Antidepressant use and risk of incident cardiovascular morbidity and mortality among postmenopausal women in the Women's Health Initiative study

Abstract

Background: Antidepressants are commonly prescribed medications, but their effect on cardiovascular morbidity and mortality remains unclear.

Methods: Prospective cohort study of 136 293 community-dwelling postmenopausal women in the Women's Health Initiative (WHI). Women taking no antidepressants at study entry and who had at least 1 follow-up visit were included. Cardiovascular morbidity and all-cause mortality for women with new antidepressant use at follow-up (n = 5496) were compared with those characteristics for women taking no antidepressants at follow-up (mean follow-up, 5.9 years).

Results: Antidepressant use was not associated with coronary heart disease (CHD). Selective serotonin reuptake inhibitor (SSRI) use was associated with increased stroke risk (hazard ratio [HR],1.45, [95% CI, 1.08-1.97]) and all-cause mortality (HR,1.32 [95% CI, 1.10-1.59]). Annualized rates per 1000 person-years of stroke with no antidepressant use and SSRI use were 2.99 and 4.16, respectively, and death rates were 7.79 and 12.77. Tricyclic antidepressant (TCA) use was associated with increased risk of all-cause mortality (HR,1.67 [95% CI, 1.33-2.09]; annualized rate, 14.14 deaths per 1000 person-years). There were no significant differences between SSRI and TCA use in risk of any outcomes. In analyses by stroke type, SSRI use was associated with incident hemorrhagic stroke (HR, 2.12 [95% CI, 1.10-4.07]) and fatal stroke (HR, 2.10 [95% CI, 1.15-3.81]).

Conclusions: In postmenopausal women, there were no significant differences between SSRI and TCA use in risk of CHD, stroke, or mortality. Antidepressants were not associated with risk of CHD. Tricyclic antidepressants and SSRIs may be associated with increased risk of mortality, and SSRIs with increased risk of hemorrhagic and fatal stroke, although absolute event risks are low. These findings must be weighed against quality of life and established risks of cardiovascular disease and mortality associated with untreated depression.

Figure 1.

Diagram depicting derivation of analytic cohort. AD indicates antidepressant; CT, clinical trial; DM, diabetes mellitus; HT, hypertension; OS, observational study; SSRI, selective serotonin reuptake inhibitor; and TCA, tricyclic antidepressant.

Figure 2.

Hazard ratios for coronary heart disease (CHD) (A), stroke (B), and all-cause mortality (C). All panels compare antidepressant users and nonusers stratified by depression status at baseline and first follow-up and adjusted for age, race, income, log of depression screen score at baseline and follow-up, systolic blood pressure, high cholesterol level requiring treatment with pills, hypertension treatment, smoking status, physical activity, body mass index, alcohol use, diabetes treatment, history of myocardial infarction or stroke, hormone therapy use, migraine headaches, aspirin or nonsteroidal anti-inflammatory use, and decile of propensity for any incident antidepressant use. AD indicates antidepressant; CI, confidence interval.