Antidepressant Medication Prescription and Incident Cardiovascular Disease in Women Veterans

Objective: Antidepressants are commonly prescribed, yet understanding of consequences for cardiovascular disease (CVD) risk is less well-developed. We examined associations of antidepressants (selective serotonin reuptake inhibitors [SSRIs], serotonin norepinephrine reuptake inhibitors [SNRIs], other antidepressants) with incident CVD in women Veterans, a population with a high psychiatric and CVD risk burden.

Methods: Using Veterans Health Administration (VHA) electronic health records, we identified women Veterans who were VHA patients from January 1, 2000, to December 31, 2019. Exclusion criteria included <12 months of baseline data before index visit, prior CVD or antidepressant prescription, and no encounters after index visit. Antidepressant prescriptions were documented in pharmacy data. Our primary outcome was an incident CVD composite, comprising first-onset ischemic heart disease, stroke, atrial fibrillation/flutter, heart failure/ cardiomyopathy, and pulmonary hypertension based on diagnostic codes.

Results: Women Veterans (N = 609,546) had a mean age of 41.3 years. During mean follow-up of 8.8 years, 40.1% of women were prescribed SSRIs, 18.2% SNRIs, and 38.6% other antidepressants; 9.2% developed CVD. Marginal structural modeling was used to de-confound associations of antidepressants with incident CVD, accounting for demographics, VHA engagement, traditional CVD risk factors, and psychiatric disorders. SSRIs, SNRIs, and other antidepressants (vs no antidepressants) were associated with lower incidence of the CVD composite, as well as ischemic heart disease and stroke (relative risk: 0.27-0.76). Additionally, the inverse association between antidepressants and CVD was larger for women with major depressive disorder, posttraumatic stress disorder, and anxiety disorders.

Conclusion: As antidepressants are widely prescribed in the VHA and beyond, these results are encouraging for patients receiving this care.