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  3. Risk of mortality with concomitant use of tamoxifen and selective serotonin reuptake inhibitors: multi-database cohort study
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Research

Risk of mortality with concomitant use of tamoxifen and selective serotonin reuptake inhibitors: multi-database cohort study

BMJ 2016; 354 doi: https://doi.org/10.1136/bmj.i5014 (Published 30 September 2016) Cite this as: BMJ 2016;354:i5014
  1. Macarius M Donneyong, research scientist1,
  2. Katsiaryna Bykov, pharmacoepidemiologist1 2,
  3. Pauline Bosco-Levy, collaborator1,
  4. Yaa-Hui Dong, visiting research fellow1,
  5. Raisa Levin, programmer collaborator1,
  6. Joshua J Gagne, assistant professor1 2
  1. 1Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA 02120
  2. 2Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA 02115
  1. Correspondence to: J J Gagne jgagne1{at}partners.org
  • Accepted 12 September 2016

Abstract

Objective To compare differences in mortality between women concomitantly treated with tamoxifen and selective serotonin reuptake inhibitors (SSRIs) that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) versus tamoxifen and other SSRIs.

Design Population based cohort study.

Setting Five US databases covering individuals enrolled in private and public health insurance programs from 1995 to 2013.

Participants Two cohorts of women who started taking tamoxifen. In cohort 1, women started taking an SSRI during tamoxifen treatment. In cohort 2, women were already taking an SSRI when they started taking tamoxifen.

Main outcome measures All cause mortality in each cohort in women taking SSRIs that are potent inhibitors of CYP2D6 (paroxetine, fluoxetine) versus other SSRIs. Propensity scores were used to match exposure groups in a variable ratio fashion. Results were measured separately for each cohort and combined hazard ratios calculated from Cox regression models across the two cohorts with random effects meta-analysis.

Results There were 6067 and 8465 new users of tamoxifen in cohorts 1 and 2, respectively. Mean age was 55. A total of 991 and 1014 deaths occurred in cohorts 1 and 2 during a median follow-up of 2.2 (interquartile range 0.9-4.5) and 2.0 (0.8-3.9) years, respectively. The pooled hazard ratio for death for potent inhibitors (rate 58.6/1000 person years) compared with other SSRIs (rate 57.9/1000 person years) across cohorts 1 and 2 was 0.96 (95% confidence interval 0.88 to 1.06). Results were consistent across sensitivity analyses.

Conclusion Concomitant use of tamoxifen and potent CYP2D6 inhibiting SSRIs versus other SSRIs was not associated with an increased risk of death.

Footnotes

  • Contributors: MMD and JJG conceived and design the study. JJG obtained the funding. All authors analyzed and interpreted data. MMD drafted the article, which was revised critically for important intellectual content by all authors, who approved the final version for publication. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. MMD and JJG are guarantors.

  • Funding: This study was funded by the Agency for Healthcare Research and Quality (R01HS023122 (JJG)). The sponsor had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: KB is supported by a training grant from Takeda through Harvard T.H. Chan School of Public Health; JJG is principal investigator of a grant from Novartis Pharmaceuticals Corporation to the Brigham and Women's Hospital for unrelated work and is a consultant to Aetion, a software company, and to Optum.

  • Ethical approval: This study was approved by the institutional review board (No 2014P000810) of the Brigham and Women’s Hospital, Boston, MA, and data use agreements were in place.

  • Data sharing: No additional data available.

  • Transparency: The lead authors affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

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