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


METHODS
Population based cohort study.


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


METHODS
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.


METHODS
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.


CONCLUSIONS
Concomitant use of tamoxifen and potent CYP2D6 inhibiting SSRIs versus other SSRIs was not associated with an increased risk of death.
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA 02120.
Macarius M
MM
Donneyong
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA 02120 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA 02115.
Katsiaryna
K
Bykov
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA 02120.
Pauline
P
Bosco-Levy
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA 02120.
Yaa-Hui
YH
Dong
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA 02120.
Raisa
R
Levin
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA 02120 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA 02115 jgagne1@partners.org.
Joshua J
JJ
Gagne
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality*; D008875:Middle Aged; D057216:Propensity Score; D012044:Regression Analysis; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013629:Tamoxifen / Q000627:therapeutic use*; D014481:United States / Q000453:epidemiology
D018931:Antineoplastic Agents, Hormonal; D017367:Selective Serotonin Reuptake Inhibitors; D013629:Tamoxifen
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