The Mortality and Myocardial Effects of Antidepressants Are Moderated by Preexisting Cardiovascular Disease: A Meta-Analysis

Abstract

Background: Antidepressants (ADs) are commonly prescribed medications, but their long-term health effects are debated. ADs disrupt multiple adaptive processes regulated by evolutionarily ancient biochemicals, potentially increasing mortality. However, many ADs also have anticlotting properties that can be efficacious in treating cardiovascular disease. We conducted a meta-analysis assessing the effects of ADs on all-cause mortality and cardiovascular events in general-population and cardiovascular-patient samples. Methods: Two reviewers independently assessed articles from PubMed, EMBASE, and Google Scholar for AD-related mortality controlling for depression and other comorbidities. From these articles, we extracted information about cardiovascular events, cardiovascular risk status, and AD class. We conducted mixed-effect meta-analyses testing sample type and AD class as moderators of all-cause mortality and new cardiovascular events. Results: Seventeen studies met our search criteria. Sample type consistently moderated health risks. In general-population samples, AD use increased the risks of mortality (HR = 1.33, 95% CI: 1.14-1.55) and new cardiovascular events (HR = 1.14, 95% CI: 1.08-1.21). In cardiovascular patients, AD use did not significantly affect risks. AD class also moderated mortality, but the serotonin reuptake inhibitors were not significantly different from tricyclic ADs (TCAs) (HR = 1.10, 95% CI: 0.93-1.31, p = 0.27). Only “other ADs” were differentiable from TCAs (HR = 1.35, 95% CI: 1.08-1.69). Mortality risk estimates increased when we analyzed the subset of studies controlling for premedication depression, suggesting the absence of confounding by indication. Conclusions: The results support the hypothesis that ADs are harmful in the general population but less harmful in cardiovascular patients.

Are Antidepressants Harmful in the “General Population”?

“…In the meta-analysis conducted by Maslej et al [1] the authors assessed the all-cause mortality hazard ratio (HR) of antidepressant (AD) use. Overall, AD use did not significantly impact all-cause mortality (HR = 1.09, p = 0.43).…”

Reply

“…We are grateful for the interest shown by Rosenblat et al [1] in our meta-analysis [2]. They question its primary results: antidepressant (AD) use is associated with a 33% increased risk of death in “general population” samples, while this risk is significantly lower in “cardiovascular” samples.…”

“…As we discussed [2, pp. 269–270], our a priori decision to stratify was based on our previous work [3]: (i) in addition to other physiological effects, many ADs have anti-clotting properties; (ii) this effect may normalize clotting function in patients with hyperactivated pro-aggregatory processes (e.g., many cardiovascular diseases); and (iii) this effect may be harmful in people with otherwise normal clotting processes.…”

“…However, we could not identify studies that had specifically screened out individuals with pro-aggregatory diseases. So, we included in this class studies involving community samples, reasoning that although some individuals in these studies might have pro-aggregatory diseases, most would not [2, p. 278]. We believe “general population” is more suitable than other labels that would definitely indicate the absence of cardiovascular disease (e.g., “non-cardiovascular samples”).…”

“…We believe “general population” is more suitable than other labels that would definitely indicate the absence of cardiovascular disease (e.g., “non-cardiovascular samples”). Since these studies predominantly involved older adults, we suggested that “our findings may not generalize to younger populations” [2, p. 278].…”