Antonios Douros1,2,3, Matthew Ades4, Christel Renoux5,6,7. 1. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. 2. Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine, Montreal, H3T 1E2, QC, Canada. 3. Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 4. Department of Medicine, McGill University, Montreal, QC, Canada. 5. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. christel.renoux@mcgill.ca. 6. Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine, Montreal, H3T 1E2, QC, Canada. christel.renoux@mcgill.ca. 7. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada. christel.renoux@mcgill.ca.
Abstract
BACKGROUND: Observational studies have suggested an increased risk of intracranial hemorrhage (ICH) associated with selective serotonin reuptake inhibitors (SSRIs) and other antidepressants primarily inhibiting serotonin reuptake. OBJECTIVES: Our aim was to systematically review the available epidemiologic evidence regarding the risk of ICH associated with SSRIs and antidepressants inhibiting serotonin reuptake. METHODS: MEDLINE/PubMed and EMBASE were searched for all relevant articles in English, French, or German published before April 2017. Observational studies with SSRIs or any antidepressants classified by strength of serotonin reuptake inhibition as primary exposure, a comparison group, and ICH as outcome were eligible. RESULTS: Among twelve identified studies (six nested case-control, three cohort, two case-control, one case-crossover), seven assessed the risk of ICH associated with SSRIs (some also including other antidepressants primarily inhibiting serotonin reuptake), two the risk of ICH associated with inhibitors of serotonin reuptake according to the degree of reuptake inhibition, and three addressed both objectives. Four of ten studies showed an increased risk of ICH associated with SSRIs, with the two largest studies suggesting a moderate effect. Three of five studies showed an increased risk of ICH associated with strong inhibitors of serotonin reuptake. Limitations including residual confounding, inclusion of prevalent users, potentially inappropriate study designs, and lack of power may have influenced these results, especially in studies showing no association or a highly increased risk. CONCLUSION: This systematic review suggests an increased risk of ICH with antidepressants primarily inhibiting serotonin reuptake, such as SSRIs. An increased risk of ICH with strong inhibitors of serotonin reuptake compared with weak inhibitors is also possible but the available evidence is limited. Antidepressants only moderately or weakly inhibiting serotonin reuptake might be preferred in high-risk patients.
BACKGROUND: Observational studies have suggested an increased risk of intracranial hemorrhage (ICH) associated with selective serotonin reuptake inhibitors (SSRIs) and other antidepressants primarily inhibiting serotonin reuptake. OBJECTIVES: Our aim was to systematically review the available epidemiologic evidence regarding the risk of ICH associated with SSRIs and antidepressants inhibiting serotonin reuptake. METHODS: MEDLINE/PubMed and EMBASE were searched for all relevant articles in English, French, or German published before April 2017. Observational studies with SSRIs or any antidepressants classified by strength of serotonin reuptake inhibition as primary exposure, a comparison group, and ICH as outcome were eligible. RESULTS: Among twelve identified studies (six nested case-control, three cohort, two case-control, one case-crossover), seven assessed the risk of ICH associated with SSRIs (some also including other antidepressants primarily inhibiting serotonin reuptake), two the risk of ICH associated with inhibitors of serotonin reuptake according to the degree of reuptake inhibition, and three addressed both objectives. Four of ten studies showed an increased risk of ICH associated with SSRIs, with the two largest studies suggesting a moderate effect. Three of five studies showed an increased risk of ICH associated with strong inhibitors of serotonin reuptake. Limitations including residual confounding, inclusion of prevalent users, potentially inappropriate study designs, and lack of power may have influenced these results, especially in studies showing no association or a highly increased risk. CONCLUSION: This systematic review suggests an increased risk of ICH with antidepressants primarily inhibiting serotonin reuptake, such as SSRIs. An increased risk of ICH with strong inhibitors of serotonin reuptake compared with weak inhibitors is also possible but the available evidence is limited. Antidepressants only moderately or weakly inhibiting serotonin reuptake might be preferred in high-risk patients.
Authors: Jordan Kharofa; Padmini Sekar; Mary Haverbusch; Charles Moomaw; Matthew Flaherty; Brett Kissela; Joseph Broderick; Daniel Woo Journal: Stroke Date: 2007-09-27 Impact factor: 7.914
Authors: B M Verdel; P C Souverein; S D Meenks; E R Heerdink; H G M Leufkens; T C G Egberts Journal: Clin Pharmacol Ther Date: 2010-11-24 Impact factor: 6.875
Authors: Søren Bak; Ioannis Tsiropoulos; Jens Ole Kjaersgaard; Morten Andersen; Erling Mellerup; Jesper Hallas; Luis Alberto García Rodríguez; Kaare Christensen; David Gaist Journal: Stroke Date: 2002-06 Impact factor: 7.914
Authors: Marina Daskalopoulou; Julie George; Kate Walters; David P Osborn; G David Batty; Dimitris Stogiannis; Eleni Rapsomaniki; Mar Pujades-Rodriguez; Spiros Denaxas; Ruzan Udumyan; Mika Kivimaki; Harry Hemingway Journal: PLoS One Date: 2016-04-22 Impact factor: 3.240