title: Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs.
abstract: BACKGROUND
  Selective serotonin reuptake inhibitors (SSRIs) have been associated with upper gastrointestinal haemorrhage (UGIH) but the magnitude and characteristics of this reaction and possible interaction with concurrent Non-Steroidal Anti-Inflammatory Drug (NSAID) therapy are unknown.
  
  
  OBJECTIVE
  To evaluate systematically the risk of UGIH with SSRIs, including interaction with NSAIDs.
  
  
  METHODS
  We searched PubMED, Science Citation Index, and trial registries for data on SSRIs, NSAIDs and UGIH. We evaluated spontaneous case reports from pharmacovigilance databases.
  
  
  RESULTS
  Random effects meta-analysis of four observational studies involving 153 000 patients showed an odds ratio of 2.36 (95% CI: 1.44-3.85; P = 0.0006) for SSRI associated UGIH. The odds ratio increased to 6.33 (95% CI: 3.40-11.8; P < 0.00001) with concomitant NSAIDs. In patients aged above 50 years with no UGIH risk factors, the Number-Needed-to-Harm per year is 411 for SSRIs alone, and 106 with concomitant NSAIDs. Analysis of 101 spontaneous reports showed that UGIH occurred after a median of 25 weeks with SSRIs. Around 67% of these patients were on NSAIDs.
  
  
  CONCLUSIONS
  Selective serotonin reuptake inhibitor use, alone and in combination with NSAIDs, substantially increases the risk of UGIH. Clinicians should consider this when managing patients at risk of, or presenting with UGIH.
authors.affiliation: School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, UK. y.loke@uea.ac.uk
authors.forename: Y K
authors.initials: YK
authors.lastname: Loke
authors.forename: A N
authors.initials: AN
authors.lastname: Trivedi
authors.forename: S
authors.initials: S
authors.lastname: Singh
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D004347:Drug Interactions; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D011358:Product Surveillance, Postmarketing; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017367:Selective Serotonin Reuptake Inhibitors