Antidepressant Link to Abdominal Bleeding Studied
Commonly used antidepressants such as Paxil®, Zoloft®, and Prozac® appear to be linked to an increased risk of abdominal bleeding, researchers report at Digestive Disease Week 2005, a meeting of gastroenterologists.
Experts have mixed reaction to the study's findings.
These medications belong to the class of drugs called selective serotonin reuptake inhibitors (SSRIs), which work by preventing the re-absorption of the neurotransmitter serotonin, a chemical that lets nerve cells within the brain communicate with each other.
An imbalance of serotonin appears to be an important factor in the development of depression.
Serotonin is also needed to allow normal clotting. SSRIs may block the ability of the platelets to get needed serotonin from the bloodstream, thus increasing the risk of abnormal bleeding, the researchers explain.
"We found the overall risk for gastrointestinal hemorrhage for SSRIs was almost double, compared with control subjects," says lead researcher Dr. Michael Jones, an associate professor of gastroenterology at Northwestern University.
A similar risk was found between abdominal bleeding and use of non-steroidal anti-inflammatory drugs (NSAIDS).
In the study, Dr. Jones' team looked at 917 patients. Of these individuals, 417 had abdominal bleeding and the rest did not.
Seventeen percent of those who had abdominal bleeding had used SSRIs, compared to 12 percent of those who did not. In addition, however, 17 percent of those with abdominal bleeding had used painkillers such as aspirin and other NSAIDS - including cox-2 inhibitors such as Vioxx - compared with 13 percent of those with no bleeding.
Moreover, 41 percent of the bleeders and 30 percent of the non-bleeding patients had used Plavix, which inhibits clotting. And 24 percent of the bleeders had used the blood thinner warfarin (Coumadin®), compared to 16 percent of the non-bleeders.
The researchers note that the patients with bleeding were significantly more likely to be using more than one medication associated with increased risk of abdominal bleeding.
Dr. Jones' team say their analysis confirmed previous studies that have linked SSRIs and abdominal bleeding.
"The risk appears to extend not just to bleeding in the upper GI tract, but in the lower GI tract as well," Dr. Jones explains.
One expert says the results confirm his own research on the link, which was reported in the British Medical Journal in 1999.
"I am glad to hear from this study, whose results seem consistent with others that have been published, among them, the seminal one which I wrote with my colleagues," said Dr. Francisco J. de Abajo, from the Division of Pharmacoepidemiology and Pharmacovigilance at the Spanish Agency for Medicines and Medical Devices in Madrid.
"Doctors should exercise caution when the patient has a past history of peptic ulcer, in particular if there was a gastrointestinal bleeding, and when they are treated with NSAIDs," Dr. de Abajo says. "In this later case, the less toxic NSAIDs at the lowest possible dose should be selected."
However, another expert disagrees.
"You cannot conclude from these data that SSRIs increase the risk of abdominal bleeding," says Dr. Lorrin Koran, a professor of psychiatry and behavioral science at Stanford University School of Medicine.
The reason these data appear confusing is that the persons who were bleeding were also taking other medications that cause bleeding, Dr. Koran adds.
"The only way to find out if SSRIs make a contribution would be to look at those people who were bleeding and not bleeding, who were not taking any of those drugs," he says.
Dr. Koran believes that because SSRIs affect clotting, they could theoretically increase the risk of bleeding. "But it's not a serious problem," he says.
Always consult your physician for more information.
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New research suggests a variation on one gene can disrupt a mental circuit, making people more susceptible to depression and anxiety, says a report in Nature Neuroscience.
The circuit controls the body's ability to silence a ringing alarm in the brain when a human feels fear, says study co-author Dr. Daniel R. Weinberger, director of the Genes, Cognition and Psychosis Program at the National Institute of Mental Health.
Brain scans showed that people with less effective circuitry were more likely to have trouble dealing with the stresses of life, he adds.
The findings will not immediately lead to new treatments for mental illness, Dr. Weinberger notes. In fact, antidepressants already target some related circuitry in the brain.
However, he says the research gives scientists more understanding into how people cope - and do not cope - with the slings and arrows of life.
"We're chipping away at what previously seemed like such complex human qualities," he says.
In the study, Dr. Weinberger and colleagues examined the brain scans of 114 healthy people to see the effect of having one or two copies of the short type of the gene.
Humans come with two copies of the gene, inherited from their parents. Each copy is "long" or "short."
The researchers found that those with at least one short copy of the gene had less effective circuitry in the part of the brain that controls responses to fear.
That meant they had less gray matter, fewer neurons and fewer neural connections.
"The problem is not the alarm clock, but the button you push to stop the alarm," which doesn't work correctly in those people, Dr. Weinberger says.
Researchers linked the effectiveness of the circuit to the subjects' vulnerability to depression and anxiety.
That makes sense, Dr. Weinberger explains, because in affected people "the problem isn't that you're fearful, it's that you can't stop being fearful, you can't turn it off."
But the genetic variation doesn't by itself guarantee that someone will become depressed or anxious, Weinberger said.
Other factors - both environmental and genetic - contribute to helping a person develop depression or anxiety, he said.
Dr. James Grisolia, a neurologist at Scripps Mercy Hospital in San Diego, says the study findings will need to be confirmed.
But for now, the potential link between gene variations and brain changes "underscores that tiny changes in the DNA code have the potential to cause far-reaching changes in the person."
Always consult your physician for more information.
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