The combination of antidepressants and tamoxifen is not associated with an increased risk of breast cancer recurrence, according to a new study recently published in J Natl Cancer Inst by Haque and colleagues at the Kaiser Permanente Institute. The Lancet Oncology published a review article on Dec. 10 analyzing the risk of recurrence in breast cancer patients treated with tamoxifen who were also taking antidepressants. Reina Haque and colleagues evaluated the health records of 16,887 patients diagnosed with early-stage breast cancer between 1996 and 2007 who were treated with tamoxifen and antidepressants. The researchers observed the patients for breast cancer recurrence and followed them through Dec. 31, 2009. The researchers analyzed the proportion of time tamoxifen and antidepressants were present in the patients’ bodies at the same time, as well as the risk of secondary cancer. Of the 16,887 patients who received antidepressants in 8,099 (48%), 2,946 (36%) had secondary breast cancer (secondary breast cancer was defined as recurrent cancer in the ipsilateral breast, metastasis, or cancer found in the contralateral breast ≥6 months after the initial surgery). The investigators did not observe an increased risk of cancer recurrence with increasing rates of concurrent paroxetine and tamoxifen use during the first year of tamoxifen treatment (25% overlap between the two drugs: HR=1.06, 95% CI, 0.98-1.14, P=0.09; 50% overlap: HR=1.13, 95% CI, 0.98-1.30 , P=0.09; overlap ratio of 75%: HR=1.20, 95% CI, 0.97-1.49, P=0.09); in the first five years, the investigators also did not observe a significant difference in the risk of relapse. Similarly, among other antidepressants, the investigators did not find a correlation. The recommended duration of treatment for tamoxifen is five years, but significant adverse effects, including depression, can occur while taking the drug,” Haque told the Lancet Oncology journal. Since hormone replacement therapy is not recommended to alleviate these adverse symptoms in breast cancer survivors, prescriptions for antidepressants are gradually increasing in order to relieve symptoms.” She continued, “Considering that thousands of breast cancer survivors suffer from depression and other tamoxifen-induced adverse effects, our study helps allay the concerns of physicians who want to prescribe antidepressants in order to improve their patients’ quality of life while at the same time being concerned about it.” Stacie Dusetzina of the University of North Carolina commented, “Only a small percentage of women take a single antidepressant (3 percent took only paroxetine, while 23 percent took multiple types of antidepressants). Previous studies have shown that many women switch from taking antidepressants with stronger inhibitors (for CYP2D6 enzyme inhibitors, which metabolize tamoxifen to its active form) to antidepressants with weaker inhibitors, which could theoretically reduce the risk of relapse in these women.” Dusetzina concluded, “It would be more prudent to avoid stronger inhibitor antidepressants when choosing a new treatment for women who are taking tamoxifen.” In addition, Clin Pharmacokinet’s 2015, which has impact factor 5, has reported that fluoxetine and paroxetine conversion escitalopram treatment can increase tamoxifen active metabolite exposure as shown in the table below. And in 2015 Breast Cancer reported the results of a review study of pharmacotherapy and hormone therapy for the treatment of hot flashes symptoms in breast cancer patients showed that the combination of escitalopram, venlafaxine antidepressants and tamoxifen was not affected to improve the quality of life in breast cancer patients. This is because both SSRIs and SNRIs are CYP2D6 inhibitors, the same enzyme that metabolizes tamoxifen to endoxifen. Fluoxetine and paroxetine reduce the concentration of Endoxifen (the active metabolite of tamoxifen) due to their ability to reduce the concentration of Endoxifen. Therefore, fluoxetine should not be combined with tamoxifen. Citalopram and venlafaxine have weak 2D6 inhibition, so they can be combined.