Common Antidepressant Use Doubles Risk of Gastrointestinal Bleeding

< Oct. 10, 2007 > -- Many Americans currently take antidepressants known as SSRIs (selective serotonin reuptake inhibitors) for the treatment of depression and anxiety disorders.

New research shows that taking these medications may double the risk of gastrointestinal bleeding, according to researchers from Wake Forest University School of Medicine and colleagues. Gastrointestinal (GI) bleeding refers to any bleeding that starts in the GI tract and occurs anywhere from the mouth to the stomach or the large intestine. When the medications are taken with aspirin and other similar pain medications, the risk is more than 600 percent higher.

Prescribing Clinicians Should Consider Risks

“Clinicians who prescribe these medications should be aware of the potential risk and may need to consider alternatives,” says Dr. Sonal Singh, senior researcher and an assistant professor of internal medicine. “In addition, regulatory authorities should consider revising existing package inserts to highlight the magnitude of the risk.”

The research was reported online this month in the journal Alimentary Pharmacology & Therapeutics. Emerging evidence has shown that SSRIs may be associated with bleeding of the lining of the digestive tract including the esophagus, stomach or upper part of the small intestine, which together are called the upper gastrointestinal (GI) tract. Upper gastrointestinal bleeding may be potentially serious and require hospitalization for blood transfusions and other treatments.

The drugs are widely used to treat depression, panic disorder, and obsessive-compulsive disorder (OCD). The researchers undertook the study because of a lack of information on the exact scope of the risk.

They also looked at the effects of taking SSRIs at the same time as non-steroidal anti-inflammatory drugs (NSAIDs), which are also associated with upper GI bleeding. NSAIDs include prescription medications such as Celebrex® and over-the-counter drugs such as aspirin and Aleve®.

Combined Use of Medicines Can Create Even More Effect

The researchers pooled data from four studies involving 153,000 patients, which allowed them to detect effects that might not show up in the individual studies. They found patients taking SSRIs were nearly twice as likely to develop upper GI bleeding than patients not taking the medications.

When the patients also took NSAIDs, the risk of upper gastrointestinal bleeding was six times higher than in patients taking neither medication.

The authors say the combined use of NSAIDs and SSRIs may have a synergistic effect, which results in the elevated risk of bleeding beyond that seen with each agent alone.

“While the risk to an individual may increase by only a small amount, the impact to the general population is likely to be substantial because of the large numbers of people who use these drugs,” says Dr.Singh.

He also states that depressed, older adults may be most vulnerable because they are more likely to have conditions such as osteoarthritis that require the use of NSAIDs.

Based on their findings, the authors estimate that for every 411 patients over age 50 taking SSRIs, one is likely to develop upper GI bleeding requiring hospital admission. In patients taking both SSRIs and NSAIDs, one out of 82 would be expected to develop the problem.

“We estimate that roughly 18,000 additional cases of upper GI bleeding occurred in the United States and United Kingdom in 2003 as a result of taking SSRIs,” says Dr. Singh.

How do you know if you have gastrointestinal bleeding? According to the National Institutes of Health (NIH), you should contact your doctor if you have the following signs:

• black, tarry stools

• blood in your stool

• vomiting blood or liquid that looks like coffee grounds

Time on Medication Also a Factor

In addition to the clinical studies, the researchers analyzed 101 reports on adverse effects submitted to the Canadian Adverse Events Database and the US Food and Drug Administration’s Adverse Event Reporting System. They found that bleeding associated with SSRI use occurred after a median of 25 weeks on the medications. About 67 percent of those patients were also taking NSAIDs. The adverse reaction was not limited to the elderly, with 38 percent of cases occurring in patients below the age of 60.

“These findings emphasize the importance of clinicians taking a detailed gastrointestinal history from patients and targeting the use of SSRIs to patients who are at relatively low risk for upper GI bleeding,” says Dr. Singh.

Unsure About Specific Drugs' Interaction

The research did not distinguish between specific medications and whether one was associated with more bleeding than another. However, previous studies have shown that paroxetine (Paxil®), sertraline (Zoloft®), and fluoxetine (Prozac®) are most often associated with abnormal bleeding.

Dr. Singh says future research should address the question of which specific medications and combinations of medications are associated with the highest risk.

Always consult your physician for more information.

What is major depression?

Depression is a depressive disorder that involves a person's body, mood, and thoughts. It can affect and disrupt eating, sleeping, or thinking patterns. It is not the same as being unhappy or in a "blue" mood, nor is it a sign of personal weakness or a condition that can be willed or wished away.

People with a depressive illness cannot merely "pull themselves together" and get better. Treatment is often necessary and many times crucial to recovery.

The following are the most common symptoms of major depression. However, each individual may experience symptoms differently. Symptoms may include:

• persistent sad, anxious, or empty mood

• loss of interest in activities once previously enjoyed

• excessive crying

• increased restlessness and irritability

• decreased ability to concentrate and make decisions

• decreased energy thoughts of death or suicide, or suicide attempts

• increased feelings of guilt, helplessness, and/or hopelessness

• weight and/or appetite changes due to over- or under-eating

• changes in sleep patterns

• social withdrawal

• physical symptoms unrealized by standard treatment (i.e., chronic pain, headaches)

For a diagnosis of major depression to be made, an individual must exhibit five or more of these symptoms during the same two-week period. The symptoms of major depression may resemble other psychiatric conditions. Always consult your physician for a diagnosis.

According to the National Institute for Mental Health (NIMH), a doctor chooses an antidepressant based on the person's symptoms. Some people notice improvement in their symptoms within a couple weeks, but usually the medication must be taken regularly for at least six to eight weeks for the full therapeutic effect to occur.

Antidepressant medication should not be discontinued without discussing this with your physician first. Often the dose will be tapered down slowly, in order not to have uncomfortable side effects.

If depression is a recurrent problem, you may need to stay on medication for a period of years.

Over the past several years, SSRIs have been used instead of traditional antidepressants because they usually have fewer side effects.

Here are some side effects you might expect if you are taking an SSRI:

• sexual problems

• headache nausea 

• nervousness and insomnia

• feeling jittery

Almost all of these symptoms decrease in severity or disappear with time. Some of them can be reversed with your physician's help. Talk with your physician about any troublesome, ongoing symptoms.

Some common SSRIs are: Celexa®(citalopram), Lexapro®(escitalopram), Luvox®  (fluvoxamine), Paxil® (paroxetine), Prozac® (fluoxetine), Zoloft® (sertraline), and Serzone®  (nefazodone).

Always consult your physician for more information.