Despite this evidence, other studies have not found an association between tamoxifen and depressed mood in patients with breast cancer. One group of researchers who assessed various symptoms self-reported by postmenopausal women who were breast cancer survivors found that the depression scores were not significant.14 A retrospective cohort study assessed the onset of depression in patients with breast cancer with positive hormone receptor status (who received tamoxifen) vs negative hormone receptor status (who did not receive tamoxifen). These researchers did not find a statistically significant hazard ratio for “new-onset depression.”15 Unfortunately, the criteria for “new-onset depression” used in this study was the diagnosis of depression or use of an antidepressant given or ordered by a clinician, which is not a sensitive assessment of depressed mood.15
A multicenter randomized, placebo-controlled trial (the National Surgical Adjuvant Breast and Bowel Project) assessed the incidence of negative health outcomes, including depression, in a secondary outcome analysis.16 These researchers did not find a statistically significantassociation between tamoxifen and depression. However, in this study, assessment of depression was based on self-report using the Center of Epidemiologic Studies Depression (CES-D) scale, which does not clinically categorize depression. Furthermore, these researchers strongly recommended screening for mood disorders in routine clinical practice. In this study, 3 women completed suicide, 2 of whom were in the tamoxifen arm.16
The authors’ observations
Tamoxifen is a prodrug that converts to the active metabolite, endoxifen, via cytochrome P450 2D6 (CYP2D6) activity. Antidepressants with strong 2D6-inhibiting properties, such as fluoxetine, duloxetine, bupropion, and paroxetine, should be avoided in patients receiving tamoxifen because they interfere with the formation of the active metabolite and could reduce the effectiveness of tamoxifen and its ability to reduce the risk of cancer recurrence.17 Antidepressants can help treat psychological distress, especially depression, which is common in patients with cancer, and vasomotor symptoms, which may impair quality of life and adherence to long-term endocrine therapy. Because tamoxifen can decrease cancer recurrence and associated mortality,18 adherence with treatment is crucial.
TREATMENT Starting an antidepressant
The psychiatry team initiates venlafaxine, 37.5 mg/d, to treat Mrs. L’s anxiety and help prevent the recurrence of severe depression. They prescribe venlafaxine because they anticipate that, based on Mrs. L’s age, the oncology team might reconsider treatment with tamoxifen. Venlafaxine is preferred because it has a favorable pharmacodynamic profile and does not interfere with the metabolism of tamoxifen, as is the case with many selective serotonin reuptake inhibitors.17
Although Mrs. L’s depression had abated once she stopped receiving tamoxifen, she continues to experience anxiety and tearfulness, primarily due to fear of adverse effects of hormone therapy, and due to family as well as work stressors. Therefore, venlafaxine is gradually titrated up to 150 mg/d.
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