The antidepressants are known as selective serotonin reuptake inhibitors (SSRIs), and include widely used drugs like fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa) and paroxetine (Paxil).

SSRIs have been linked to a risk of stomach bleeding. But studies have come to conflicting findings on whether SSRI users have any higher risk of hemorrhagic strokes, which happen when there is bleeding in or around the brain.

So for the new study, researchers pooled the findings from 16 past studies involving more than 500,000 people who were on SSRIs or not.

Overall, antidepressant users were about 40 to 50 percent more likely to suffer bleeding in or around the brain, the researchers report in the journal Neurology.

While those numbers might sound big, the risks to any one person would be "extremely low," said lead researcher Dr. Daniel G. Hackam, an associate professor of medicine at Western University in London, Ontario, Canada.

Based on these figures, he said, there would be one brain hemorrhage for every 10,000 people using an SSRI over one year.

What's more, the findings do not prove that the antidepressants directly cause brain bleeds. It's possible, Hackam said, that SSRI users are "sicker" than non-users or have habits that put them at greater stroke risk.

The researchers tried to account for those factors in their calculations. But some of the studies they analyzed lacked key information - like people's smoking and drinking habits, and whether they had diabetes.

"We can't infer cause and effect from this," Hackam said.

On the other hand, he added, there are reasons to believe it's the medications themselves. For one, the hemorrhage risk seemed greatest in the first months after people starting using an SSRI.

There's also a biological argument. SSRIs seem to make it harder for blood cells called platelets to clump together and form clots. And there can be a big drop in a person's platelet function in the first weeks after starting an SSRI, Hackam noted.

Still, he stressed that people on the antidepressants should not be alarmed. "I think that overall, these medications are quite safe," Hackam said.

He added that people who are already at increased risk of a brain hemorrhage may need to be careful. That includes people who've had a brain bleed in the past, or are on medications that reduce blood clotting such as warfarin (Coumadin), or a combination of aspirin and clopidogrel (Plavix).

If they need an antidepressant, Hackam suggested they talk with their doctor about trying a non-SSRI drug.

An editorial published with the study makes a similar point.

The overall risk is "very small for the average patient," write Emer R. McGrath and Martin J. O'Donnell of the National University of Ireland in Galway.

But, they add, "these findings emphasize the importance of appropriate patient selection and avoidance of inappropriate prescribing, which assumes particular importance in patients at increased risk of (brain hemorrhage)."

SOURCE: bit.ly/Q5TNl Neurology, online October 17, 2012.

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