Selective serotonin reuptake inhibitors increase the risk of upper gastrointestinal bleeding, and the risk is increased further if the patient is also taking a non-steroidal anti-inflammatory drug, according to researchers from Spain.
They report a case control study in which the risk of bleeding was increased around threefold in patients taking SSRI antidepressants. The absolute effect was moderate, and similar to that of low dose ibuprofen. For patients taking concurrent SSRI and NSAID therapy, the risk was greater than the sum of the independent effects (British Medical Journal 1999;319:1106).
The data come from the UK general practice research database. The researchers compared antidepressant use in 1,651 patients with upper gastrointestinal bleeding and 248 patients with ulcer perforation with 10,000 matched control patients. Current exposure to SSRIs was identified in 3.1 per cent of cases and 1 per cent of controls, leading to a crude estimate of one case per 8,000 prescriptions. A smaller association was found with non-selective serotonin reuptake inhibitors (ie, drugs that inhibit both serotonin and noradrenaline reuptake). None of the antidepressants was associated with ulcer perforation.
The authors say that there is a plausible mechanism for an effect on bleeding, since depletion of platelet serotonin could impair haemostatic function.
There have been previous case reports suggesting an association between SSRIs and bleeding disorders but this is the first epidemiological study.
In an accompanying leading article (p1081), Professor Alain Li Wan Po (centre for evidence based pharmacotherapy, University of Nottingham) points out that retrospective observational studies are always subject to confounding and that further studies are needed to confirm the results. In the meantime, he suggests greater caution is "probably warranted" in co-administering NSAIDs and serotonin reuptake inhibitors, particularly for patients with risk factors for upper GI bleeding. When both classes of drugs are considered necessary, there is better evidence on the choice of an NSAID than on the choice of an antidepressant for reducing the risk of bleeding, he says.