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Trends in co-prescribing of antidepressants and tamoxifen among women with breast cancer, 2004–2010

  • Epidemiology
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Abstract

Nearly a decade ago, researchers identified a potential interaction between tamoxifen and strong CYP2D6 inhibitors, including several frequently used antidepressants. Based on evidence available at that time, a United States Food and Drug Administration advisory committee recommended tamoxifen’s label be changed in October 2006, noting that postmenopausal women with estrogen receptor-positive breast cancer who are poor CYP2D6 metabolizers by genotype or drug interactions may be at increased risk of cancer recurrence. The impact of accumulating drug risk information on antidepressant use is unknown. We conducted a retrospective, longitudinal cohort study of 13,205 women aged 50–95 with breast cancer initiating tamoxifen between July 2004 and December 2009. We evaluated trends in strong, moderate, and weak CYP2D6-inhibitor antidepressants and tamoxifen co-prescribing and factors associated with ongoing strong inhibitor use. A propensity score matched control group (aromatase inhibitor initiators) was used to estimate changes in co-prescribing, accounting for secular trends. In each month, approximately 24 % of tamoxifen and aromatase inhibitor users were prescribed antidepressants. Among women using tamoxifen and antidepressants, 34 % used strong inhibitors between 2004 and 2006 versus 15 % in 2010. Strong inhibitor use decreased more among tamoxifen users than aromatase inhibitor users (difference-in-differences [DD] −0.09; 95 % confidence interval [CI] −0.15, −0.03). Weak inhibitor use increased among tamoxifen users from 32 % between 2004 and 2006 to 52 % in 2010, more rapidly than among aromatase inhibitor users (DD 0.15; CI 0.08, 0.23). The factor most strongly associated with strong inhibitor and tamoxifen co-prescribing after 2006 was prior strong inhibitor use (RR 4.73; CI 3.62–6.18). In conclusion, there were substantial declines in strong CYP2D6-inhibitor use among tamoxifen users following dissemination of information suggesting a potential for increased risk with co-prescribing. Whether patients and providers will continue to avoid strong inhibitor antidepressants is yet to be seen, but clinicians appear to be responsive to drug interaction risk information in this setting.

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Acknowledgments

This study was supported by the Agency for Healthcare Research and Quality (RO1 HS0189960). The funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; and preparation, review, or approval of the manuscript for publication. Dr. Dusetzina currently receives funding through a Ruth L. Kirschstein-National Research Service Award Post-Doctoral Traineeship sponsored by NIMH and Harvard Medical School, Department of Health Care Policy, Grant No. T32MH019733-17. Dr. Freedman’s effort was supported by the Susan G. Komen for the Cure Foundation. Dr. Keating’s effort was supported by the Susan G. Komen for the Cure Foundation. Dr. Alexander has served as an ad hoc member of the FDA Drug Safety and Risk Management (DSaRM) Advisory Committee and is a consultant for IMS Health. Dr. Huskamp serves as an uncompensated steering committee member of the IMS Health Services Research Network.

Conflict of interest

Dr. Alexander, Dr. Huskamp, Dr. Dusetzina, Dr. Freedman, and Dr. Keating have no conflicts of interest.

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Authors and Affiliations

  1. Division of General Medicine and Clinical Epidemiology, University of North Carolina at Chapel Hill, 5034 Old Clinic Building, CB# 7110, Chapel Hill, NC, 27599, USA

    Stacie B. Dusetzina

  2. Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Stacie B. Dusetzina

  3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    G. Caleb Alexander

  4. Department of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    G. Caleb Alexander

  5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Rachel A. Freedman

  6. Department of Health Care Policy, Harvard Medical School, Boston, MA, USA

    Haiden A. Huskamp & Nancy L. Keating

  7. Division of General Internal Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Nancy L. Keating

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  1. Stacie B. Dusetzina
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  2. G. Caleb Alexander
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  3. Rachel A. Freedman
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  4. Haiden A. Huskamp
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  5. Nancy L. Keating
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Correspondence to Stacie B. Dusetzina.

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Dusetzina, S.B., Alexander, G.C., Freedman, R.A. et al. Trends in co-prescribing of antidepressants and tamoxifen among women with breast cancer, 2004–2010. Breast Cancer Res Treat 137, 285–296 (2013). https://doi.org/10.1007/s10549-012-2330-z

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  • DOI: https://doi.org/10.1007/s10549-012-2330-z

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