Effect of Antidepressants and Their Relative Affinity for the Serotonin Transporter on the Risk of Myocardial Infarction

Abstract

Background-Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), attenuate platelet activation by depleting serotonin storage and may decrease risk of myocardial infarction (MI). These drugs differ in their affinity for the platelet serotonin transporter and therefore may vary in their effects on MI protection. Methods and Results-A case-control study of first MI in patients aged 40 through 75 years was conducted among 36 hospitals in a 5-county area during a 3-year period. Case subjects were patients hospitalized with a first MI, and control subjects were randomly selected from the same geographic area. Detailed information regarding medication use and other clinical and demographic data were obtained by telephone interview. Among the 1080 cases and 4256 controls who participated, there were 223 users of antidepressants with high serotonin transporter affinity, all of which were SSRIs (paroxetine, fluoxetine, and sertraline). After adjustment with multivariable logistic regression for age, gender, race, education, physical activity, quantity of cigarettes smoked per day, body mass index, aspirin use, family history of MI, and history of diabetes, hypertension, or hypercholesterolemia, the odds ratio for MI among current users of antidepressants with high serotonin transporter affinity compared with nonusers was 0.

Alteration of Decreased Plasma NO Metabolites and Platelet NO Synthase Activity by Paroxetine in Depressed Patients

“…Measurement of the endothelium-dependent flow-mediated dilation of the brachial artery with ultrasonography is one of the methods that may serve to confirm that paroxetine-induced increase in plasma NOx levels is associated with an improvement in endothelial function (Sauer et al, 2003;Faulx et al, 2003).…”

Depression and cardiovascular disease

“…Observational data also suggest that SSRIs may be associated with a reduction in MI. 18 Clearly, further studies are needed to determine whether treatment of depression, particularly with SSRIs, can improve cardiovascular outcomes.…”

Depression, cardiac mortality and all-cause mortality

“…SSRIs may have a cardioprotective effect. A case-control study of 5336 patients treated with fluoxetine, sertraline or paroxetine conferred a significantly reduced odds ratio of 0.59 for myocardial infarction (Sauer 2003). However, the literature on allcause mortality is not clear-cut, as few long-term prospective studies have been done owing to the potential complexity of ethical study designs and confounding variables.…”