BACKGROUND AND PURPOSE: Major depression is an independent risk factor for increased morbidity and mortality in patients with coronary artery disease (CAD). Increased platelet activity and vascular endothelial dysfunction are possible pathways through which depression may increase cardiovascular risk. Citalopram exhibits strong selective inhibition of human platelet activation, but little is known about its effects on vascular endothelium. We assessed whether treatment of depressed CAD patients with citalopram alters platelet/endothelial biomarkers. The study was performed within the framework of the CREATE trial. METHODS: We assessed the effect of citalopram on P-selectin, beta-thromboglobulin (betaTG), soluble intercellular cell adhesion molecule-1 (sICAM-1), and total nitric oxide (tNO). Plasma samples were obtained at baseline and week 12 from subjects randomized to citalopram 20-40 mg daily (n = 36), or placebo (n = 21). Anticoagulants, aspirin, and clopidogrel were permitted. RESULTS: Treatment with citalopram was associated with greater increase in tNO over 12 weeks compared to placebo (P = 0.005). There were no differences for the other biomarkers such as P-selectin (P = 0.70), betaTG (P = 0.46) and ICAM (P = 0.59). CONCLUSION: Treatment with citalopram for 12 weeks in depressed CAD patients is associated with enhanced production of nitric oxide despite the co-administration of commonly prescribed anti-platelet regimens including aspirin and clopidogrel. Clinical implications of these findings are unclear, but improved endothelial function is implied by the increased NO production, suggesting that citalopram may be of particular benefit for patients with comorbid depression and vascular disease including CAD, stroke, peripheral artery disease, and diabetes.
RCT Entities:
BACKGROUND AND PURPOSE: Major depression is an independent risk factor for increased morbidity and mortality in patients with coronary artery disease (CAD). Increased platelet activity and vascular endothelial dysfunction are possible pathways through which depression may increase cardiovascular risk. Citalopram exhibits strong selective inhibition of human platelet activation, but little is known about its effects on vascular endothelium. We assessed whether treatment of depressed CADpatients with citalopram alters platelet/endothelial biomarkers. The study was performed within the framework of the CREATE trial. METHODS: We assessed the effect of citalopram on P-selectin, beta-thromboglobulin (betaTG), soluble intercellular cell adhesion molecule-1 (sICAM-1), and total nitric oxide (tNO). Plasma samples were obtained at baseline and week 12 from subjects randomized to citalopram 20-40 mg daily (n = 36), or placebo (n = 21). Anticoagulants, aspirin, and clopidogrel were permitted. RESULTS: Treatment with citalopram was associated with greater increase in tNO over 12 weeks compared to placebo (P = 0.005). There were no differences for the other biomarkers such as P-selectin (P = 0.70), betaTG (P = 0.46) and ICAM (P = 0.59). CONCLUSION: Treatment with citalopram for 12 weeks in depressed CADpatients is associated with enhanced production of nitric oxide despite the co-administration of commonly prescribed anti-platelet regimens including aspirin and clopidogrel. Clinical implications of these findings are unclear, but improved endothelial function is implied by the increased NO production, suggesting that citalopram may be of particular benefit for patients with comorbid depression and vascular disease including CAD, stroke, peripheral artery disease, and diabetes.
Authors: François Lespérance; Nancy Frasure-Smith; Diana Koszycki; Marc-André Laliberté; Louis T van Zyl; Brian Baker; John Robert Swenson; Kayhan Ghatavi; Beth L Abramson; Paul Dorian; Marie-Claude Guertin Journal: JAMA Date: 2007-01-24 Impact factor: 56.272
Authors: D L Musselman; A Tomer; A K Manatunga; B T Knight; M R Porter; S Kasey; U Marzec; L A Harker; C B Nemeroff Journal: Am J Psychiatry Date: 1996-10 Impact factor: 18.112
Authors: S Hess; G Baker; G Gyenes; R Tsuyuki; S Newman; Jean-Michel Le Melledo Journal: Psychopharmacology (Berl) Date: 2017-08-13 Impact factor: 4.530
Authors: Liisa Hantsoo; Kathryn A Czarkowski; Josiah Child; Christopher Howes; C Neill Epperson Journal: J Womens Health (Larchmt) Date: 2014-06-02 Impact factor: 2.681