Risk of Bleeding and Use of Antidepressants After Heart Attack

Research published in the Sept. 26, 2011, Canadian Medical Association Journal (CMAJ) found that patients prescribed a selective serotonin reuptake inhibitor (SSRI) antidepressant (such as PROZAC or PAXIL) in addition to aspirin or with aspirin plus clopidogrel (PLAVIX) after a heart attack were at a significantly increased risk of bleeding compared to people prescribed aspirin and/or clopidogrel alone.

For good reasons, patients who have experienced a heart attack will be prescribed drugs that help to prevent another one. These drugs are called antiplatelet drugs and prevent cells in the blood called platelets from clumping together to form a clot that can result in a subsequent heart attack. Two of the most common antiplatelet drugs are aspirin and clopidogrel.

An estimated 20 percent of patients also may be prescribed an antidepressant after a heart attack, because they either were on the drug before the heart attack or were thought to need the antidepressants after the heart attack. Some of the most widely prescribed antidepressants are those belonging to the SSRI family of drugs. (See Table 1 for SSRIs currently available in the U.S.)

* Do Not Use
** Limited Use (offers limited benefit or benefits certain people or conditions)

Bleeding risk and serotonin

SSRIs are thought to increase the risk of bleeding through their ability to inhibit platelets from secreting enough serotonin to help stop bleeding. Platelets are an important part of the body’s early reaction to bleeding. In response to bleeding, serotonin normally is released from platelets, causing the constriction of blood vessels and the clumping together of platelets to help stop bleeding. In the face of an inadequate amount of serotonin secretion because of SSRI use, there is an impairment of the process that stops bleeding.

Another family of antidepressants known as selective serotonin and norepinephrine reuptake inhibitors (SNRIs) also inhibits serotonin uptake by platelets and can also increase the risk of bleeding. (See Table 2 for SNRIs currently available in the U.S.)

* Do Not Use
** Limited Use (offers limited benefit or benefits certain people or conditions)
*** Do Not Use Until Seven Years After Approval (2015)

The new product labels for both SSRIs and SNRIs, which have been approved by the Food and Drug Administration (FDA), now warn of an increased risk of bleeding episodes. When members of either of these two families of antidepressants are prescribed together with aspirin, nonsteroidal anti-inflammatory drugs (such as celecoxib [CELEBREX] or ibuprofen [MOTRIN]) or anticoagulants (blood thinners, e.g., warfarin [COUMADIN]), risk of bleeding may increase.

Case reports and epidemiological studies have shown an association between the prescribing of drugs that interfere with serotonin reuptake (e.g., SSRIs and SNRIs) and episodes of gastrointestinal bleeding. The bleeding events related to SSRIs and SNRIs have ranged from bruising, nosebleeds and tiny red spots on the skin to life-threatening hemorrhages.

CMAJ study results

McGill University researchers examined the medical records of 27,058 residents of Quebec province age 50 or over who were discharged from the hospital with antiplatelet treatment following a heart attack between January 1998 and March 2007. The patients were followed until readmission to a hospital for a bleeding episode or another heart attack, death or the end of the study period.

The researchers obtained the following results:

• Compared to aspirin alone, the combined use of aspirin and an SSRI increased the risk of bleeding 1.42 times.
• Compared to aspirin alone, an aspirin-clopidogrel combination and an SSRI increased the risk of bleeding 2.35 times.
• Compared with aspirin and clopidogrel use, an SSRI-aspirin combination and clopidogrel increased the risk of bleeding 1.57 times.

The authors concluded that “Ultimately, clinicians [we would add: after a discussion with patients] must weigh the benefits of SSRI therapy against the risk of bleeding in patients with major depression following acute myocardial infarction. Clinicians should exercise caution when prescribing SSRIs to their patients with major depression following acute myocardial infarction. The potential for drug interactions must be evaluated to guide the choice of medication.”

Since the effectiveness of these drugs is well-documented for more severe forms of depression and poorly documented for milder forms of depression, consideration of the severity of depression should be an important element when deciding whether to use these drugs after a heart attack in people taking aspirin and/or clopidogrel.

What You Can Do

You and your physician should be aware that the use of antiplatelet drugs after a heart attack in combination with an SSRI antidepressant could increase the risk of bleeding. Evidence of bleeding can range from bruising, nosebleeds and tiny red spots on the skin to life-threatening hemorrhages. SNRI antidepressants may have a similar effect.

Consumers may report serious adverse events with drugs or product quality problems to the FDA’s MedWatch Adverse Event Reporting program online or by regular mail, fax or phone.

• Online: www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
• Regular mail: Use postage-paid, pre-addressed FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
• Fax: (800) FDA-0178
• Phone: (800) FDA-1088