The use of antidepressants, especially drugs like Zoloft and Prozac, may increase the risk of abnormal bleeding, Dutch researchers report.

Although the reason for this association is unclear, it may relate to the effect these drugs have on a chemical called serotonin. Antidepressants vary in their ability to block serotonin absorption by cells. Zoloft and Prozac belong to a drug group - selective serotonin reuptake inhibitors or SSRIs - that is particularly adept at blocking absorption.

In the brain, blocking serotonin uptake can be a good thing as it may improve a patient’s mood. In the blood, however, this blockage might be a bad thing, because clotting cells called platelets need the chemical to function properly. Still, previous studies looking at whether antidepressants promote bleeding have been inconclusive.

As reported in the Archives of Internal Medicine, Dr. Eibert R. Heerdink, from the Utrecht Institute for Pharmaceutical Sciences, and colleagues performed a study involving 1168 new antidepressant users. The subjects included 196 patients who had abnormal bleeding (severe enough to require hospital admission) and 972 patients without bleeding problems.

Compared with antidepressants that had little or no effect on serotonin, those with a moderate degree of blockage nearly doubled the risk of abnormal bleeding. Some examples of drugs with this degree of blockage include amitriptyline, venlafaxine, and dothiepin.

The greatest increase in bleeding risk - 2.6-fold - occurred with drugs that provide a high degree of serotonin blockage. Although this group consists mainly of SSRIs, the highest risk was actually seen with clomipramine, a drug that belongs to a group called tricyclic antidepressants. Users of this drug were 9.4-times more likely to experience bleeding than users of antidepressants with little effect on serotonin.

The results indicate that antidepressants that block serotonin uptake, particularly SSRIs and clomipramine, may increase the risk of abnormal bleeding, the researchers conclude.

SOURCE: Archives of Internal Medicine, November 22, 2004.