Selective serotonin reuptake inhibitors (SSRIs) appear to increase risk of upper gastrointestinal tract bleeding, with level of risk dependent on whether medications taken concurrently tend to irritate or protect the stomach, according to an article in the July issue of Archives of General Psychiatry.

Specifically, effects appear to be further increased when antidepressants are combined with medications such as non-steroidal anti-inflammatory drugs and decreased when taken with acid-suppressing agents.

Since the early 1990s, case reports have suggested an association between the antidepressants and bleeding in the upper gastrointestinal (GI) tract, according to background information in the article.

"The wide use of this drug class requires research to provide more accurate risk estimates, to identify factors that may further increase the risk and, in particular, to determine whether using acid-suppressing agents may reduce the risk," the authors wrote. "It is also important to determine whether venlafaxine hydrochloride, a new antidepressant related to SSRIs, also increases the risk of bleeding, as some individual case reports have suggested."

Francisco J. de Abajo, MD, MPH, PhD, of the Spanish Agency for Medicines and Healthcare Products, and Luis A. Garcia-Rodriguez, MD, MSc, of the Spanish Centre for Pharmacoepidemiologic Research, Madrid, Spain, studied 1,321 patients who had been referred to a specialist or hospitalized for upper GI bleeding between 2001 and 2005. These cases were compared with 10,000 control subjects who were matched for age and sex but did not have bleeding.

Individuals who had bleeding were significantly more likely than controls to be taking SSRIs (5.3 percent versus 3.0 percent) or venlafaxine (1.1 percent versus 0.3 percent). Risk of bleeding appeared to be increased further among those taking both an antidepressant and other drugs known to be harmful to the GI tract, including non-steroidal anti-inflammatory drugs and corticosteroids. Acid-suppressing agents, however, were associated with a reduced risk of bleeding in patients taking SSRIs or venlafaxine.

The researchers estimated that in patients not taking acid-suppressing agents, one individual per year would develop upper GI tract bleeding for every 2,000 patients taking these antidepressants.

"When both serotonin reuptake inhibitors [SSRIs and venlafaxine] and nonsteroidal anti-inflammatory drugs are concomitantly used, it would be sufficient to treat 250 patients per year for one case of upper GI tract bleeding to be attributed to the combination, and 500 patients per year if serotonin reuptake inhibitors are concomitantly used with antiplatelet drugs," the authors wrote.