John Jeffrey Carr
Professor of Radiology, Biomedical Informatics and Cardiovascular Medicine
Last active: 9/11/2017

Long-term sertraline treatment and depression effects on carotid artery atherosclerosis in premenopausal female primates.

Silverstein-Metzler MG, Justice JN, Appt SE, Groban L, Kitzman DW, Carr JJ, Register TC, Shively CA
Menopause. 2017 24 (10): 1175-1184

PMID: 28609387 · PMCID: PMC5607066 · DOI:10.1097/GME.0000000000000916

OBJECTIVE - Atherosclerosis developed during premenopausal years predicts postmenopausal atherosclerosis burden. Selective serotonin reuptake inhibitor (SSRI) antidepressants, recently approved for hot flushes, have been associated with increased ischemic stroke risk in several observational studies; however, effects on carotid artery atherosclerosis, a strong predictor of future vascular events, are unknown.

METHODS - The effects of chronic administration of a commonly prescribed SSRI, sertraline HCl, on atherosclerosis in the carotid artery was assessed in a placebo-controlled, longitudinal, randomized study of premeonopausal depressed and nondepressed cynomolgus monkeys (Macaca fascicularis; n = 42). Physiologic and behavioral phenotypes were evaluated at baseline and after 18 months of oral sertraline (20 mg/kg, n = 21) or placebo (n = 21). Carotid artery atherosclerosis was measured post mortem via histomorphometry.

RESULTS - Atherosclerosis extent in the right common carotid artery, on average, was 60% greater in sertraline-treated depressed monkeys compared with all other groups (P = 0.028). The results of linear regression analyses suggested that sertraline and depression effects on atherosclerosis were not mediated by their effects on behavioral and physiological risk factors.

CONCLUSIONS - These findings suggest that chronic SSRI treatment is associated with the progression of carotid artery atherosclerosis, which may increase the risk for future vascular events, particularly in depressed women. The underlying mechanism remains to be determined, but does not appear to be related to SSRI effects on traditional cardiovascular risk factors.

MeSH Terms (16)

Animals Carotid Artery, Common Carotid Artery Diseases Depression Disease Models, Animal Female Hot Flashes Humans Longitudinal Studies Macaca fascicularis Premenopause Primates Random Allocation Risk Factors Serotonin Uptake Inhibitors Sertraline

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