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Selective Serotonin Reuptake Inhibitors (SSRI)

4.11 Haemorrhage, particularly gastrointestinal

Rare and very rare, but potentially serious adverse effects

By reducing the uptake of serotonin by platelets, SSRIs reduce the ability of platelets to aggregate and thereby increase the risk of haemorrhage, particularly gastrointestinal bleeding.

Factors which increase risk

Co-administration of SSRIs with other drugs associated with the risk of bleeding (eg NSAIDs and antiplatelet1 drugs such as aspirin and clopidogrel, corticosteroids, and warfarin) significantly increases the risk of gastrointestinal haemorrhage. Patients with a history of peptic ulcers and the elderly are also at higher risk of bleeding. Excessive use of alcohol may also increase the risk of gastrointestinal haemorrhage.

Risk-reduction measures

There is little justification for routine prescribing of gastroprotective treatment for patients on an SSRI with no other risk for gastrointestinal bleeding. However, individuals at higher risk of bleeding or those taking antiplatelet medicines or NSAIDs can be protected with a proton pump inhibitor2 or a histamine H2 antagonist3.


  1. Antiplatelet medicines are used to prevent heart attacks and strokes. They prevent platelets from clumping together, which, in turn, helps to prevent the formation of clots. Antiplatelet medicines include aspirin, clopidogrel, dipyridamole, and prasugrel.
  2. Proton pump inhibitors reduce the secretion of acid in the stomach; they are used to prevent and heal duodenal and gastric ulcers and to manage other conditions aggravated by stomach acid. Examples of this class of medicine include esomeprazole, lansoprazole, and omeprazole.
  3. Histamine H2 antagonists reduce the secretion of acid in the stomach. They are used to prevent and heal duodenal and gastric ulcers and to manage other conditions aggravated by stomach acid. Examples of this class of medicine include cimetidine and ranitidine.