Antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs) may be associated with increased risk of bleeding in the stomach and intestines, according to new research.

SSRIs include Paxil, Zoloft, Prozac, Celexa, Luvox, and Lexapro.

The findings are preliminary and don't prove a direct link, say the researchers. The study also shows that the risk of bleeding associated with SSRIs was similar to the risk associated with the use of NSAIDs (nonsteroidal anti-inflammatory drugs). There are about 20 traditional NSAIDs, including aspirin, ibuprofen (Advil and Motrin), naproxen (Aleve), indomethacin (Indocin), and piroxicam (Feldene).

The study was presented in Chicago at Digestive Disease Week 2005, a meeting of experts in digestive diseases.

The study also does not pinpoint specific SSRI drugs or show the amount of gastrointestinal bleeding, say the researchers, who include Michael P. Jones, MD, of Northwestern University.


Review of Hospital Records

Jones and colleagues studied records of nearly 550 people who were hospitalized at one of three centers (Northwestern University in Chicago, Rush University in Chicago, and the Mayo Clinic in Scottsdale, Ariz.) for gastrointestinal bleeding.

Those patients were compared with 950 people of similar backgrounds who were admitted to the same hospitals on the same days but did not have gastrointestinal bleeding.

The researchers noted use of any SSRIs, NSAIDs, and other blood thinners used in patients with established heart disease.

They found that compared with people without bleeding, patients with gastrointestinal bleeding were:

—1.75 times as likely to be taking NSAIDs

—1.6 times as likely to be taking SSRIs

—1.9 times as likely to use aspirin

'Association' Noted

The association between SSRIs and gastrointestinal bleeding was "a little less" than that of NSAIDs, which are "clearly recognized" for that particular side effect, says Jones.

The study was "relatively small," larger studies are needed, and the database wasn't big enough to focus on any possible drug interactions or any particular SSRI drugs, says Jones. He also says the amount of gastrointestinal bleeding wasn't noted, but SSRIs were associated with bleeding in the upper and lower gastrointestinal tracts.

The risk is "worth realizing" and "needs to be factored in" for at-risk patients, says Jones, giving an example of a hypothetical patient using both NSAIDs and SSRIs with a medical history suggesting vulnerability to gastrointestinal bleeding. "The true magnitude needs to be determined and how to manage that needs to be determined," he says.

The study was sponsored by TAP Pharmaceuticals, the maker of Prevacid and Lupron Depot.

Link Mentioned in Prescribing Information

WebMD contacted the makers of Paxil, Zoloft, and Prozac for comment.

Morry Smulevitz, spokesman for Lilly, the maker of Prozac, told WebMD he had not seen the new study but that gastrointestinal bleeding risk is already noted in the drug's publicly available prescribing information. Lilly is a WebMD sponsor.

Prescribing information for Paxil and Zoloft has similar language. These drugs' prescribing information mainly centers on concurrent use of SSRIs with drugs such as NSAIDs or aspirin.

Patients "should be cautioned" about taking an SSRI with NSAIDs, aspirin, or other drugs that affect coagulation (blood clotting ability), says the prescribing information. While studies mainly focused on upper gastrointestinal bleeding, "there is reason to believe that bleeding at other sites may be similarly potentiated" by taking an SSRI with NSAIDs or aspirin, says the prescribing information.

Paxil is made by GlaxoSmithKline, a WebMD sponsor. Zoloft is made by Pfizer, also a WebMD sponsor.

By Miranda Hitti, reviewed by Brunilda Nazario, MD

SOURCES: Digestive Disease Week 2005, Chicago, May 14-19, 2005. Michael P. Jones, MD, Northwestern University. Morry Smulevitz, spokesman, Lilly. GlaxoSmithKline: "Prescribing Information for Paxil." Pfizer, Zoloft Prescribing Information. TAP Pharmaceutical Products.