Breast Cancer Recurrence Risk Related to Concurrent Use of SSRI Antidepressants and Tamoxifen

Background:
Up to one-quarter of breast cancer patients suffer clinically significant depression in the year after diagnosis, which may respond to intervention. About half may be prescribed a psychotropic medication, such as a selective serotonin reuptake inhibitor (SSRI), while completing breast cancer therapy.
Cytochrome P-450 2D6 (CYP2D6) metabolizes SSRIs and also metabolizes tamoxifen to more active forms. Therefore, concurrent use of SSRIs may reduce tamoxifen’s effectiveness at preventing breast cancer recurrence.
The SSRI citalopram has limited potency to inhibit CYP2D6 activity, so has been recommended for breast cancer patients taking tamoxifen. This study provides epidemiologic evidence to support this recommendation.

Material and methods
We conducted a case-control study of breast cancer recurrence nested in the population of female residents of Denmark who were diagnosed with non-metastatic estrogen-receptor positive breast cancers between 1994 and 2001 and who took tamoxifen for at least one year. We ascertained complete prescription histories by linking cases’ and controls’ civil registration numbers to the Danish national prescription registry. We estimated the association between SSRI use while taking tamoxifen and risk of recurrent breast cancer.

Results
About the same proportion of recurrent cases (37 of 366) and matched controls (35 of 366) received at least one prescription for citalopram or its s-stereoisomer while taking tamoxifen (adjusted odds ratio = 1.1, 95% confidence interval =0.7, 1.7).
Breast cancer patients taking other SSRIs were also at no increased risk of recurrence (adjusted odds ratio = 0.9, 95% confidence interval = 0.5, 1.8 ).

Discussion
Breast cancer patients with indications for an SSRI may be prescribed citalopram — and possibly other SSRI — without adversely affecting the outcome of adjuvant therapy with tamoxifen.

The results of this study provide clinical epidemiologic support for the hypothesis that citalopram, taken concurrently with tamoxifen, does not reduce tamoxifen’s protective effect against breast cancer recurrence in early stage patients whose tumor cells express the estrogen receptor.