Background: The long-term risk of myocardial infarction (MI) associated with use of antidepressants is uncertain, especially for nontricyclic antidepressants. The present study uses a national Veterans Affairs cohort to test whether antidepressants increase or decrease risk of MI and all-cause mortality. Methods: US Department of Veterans Affairs patient records were analyzed to identify a cohort free of cardiovascular disease in fiscal years 1999 and 2000, aged 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. Results: 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 inhibitor (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. Conclusions: 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.
- Myocardial infarction