Tamoxifen and depression: More evidence from the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention (P-1) randomized study

Background: Concerns have been raised that tamoxifen may be associated with depression. To investigate this question, we examined the psychological effects of tamoxifen treatment for breast cancer prevention on women at different levels of risk for clinical depression who were enrolled in the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention (P-1) Study. Methods: A total of 11 064 women were randomly assigned to receive for 5 years daily doses of 20 mg of tamoxifen or placebo in the P-1 study, a multicenter, double-blind, placebo-controlled chemoprevention trial. Each woman was prospectively assessed for depression risk on the basis of medical history items collected at the baseline examination and placed in a high-, medium-, or low-risk group. Every 6 months, for a total of 36 months, the participants were assessed for depressive symptoms by completing the Center for Epidemiological Studies-Depression (CES-D) questionnaire. Scores of 16 or higher were indicative of an episode of affective distress. Differences between the risk groups and treatment arms were analyzed by logistic regression. All statistical tests were two-sided. Results: Women in the higher risk depression groups were more likely to score 16 or higher on the CES-D (percent follow-up examinations with a score of greater than or equal to 16: highrisk group = 35.7%, with 95% confidence interval [CI] = 32.5% to 38.9%; medium-risk group = 19.2%, with 95% CI = 18.1% to 20.3%; and low-risk group = 8.7%, with 95% CI = 8.3 to 9.1 %) and to have these scores more frequently and for longer periods than women in the lower risk groups. Within each depression risk group, there was no difference in the proportion of women scoring 16 or higher by treatment assignment (tamoxifen versus placebo) (odds ratio = 0.98; 95% CI = 0.93 to 1.02). A post-hoe analysis indicated that the lack of a tamoxifen effect was not a result of differential missing data. Conclusions: Physicians need not be overly concerned that treatment with tamoxifen will increase the risk for or exacerbate existing depression in women. Nevertheless, physicians should continue to screen for and treat or refer potential cases of depression encountered in routine clinical practice.