What is the risk of gastrointestinal bleeding associated with selective serotonin reuptake inhibitors (SSRIs)?

Gail Woodland, Senior Information Pharmacist, Welsh Medicines Information CentreSource UKMiPublished
  • Observational study results have indicated that there is an association between the use of SSRIs and upper GI bleeds, with a number needed to harm (NNH, the number of patients who would have to receive therapy to induce one episode of upper GI bleeding) of 791.
  • The use of SSRIs with concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) has been found to increase the risk of upper GI bleeding further (NNH=160)
  • An increased risk of gastrointestinal bleeding with combined SSRI and clopidogrel/low-dose aspirin use has also been shown in studies, but conflicting evidence exists (NNH=294 for combined SSRI and antiplatelet use in one meta-analysis).
  • Being over the age of 80 or having a previous history of GI bleeding adds to the risk of upper GI bleeding with SSRIs. The risk may also be higher in patients who have just started taking SSRIs, and in those taking SSRIs with a high/intermediate affinity for the serotonin receptor.
  • If an SSRI is required in a patient at high risk of an upper GI bleed, consider the use of a gastro-protective agent. Studies have shown that acid suppressing drugs, e.g. PPIs, protect against upper GI bleeds in patients receiving single-therapy SSRI or combined NSAID and SSRI Current NICE guidance on depression recommends considering a gastroprotective drug in older people on SSRIs who are also taking NSAIDs or aspirin.
  • People taking multiple drugs that could cause bleeding should seek informed medical advice before starting regular use of non-prescription drugs such as ibuprofen.
  • Consider paracetamol as an alternative pain-killer to an NSAID in people who are taking SSRIs.