Antidepressants that block action on the serotonin reuptake mechanism seem to raise the risk of upper gastrointestinal bleeding to the same degree that antiplatelet drugs do, according to data from a case-control study involving over 11,000 subjects.
Both selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) increased the risk of upper gastrointestinal bleeding, particularly when taken with NSAIDs or antiplatelet drugs, wrote Dr. Francisco J. de Abajo of the Spanish Agency for Medicines and Healthcare Products, Madrid, and his associates.
Use of acid suppressors lowered these bleeding risks, they noted.
The researchers used a large, general practice database from the United Kingdom to study whether serotonin reuptake inhibitors raise the risk of serious bleeding. They matched 1,321 cases of upper GI bleeding from erosion, peptic ulcer, or inflammation of the gastric or duodenal mucosa with 10,000 control subjects who had no GI bleeding.
The proportion of subjects currently using SSRIs (5.3%) or SNRIs (1.1%) was significantly higher in cases than in controls (3.0% and 0.3%, respectively). When SSRIs and SNRIs were combined into a single category of “serotonin reuptake inhibitors,” the odds of use of the antidepressants were nearly twice as high in cases as in controls.
The magnitude of the effect that serotonin reuptake inhibitors exerted on upper GI tract bleeding was similar to that exerted by antiplatelet agents, Dr. de Abajo and his associates said (Arch. Gen. Psychiatry 2008;65:795–803).
No significant association was found between upper GI bleeding and any other type of antidepressant. Moreover, “[we] did not identify a dose-response effect or a clear-cut duration effect in current users of SSRIs or SNRIs, although the effect was more consistent when treatment duration was longer than 3 months,” they said.
The increased risk of bleeding was further augmented by the use of NSAIDs or antiplatelet drugs. In contrast, the use of proton pump inhibitors or H2 antihistamines to suppress stomach acid “greatly reduced” the risk of GI bleeding related to serotonin reuptake inhibitors, as well as the combined effect of these drugs plus NSAIDs or antiplatelet drugs.
The researchers estimated it would be necessary to treat about 2,000 patients a year with serotonin reuptake inhibitors for 1 case of upper GI tract bleeding to be attributed to them, “indicating that the risk is rather low in the general population treated with these drugs. However, when serotonin reuptake inhibitors are combined with NSAIDs or antiplatelet drugs, the number of patients needed to be treated per year for 1 case of upper GI tract bleeding decreases remarkably [to 250–500 patients per year]. In such a high-risk population, the use of acid-suppressing agents would save a relevant number of cases and is worthwhile.”
The study was supported in part by AstraZeneca.