To further explore the risk of combining treatment with these drugs, the research team at Utrecht University used a database containing medication histories for more than 2 million residents of the Netherlands beginning in 1985, linked to hospital admission records.

The researchers identified 1,848 patients who were hospitalized for hemorrhage while taking a coumarin-type drug -- either acenocoumarol or phenprocoumon -- with whom they matched 5,818 non-hospitalized subjects also taking a coumarin.

Use of SSRIs -- sertraline, paroxetine, fluoxetine, fluvoxamine, escitalopram or citalopram -- raised the risk of hospitalization due to bleeding outside the gastrointestinal tract, but had no effect on hospitalization due to bleeding within the tract.

The risk for non-gastrointestinal bleeding was on a par with that posed by combined treatment with NSAID drugs, like ibuprofen. However, unlike SSRIs, NSAIDs also raised the risk of gastrointestinal bleeding among coumarin users.

The investigators observed no increased risk of bleeding associated with the non-SSRI antidepressants nortriptyline and mirtazapine.

Following discontinuation of either SSRIs or NSAIDs, the risk of major non-gastrointestinal bleeding was immediately attenuated, the authors note.

"Given the limitations of our study, we cannot advise against concurrent use of SSRIs and coumarin anticoagulants," Schalekamp's group writes. "However, intensified monitoring of users of SSRIs seems justified."

One option to reduce risk of bleeding in patients treated with a coumarin is to use a different class of antidepressant when treatment for depression is necessary, they add.

SOURCE: Archives of Internal Medicine, January 28, 2008.

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