title: Trends in co-prescribing of antidepressants and tamoxifen among women with breast cancer, 2004-2010.
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.
authors.affiliation: 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. Dusetzina@unc.edu
authors.forename: Stacie B
authors.initials: SB
authors.lastname: Dusetzina
authors.forename: G Caleb
authors.initials: GC
authors.lastname: Alexander
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Freedman
authors.forename: Haiden A
authors.initials: HA
authors.lastname: Huskamp
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Keating
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003863:Depression / Q000188:drug therapy; D004347:Drug Interactions; D004348:Drug Labeling; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D057216:Propensity Score; D012189:Retrospective Studies; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000928:Antidepressive Agents; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D013629:Tamoxifen