Risk of Serious Gastrointestinal Bleeding With Newer Antidepressant Drugs

A recently published study identifies gastrointestinal (GI) bleeding as an emerging safety concern in patients taking selective serotonin reuptake inhibitor (SSRI) antidepressants, including fluoxetine (PROZAC) and paroxetine (PAXIL).

The Food and Drug Administration (FDA) has not yet required that this information be included in the Medication Guides for patients that must be dispensed with all of these drugs. The current Medication Guides warn about the possibility of increased suicidality and withdrawal reactions when suddenly stopping the drugs but have not been updated since 2007.

SSRI antidepressants block serotonin from being reabsorbed into the body’s nerve cells and elements in the blood called platelets. Serotonin, a natural chemical in the body, is needed for platelets to function properly. When levels of serotonin in platelets fall below a certain level, blood platelets are less able to clump together.

This clumping together of platelets is an extremely important part of the body’s ability to control bleeding by causing clotting. If platelets cannot clump together properly, the risk of serious bleeding is increased. Thus, when SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs) are taken, the body’s ability to control bleeding is reduced.

Although this study did not examine patients taking SNRI antidepressants, because, like SSRI antidepressants, these drugs also inhibit the reuptake of serotonin, the same reaction can be expected from these drugs as well. (See Table 1 for a list of SSRI and SNRI antidepressants currently available in the U.S.)

Test tube (or in vitro) studies offered initial evidence that SSRIs and SNRIs can interfere with platelet clumping. This finding led Danish researchers to further study the effects of these drugs in people. First, between 1995 and 2006, the researchers identified 3,652 individuals admitted to hospitals with a GI bleeding problem. Then, the researchers checked the medical records of these patients for their use of drugs to determine if there was a link between SSRI antidepressants and severe GI bleeding.

The study, published in the December 2009 Clinical Gastroenterology and Hepatology, found that current, recent (within 90 days) and past (longer than 90 days) users of SSRIs were at a 1.2- to 1.9-fold increased risk of serious GI bleeding compared to those who did not use SSRIs.

And patients who combined SSRIs with certain other widely used drugs experienced much larger increases in GI bleeding risk. Patients taking an SSRI in combination with a nonsteroidal steroidal anti-inflammatory drug (NSAID, such as celecoxib [CELEBREX] or ibuprofen [MOTRIN]) at the time of the study experienced an eight-fold increase in risk of GI bleeding, and patients taking an SSRI with both an NSAID and aspirin were at a 28-fold increased risk.

Table 2 summarizes the magnitude of the risk increases for serious GI bleeding reported in the study according to how an SSRI was used and if the SSRI was taken at the same time as an NSAID or with an NSAID plus aspirin.

Bleeding events, other than serious gastrointestinal bleeding, related to use of SSRI and SNRI that have been reported in various medical publications range from black and blue spots, bruises, nose bleeds, and localized hemorrhage to life-threatening hemorrhages.

The professional product labels or package inserts for the SSRIs and SNRIs warn prescribers that the use of these drugs with aspirin, NSAIDs and blood thinners such as warfarin (COUMADIN) may increase the risk of bleeding.

What You Can Do

Patients taking SSRI or SNRI antidepressants with other drugs should consult with their primary physician or pharmacist to make sure that the combination does not increase the risk of serious GI bleeding.

Do not discontinue using any blood thinner without consulting the prescriber.

Do not discontinue using either an SSRI or SNRI antidepressant without consulting the prescriber. Abruptly stopping these drugs can cause a withdrawal reaction.

Antidepressant drugs are among a growing list of products that are required to be dispensed with an FDA-approved Medication Guide written specifically for consumers in nontechnical language. The FDA may require Medication Guides for drugs that present serious public health concerns. Patients should read the Medication Guide for the SSRI and SNRI antidepressants they take with each new prescription, because the information may have been updated between refills.

The Medication Guides for SSRI and SNRI antidepressants include FDA black box safety warnings because these drugs can increase suicidal thoughts in children, adolescents and young adults. Another black box warns about withdrawal symptoms upon discontinuation of these drugs. As mentioned above, however, the Medication Guides do not currently warn about the risk of gastrointestinal bleeding.

The Medication Guides for the antidepressant drugs can be obtained from any pharmacist or on the FDA’s Web site: www.fda.gov/Drugs/DrugSafety/ucm085729.htm.

Table 1. Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) Available in the U.S.

* Do Not Use on WorstPills.org
** Limited Use on WorstPills.org
*** Do Not Use Until Seven Years After Approval on WorstPills.org

Table 2. Summary of Study Results