Antidepressant Drug Compliance: Reduced Risk of MI and Mortality in Depressed Patients

Study Questions:

The long-term risk of myocardial infarction (MI) associated with use of antidepressants is uncertain, especially for non-tricyclic antidepressants. Do antidepressants increase or decrease risk of MI and all-cause mortality?


US Department of Veterans Affairs patient records were analyzed to identify a cohort free of cardiovascular disease in fiscal years 1999 and 2000, ages 25-80 years, who had an International Classification of Diseases, Ninth Revision, Clinical Modification code indicating an episode of depression (n = 93,653). Incident MI and all-cause mortality were modeled in patients who received 12 weeks or more of antidepressant pharmacotherapy, as compared with 0-11 weeks during follow-up. Age-adjusted Cox proportional hazard models were computed before and after adjusting for baseline sociodemographics and time-dependent covariates.


Receipt of 12 or more weeks of continuous antidepressant therapy was associated with significantly reduced rates of incident MI across classes of antidepressants: selective serotonin reuptake inhibitors (SSRIs) (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.44-0.52), serotonin-norepinephrine reuptake inhibitors (SNRIs) (HR, 0.35; 95% CI, 0.32-0.40), tricyclic antidepressants (TCAs) (HR, 0.39; 95% CI, 0.34-0.44), and “Other” (HR, 0.41; 95% CI, 0.37-0.45). Risk of all-cause mortality also was decreased with receipt of 12 weeks of pharmacotherapy with all classes of antidepressants (SSRI, SNRI, TCA, Other), with HRs ranging from 0.50 to 0.66.


Across classes of antidepressants, 12 weeks of pharmacotherapy appears to be safe in terms of MI risk. Although the mechanism for this association remains uncertain, it is possible that compliance with pharmacotherapy for depression reflects compliance with cardiovascular medications. It also is possible that a direct drug effect or improved depressed mood may attenuate the risk of MI in depressed patients.


The epidemiologic and biologic data linking depression with cardiovascular events is very strong. This observational study lends robust support for the safety of the major antidepressants and demonstrates a nearly 50% reduction in incident MIs and similar reduction in all-cause mortality. The National Heart, Lung, and Blood Institute and pharmaceutical industry have been reluctant to consider a placebo-controlled trial in acute coronary syndromes to see the impact of antidepressants on outcome and mortality. Perhaps this study will help move them along.

Clinical Topics: Acute Coronary Syndromes, Statins

Keywords: Myocardial Infarction, Depressive Disorder, Acute Coronary Syndrome, National Heart, Lung, and Blood Institute (U.S.), Follow-Up Studies, Serotonin, United States

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