title: Sertraline inhibits increases in body fat and carbohydrate dysregulation in adult female cynomolgus monkeys.
abstract: Selective serotonin reuptake inhibitor (SSRI) antidepressants are widely prescribed for depression and other disorders. SSRIs have become one of the most commonly used drugs in the United States, particularly by women. Acute effects on body composition and carbohydrate metabolism have been reported, but little is known regarding the effects of chronic SSRI use. We evaluated the effects of chronic administration of a commonly prescribed SSRI, sertraline HCl, on body weight and composition, fat distribution, carbohydrate metabolism, as well as activity, in adult female depressed and nondepressed cynomolgus monkeys (Macaca fascicularis; n=42) using a placebo-controlled, longitudinal, randomized study design. Phenotypes were evaluated prior to and after 18 months of oral sertraline (20mg/kg) or placebo. Over the 18 month treatment period, the placebo group experienced increases in body weight, body fat (visceral and subcutaneous) fasting insulin concentrations, and homeostasis model assessment of insulin resistance scores (HOMA-IR). Sertraline treatment prevented increases in body weight, fat, insulin, and HOMA-IR (all p<0.05), without significantly altering activity levels. Sertraline treatment altered adiponectin in an unusual way - reducing circulating adiponectin in depressed monkeys without affecting fat mass or body weight. Deleterious effects on adiponectin, a potentially insulin-sensitizing and atheroprotective protein, may result in adverse effects on cardiovascular health despite otherwise beneficial effects on body composition and carbohydrate metabolism.
authors.affiliation: Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, USA; Integrated Physiology and Pharmacology Graduate Program, Wake Forest School of Medicine, USA.
authors.forename: Marnie G
authors.initials: MG
authors.lastname: Silverstein-Metzler
authors.affiliation: Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Shively
authors.affiliation: Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Clarkson
authors.affiliation: Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Appt
authors.affiliation: Department of Radiology and Radiological Sciences, Vanderbilt University School of Medicine, USA.
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.affiliation: Internal Medicine/Gerontology and Geriatric Medicine, Wake Forest School of Medicine, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, USA.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Jones
authors.affiliation: Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, USA. Electronic address: register@wakehealth.edu.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage; D001823:Body Composition / Q000187:drug effects*; D001835:Body Weight; D050260:Carbohydrate Metabolism / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D007328:Insulin / Q000378:metabolism; D008137:Longitudinal Studies; D008252:Macaca fascicularis; D023421:Models, Animal; D011897:Random Allocation; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage; D020280:Sertraline / Q000008:administration & dosage*
chemical_list: D000928:Antidepressive Agents; D007328:Insulin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
keywords: Depression; Diabetes mellitus; Macaque; Metabolic syndrome; Nonhuman primate; Selective serotonin reuptake inhibitors (SSRIs)