Colorectal cancer risk in relation to antidepressant medication use

Abstract

Laboratory studies suggest that antidepressants affect the risk of some cancers, including colorectal cancer. To investigate whether selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are associated with colorectal cancer risk, we conducted a case-control study among enrollees of an integrated healthcare delivery system in Washington State. Cases were first diagnosed with invasive colorectal cancer between 2000 and 2003; controls were randomly selected from Group Health enrollees and matched to cases on age, sex and length of enrollment before diagnosis/reference date. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for colorectal cancer in relation to use of any antidepressant, SSRIs only or TCAs only, among 649 cases and 656 controls. Use of any antidepressant was associated with a reduced risk of colorectal cancer (OR 5 0.7, 95% CI 5 0.5-0.9). Associations were similar for persons who used SSRIs exclusively (OR 5 0.7, 95% CI 5 0.4-1.1) and TCAs exclusively (OR 5 0.7, 95% CI 5 0.5-1.2); however, this reduction in risk appeared limited to persons without a prior cancer at another site. Our data support findings from previous epidemiologic and animal studies that suggest antidepressants may reduce the risk of colorectal cancer. Future studies with larger sample sizes should further examine individual drugs as well as dose, duration and recency of use.Antidepressant use is on the rise in the United States, 1 and it is important to determine what role, if any, these medications might play in altering the risk of diseases such as cancer. There have been several reports of null associations between use of antidepressants and the risk of breast 2,3 and ovarian 4-6 cancers. However, there is a lack of research on these relatively commonly used medications in relation to other major causes of cancer mortality, including colorectal cancer. A large epidemiologic study reported that serotonin reuptake inhibitors (SSRI) use reduced risk of colorectal cancer but observed no association with use of tricyclic antidepressants (TCA). 7 Another large study observed an increased risk of colon cancer with >4 years use of non-SSRI antidepressants. 8 A recent study noted a reduced risk of colorectal cancer associated with SSRI use and a nonsignificant reduction with TCA use. 9 Laboratory evidence suggests a decreased risk of colorectal cancer associated with SSRI use. In mice xenografted with human colorectal carcinomas, administration of antiserotoninergic agents, including the SSRIs fluoxetine and citalopram, 10 reduced colorectal tumor growth, as measured by tumor volume, compared with controls. [10][11][12] In rats, the mitotic rate of chemically induced colonic tumors was lower in those subsequently treated with antiserotoninergic agents compared with controls injected with saline. 10,13 These studies, along with in vitro studies of human colorectal cancer cell lines treated with SSRIs, 14,15 suggest that SSRIs may impede growth of colorectal tumors.Ev...

Antidepressant fluoxetine and its potential against colon tumors

“…We then reported that FLX could also reduce pre-existent colon preneoplastic lesions [64] . Our findings suggested that FLX takes the carcinogen-induced preneoplastic changes under control by reducing epithelial proliferation [38,56,60,61,64,65] . Besides the fact that FLX treatment reduced dysplasia and preneoplastic angiogenesis, decreasing the epithelial and subepithelial proliferation [64,65] , our unpublished dataset further suggests that by suppressing the NF-κB nuclear activity, through increased expression of cytoplasmic NF-κB-inhibitor IκB-α and IκB-β proteins, FLX reduced c-Myc expression and then stromal proliferation (Figures 2 and 3).…”

“…In patients, FLX treatment was reported to reduce the risk of colon cancer to almost 50% [60] . Chubak et al [61] also observed that FLX reduced the risk of colon cancer in humans, while one meta-analysis study suggested that FLX does not act on colon cancer [62] . Studies with animal models support the idea of FLX reducing colon cancer incidence in different animal models, such as carcinogen induced preneoplastic lesions and tumors in rats and mice, and xenograft tumors in immunosuppressed rats [38,[63][64][65] .…”

Antidepressant use and risk of central nervous system metastasis

“…Conflicting results of antidepressant use and de novo cancer risk have been reported [264][265][266][267][268][269][270]. A case-control study found no association between antidepressant use and breast cancer risk; a protective effect of paroxetine hydrochloride was observed in subjects who were not overweight [264].…”

“…A nested case-control study found a protective effect of SSRIs on the risk of lung cancer, but a non-significant elevated risk with tricyclic antidepressants; the authors attribute the potential effects to residual confounding [267]. A reduced risk of colorectal cancer was seen with antidepressant use [268,269]. The association between antidepressants and breast cancer and antidepressants and ovarian cancer are mixed in the preclinical and clinical data.…”

“…Studies exist determining if an association exists between antidepressant use and cancer risk [264][265][266][267][268][269][270]283] and antidepressant use and recurrence of cancer [258,272,277,278], but to our knowledge, no studies exist determining if antidepressant use is associated with an increase in brain metastasis in humans. Shapovalov et al found an association between pretreatment with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and an increase in brain metastasis from breast cancer in mice [14].…”