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Background: Many of the newer antidepressants used to treat hot flushes and depression inhibit the CYP2D6 enzyme, which is important for tamoxifen activation in breast cancer patients.Concomitant CYP2D6 inhibitor use in tamoxifen treated patients, as well as non-functional CYP2D6 alleles, have been associated with worse clinical outcome.We aimed to examine the frequency of antidepressant use and the use of drugs not recommended concomitantly with tamoxifen due to drug interactions among breast cancer patients.Methods: Pre-operative questionnaires containing questions about lifestyle and concomitant medication use during the past week were completed by 425 primary breast cancer patients.Follow-up questionnaires were completed three to six months, one year, two years and three years post-operatively.Clinical information on breast cancer was obtained from clinical records and tumor characteristics from pathology reports.Results: Pre-operatively, 10.4% of patients used antidepressants, three times the frequency in the general population of middle-aged women from the same area.Antidepressant use remained constant during the three-year follow-up.Few women reported starting antidepressants post-operatively.Antidepressant use was similar in patients with and without tamoxifen.Antidepressant use was significantly associated with the use of anxiolytics, sleeping pills and being a teetotaler.Median follow-up time was one year.Among tamoxifen treated women, antidepressant use increased the risk of early breast cancer events HR1.9 (95% CI 0.52-7.1).Conclusion: Between 2.2% and 5.3% oftamoxifen treated patients used either potent or moderate CYP2D6 inhibitors during the first three-years postoperatively.Potential drug-interactions with tarnoxifen may be of clinical significance.