Marnie G Silverstein-Metzler1, Jamie N Justice, Susan E Appt, Leanne Groban, Dalane W Kitzman, John Jeffrey Carr, Thomas C Register, Carol A Shively. 1. 1Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 2Integrated Physiology and Pharmacology Graduate Program, Wake Forest School of Medicine, Winston-Salem, NC 3Internal Medicine/Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC 4Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC 5Department of Internal Medicine/Cardiology, Wake Forest School of Medicine, Winston-Salem, NC 6Department of Radiology and Radiological Sciences, Vanderbilt University School of Medicine, Nashville, TN.
Abstract
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.
RCT Entities:
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.
Authors: H C McGill; C A McMahan; A W Zieske; G D Sloop; J V Walcott; D A Troxclair; G T Malcom; R E Tracy; M C Oalmann; J P Strong Journal: Arterioscler Thromb Vasc Biol Date: 2000-08 Impact factor: 8.311
Authors: Andrew D Mackinnon; Paula Jerrard-Dunne; Matthias Sitzer; Alexandra Buehler; Stefan von Kegler; Hugh S Markus Journal: Stroke Date: 2004-07-08 Impact factor: 7.914
Authors: Carol A Shively; Thomas C Register; David P Friedman; Timothy M Morgan; Jalonda Thompson; Tasha Lanier Journal: Biol Psychol Date: 2005-01-07 Impact factor: 3.251
Authors: Jordan W Smoller; Matthew Allison; Barbara B Cochrane; J David Curb; Roy H Perlis; Jennifer G Robinson; Milagros C Rosal; Nanette K Wenger; Sylvia Wassertheil-Smoller Journal: Arch Intern Med Date: 2009-12-14
Authors: A R Folsom; J H Eckfeldt; S Weitzman; J Ma; L E Chambless; R W Barnes; K B Cram; R G Hutchinson Journal: Stroke Date: 1994-01 Impact factor: 7.914
Authors: Jamie N Justice; Marnie G Silverstein-Metzler; Beth Uberseder; Susan E Appt; Thomas B Clarkson; Thomas C Register; Stephen B Kritchevsky; Carol A Shively Journal: Geroscience Date: 2017-10-28 Impact factor: 7.713