Use of antidepressants and risk of colorectal cancer: a nested case-control study.

Background: Animal studies suggest that selective serotonin reuptake inhibitors (SSRI) retard the growth of colorectal tumours, whereas tricyclic antidepressants increase the risk of colorectal cancer. We aimed to assess whether SSRI use was associated with a decreased risk of colorectal cancer, and tricyclic-antidepressant use with an increased risk of colorectal cancer.

Methods: We did a population-based nested case-control study from Jan 1, 1981, to Dec 31, 2000, of people aged 5-85 years who were registered with Saskatchewan Health and eligible for prescription-drug benefit. Between Jan 1, 1981, and Dec 31, 2000, 6544 cases with colorectal cancer were identified from the Saskatchewan Cancer Agency registry and analysed for use of tricyclic antidepressants; between Jan 1, 1991, and Dec 31, 2000, 3367 cases with colorectal cancer were identified from the Saskatchewan Cancer Agency registry and analysed for SSRI use. For every case, four eligible controls matched for age, sex, and calendar time (ie, free of any cancer in calendar month of case diagnosis) were selected randomly by a statistician who used incidence density sampling. By use of conditional logistic regression, we assessed incidence-rate ratios of having colorectal cancer in association with use of antidepressants, analysing dose and time of use.

Findings: A decreased risk of colorectal cancer was associated with high (ie, >6.0x10(-6) mol per day) daily SSRI dose during 0-5 years before diagnosis (incidence-rate ratio 0.70 [95% CI 0.50-0.96], p for trend=0.0172), adjusted for age, sex, use of non-steroidal anti-inflammatory drugs in the same period, and SSRI use during 6-10 years before index date (ie, date of diagnosis for a case and the same date for matched controls). No consistent relation was recorded for risk of colorectal cancer and use of tricyclic antidepressants.

Interpretation: SSRI use might inhibit the growth of colorectal tumours through an antipromoter effect or direct cytotoxic effect. Further investigation is needed, with more complete assessment of confounders such as lifestyle factors (eg, diet), use of drugs, and comorbidity (eg, diabetes or inflammatory bowel disease) that might affect the occurrence of colorectal cancer.