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The impact of selective serotonin reuptake inhibitors on the risk of intracranial haemorrhage: A systematic review and meta-analysis

Jensen, MP; Ziff, OJ; Banerjee, G; Ambler, G; Werring, DJ; (2019) The impact of selective serotonin reuptake inhibitors on the risk of intracranial haemorrhage: A systematic review and meta-analysis. European Stroke Journal , 4 (2) pp. 144-152. 10.1177/2396987319827211. Green open access

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Abstract

Introduction: Observational studies have suggested increased risk of intracranial haemorrhage (ICrH) in patients receiving selective serotonin reuptake inhibitors (SSRIs). We sought to clarify the impact of SSRIs on ICrH, accounting for study methodology. Patients and methods: A comprehensive search of Medline, Embase and the Cochrane Library from 1960 to December 2017 identified studies comparing SSRIs with control. The outcomes (first-ever and recurrent ICrH) were meta-analysed using a random effects model. Results: Twenty-four observational studies and three randomised trials were available for meta-analysis, totalling 4,844,090 patient-years of follow-up. Those receiving SSRIs were more likely to be female (p = 0.01) and have depression (p < 0.001). Compared to controls, SSRI users had a significantly increased risk of ICrH (relative risk (RR) 1.26, 95%CI 1.11–1.42). Although SSRI use was associated with increased ICrH risk in those without previous ICrH (RR 1.31, 95%CI 1.15–1.48), this was not the case in those with previous ICrH (RR 0.95, 95%CI 0.83–1.09). Sensitivity analysis according to the bleeding definition reported demonstrated that although ‘haemorrhagic stroke’ was associated with SSRIs (RR 1.40, 95%CI 1.13–1.72), intracerebral haemorrhage was not (RR 1.11, 95%CI 0.86–1.42). Additional sensitivity analyses demonstrated a stronger association between SSRIs and ICrH in studies with a high (p < 0.001) compared to low risk of bias (p = 0.09) and with retrospective (p < 0.001) compared to prospective (p=0.31) study designs. Discussion: Although SSRIs are associated with an increased risk of ICrH, the association is partly accounted for by important biases and other methodological limitations in the available observational data. Conclusion: Our findings suggest there is insufficient high-quality data to advise restriction of SSRIs because of concern regarding ICrH risk.

Type: Article
Title: The impact of selective serotonin reuptake inhibitors on the risk of intracranial haemorrhage: A systematic review and meta-analysis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/2396987319827211
Publisher version: https://doi.org/10.1177/2396987319827211
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Selective serotonin reuptake inhibitor, intracranial haemorrhage, haemorrhagic stroke, meta-analysis, systematic review
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Statistical Science
URI: https://discovery.ucl.ac.uk/id/eprint/10069595
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