Platelet and endothelial activity in comorbid major depression and coronary artery disease patients treated with citalopram: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy Trial (CREATE) biomarker sub-study.
OBJECTIVE
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).


CONCLUSIONS
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.
van Zyl
Louis T
LT
Department of Psychiatry, Queen's University, Kingston, ON, Canada.
Lespérance
Francois
F
Frasure-Smith
Nancy
N
Malinin
Alex I
AI
Atar
Dan
D
Laliberté
Marc-André
MA
Serebruany
Victor L
VL
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology* / Q000627:therapeutic use; D000077144:Clopidogrel; D015897:Comorbidity; D003327:Coronary Disease / Q000097:blood* / Q000150:complications; D003865:Major Depressive Disorder / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000628:therapy; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D019007:P-Selectin / Q000032:analysis / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011613:Psychotherapy; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult; D001620:beta-Thromboglobulin / Q000032:analysis
D000928:Antidepressive Agents; D001241:Aspirin; D015415:Biomarkers; D015283:Citalopram; D000077144:Clopidogrel; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors; D013988:Ticlopidine; D001620:beta-Thromboglobulin