the avenue by which the drugs affect lung cancer risk. However, they said additional research would be needed to confirm their findings.

The authors noted several strengths and limitations to their study. They said theirs is the first meta-analysis to look specifically at observational studies assessing lung cancer risk and survival with AD use, but they also noted that the meta-analysis was based on a small number of studies due to the lack of available research.

Still, they said their findings suggest the question of antidepressants and lung cancer risk warrants more investigation.

“To increase the evidence, well-designed prospective cohort studies are needed, where commonly used ADs (SSRIs, SNRIs, and TCAs) are evaluated on cancer outcomes in individuals with lung cancer and with or without a diagnosis of depression,” they concluded.

Reference

Lee E, Park Y, Li D, Rodriguez-Fuguet A, Wang X, Zhang WC. Antidepressant use and lung cancer risk and survival: a meta-analysis of observational studies. Cancer Res Commun. 2023;3(6):1013-1025. doi:10.1158/2767-9764.CRC-23-0003