title: Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies.
abstract: Selective serotonin reuptake inhibitors (SSRIs) have been reported to be potentially associated with an increased risk of bleeding. A meta-analysis of observational studies was conducted to quantify this risk. Case-control and cohort studies investigating bleeding risk under SSRI therapy were retrieved by searching the Medline, Pascal, Google Scholar and Scopus databases. Case-control studies were included if they reported bleeding incidents with and without the use of SSRIs and cohort studies were included if they reported the rate of bleeds among SSRI users and non-users. The main outcome was severe bleeding, whatever the site. Only data concerning SSRI belonging to the ATC class N06AB were used. For both case-control and cohort studies, we recorded the adjusted effect estimates and their 95% confidence intervals (CI). Pooled adjusted odds ratio (OR) estimates were computed for case-control and cohort studies using an inverse-variance model. Meta-analysis of the adjusted ORs of 42 observational studies showed a significant association between SSRI use and the risk of bleeding [OR 1.41 (95% CI 1.27-1.57), random effect model, p<0.0001]. The association was found for the 31 case-control studies (1,255,073 patients), with an increased risk of 41% of bleeding [OR 1.41 (95% CI 1.25-1.60)], as well as for the 11 cohort studies including 187,956 patients [OR 1.36 (95% CI 1.12-1.64)]. Subgroup analyses showed that the association remained constant whatever the characteristics of studies. This meta-analysis shows an increased risk of bleeding of at least 36% (from 12% to 64%) based on the high-level of observational studies with SSRIs use.
authors: INSERM, UMR 1059, SAINBIOSE, Dysfonction Vasculaire et Hémostase, Université Jean Monnet, F-42023, Saint-Etienne, France; Unité de Recherche Clinique, Innovation, Pharmacologie, CHU Saint-Etienne, Hôpital Nord, F-42055 France. Electronic address: silvy.laporte@chu-st-etienne.fr.
authors: Silvy
authors: S
authors: Laporte
authors: INSERM, UMR 1059, SAINBIOSE, Dysfonction Vasculaire et Hémostase, Université Jean Monnet, F-42023, Saint-Etienne, France; Unité de Recherche Clinique, Innovation, Pharmacologie, CHU Saint-Etienne, Hôpital Nord, F-42055 France. Electronic address: celine.chapelle@chu-st-etienne.fr.
authors: Céline
authors: C
authors: Chapelle
authors: Unité de Recherche Clinique, Innovation, Pharmacologie, CHU Saint-Etienne, Hôpital Nord, F-42055 France. Electronic address: p.caillet@yahoo.fr.
authors: Pascal
authors: P
authors: Caillet
authors: Centre Régional de Pharmacovigilance, CHU de Saint-Etienne, Hôpital Nord, F-42055, Saint-Etienne, France. Electronic address: m.noelle.beyens@chu-st-etienne.fr.
authors: Marie-Noëlle
authors: MN
authors: Beyens
authors: Centre Régional de Pharmacovigilance, CHU de Saint-Etienne, Hôpital Nord, F-42055, Saint-Etienne, France. Electronic address: florelle.bellet@chu-st-etienne.fr.
authors: Florelle
authors: F
authors: Bellet
authors: INSERM, UMR 1059, SAINBIOSE, Dysfonction Vasculaire et Hémostase, Université Jean Monnet, F-42023, Saint-Etienne, France; Laboratoire de Pharmacologie-Toxicologie, CHU de Saint-Etienne, Hôpital Nord, F-42055, Saint-Etienne, France. Electronic address: xavier.delavenne@chu-st-etienne.fr.
authors: Xavier
authors: X
authors: Delavenne
authors: INSERM, UMR 1059, SAINBIOSE, Dysfonction Vasculaire et Hémostase, Université Jean Monnet, F-42023, Saint-Etienne, France; Service de Médecine Vasculaire et Thérapeutique, CHU de Saint-Etienne, Hôpital Nord, F-42055, Saint-Etienne, France. Electronic address: patrick.mismetti@chu-st-etienne.fr.
authors: Patrick
authors: P
authors: Mismetti
authors: INSERM, UMR 1059, SAINBIOSE, Dysfonction Vasculaire et Hémostase, Université Jean Monnet, F-42023, Saint-Etienne, France; Service de Médecine Vasculaire et Thérapeutique, CHU de Saint-Etienne, Hôpital Nord, F-42055, Saint-Etienne, France; INSERM, CIC1408, F-42055, Saint-Etienne, France. Electronic address: laurent.bertoletti@chu-st-etienne.fr.
authors: Laurent
authors: L
authors: Bertoletti
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D015331:Cohort Studies; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D064887:Observational Studies as Topic; D012306:Risk; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*
chemical_list: D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Bleeding; Case-control studies; Cohort studies; Meta-analysis; Selective serotonin reuptake inhibitors