Influence of antidepressants on hemostasis

Abstract

Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are widely used for the treatment of depression and anxious disorders. The observation that depression is an independent risk factor for cardiovascular mortality and morbidity in patients with ischemic heart disease, the assessment of the central role of serotonin in pathophysiological mechanisms of depression, and reports of cases of abnormal bleeding associated with antidepressant therapy have led to investigations of the influence of antidepressants on hemostasis markers. In this review, we summarize data regarding modifications of these markers, drawn from clinical studies and case reports. We observed an association between the type of antidepressant drug and the number of abnormal bleeding case reports, with or without modifications of hemostasis markers. Drugs with the highest degree of serotonin reuptake inhibition--fluoxetine, paroxetine, and sertraline--are more frequently associated with abnormal bleeding and modifications of hemostasis markers. The most frequent hemostatic abnormalities are decreased platelet aggregability and activity, and prolongation of bleeding time. Patients with a history of coagulation disorders, especially suspected or documented thrombocytopenia or platelet disorder, should be monitored in case of prescription of any serotonin reuptake inhibitor (SRI). Platelet dysfunction, coagulation disorder, and von Willebrand disease should be sought in any case of abnormal bleeding occurring during treatment with an SRI. Also, a non-SSRI antidepressant should be favored over an SSRI or an SRI in such a context. Considering the difficulty in performing platelet aggregation tests, which are the most sensitive in SRI-associated bleeding, and the low sensitivity of hemostasis tests when performed in case of uncomplicated bleeding in the general population, establishing guidelines for the assessment of SRI-associated bleeding complications remains a challenge.

Figure 1.. Diagrammatic representation of primary hemostasis. 5-HT, serotonin; vWF, von Willebrand factor; ADP, adenosine diphosphate; βTG, β-thromboglobulin; PF4, platelet factor 4; MLC, myosine light chain; MLCK, myosine light chain kinase; PGG₂, prostaglandin G2; PGH₂, prostaglandin H₂; PIP₂ phosphatidylinositol 3,4-bisphosphate; PKC, protein kinase C; P47, pleckstrin phosphoprotein; TK, tyrosine kinase; PECAM, platelet endothelial cell adhesion molecule; DAG, diacylglycerol; COX, cyclo-oxygenase Adapted from ref 21: Colman RW, Clowes AW, George JN, et al. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Fifth ed. Philadelphia, Pa: Lippincott Williams and Wilkins; 2006. Copyright © Lippincott, Williams and Wilkins 2006.