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Bleeding increased with combined antidepressants and vitamin K antagonists
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When used to treat patients currently using vitamin K antagonists, selective serotonin reuptake inhibitors may cause nongastrointestinal bleeding, increasing the patient’s risk for hospitalization.
In a case-control study, researchers from the Netherlands analyzed data from a Dutch linkage system containing pharmacy and linked hospitalization records for nearly 2 million new users of vitamin K antagonists. Patients hospitalized for abnormal major bleeding while taking a vitamin K antagonist (n=1,848) were compared with controls.
Nongastrointestinal tract bleeding was the cause of increased risk for hospitalization in patients using selective serotonin reuptake inhibitors (OR=1.7; 95% CI, 1.1-2.5). However, those using nonsteroidal anti-inflammatory drugs had a higher risk for gastrointestinal bleeding (OR=4.6; 95% CI, 3.3-6.5). – by Stacey L. Adams
Arch Intern Med. 2008;168:180-185.
Methodologically the study was reasonable. They showed a slight increased risk for hospitalization due to bleeding in patients taking both warfarin and SSRIs. Their hypothesis seemed to be that, eventually SSRIs might have an anti-platelet effect. This is not too surprising—for a drug to have this kind of effect (increased risk for bleeding). One item they did not address was whether or not it also reduced the risk for clotting complications. Aspirin has a similar anti-platelet effect, and in some cases there is a reduction in the risk for clotting and an increased risk for bleeding simultaneously, so in a way that benefit cancels out. But, based on this study, it is unknown whether or not that would be the case.
If I were a practicing clinician, I would make sure there was an absolute need to concurrently use an SSRI with warfarin and, if it was necessary, I wouldn’t have too much hesitancy in using it. I would let patients know, as all patients on warfarin should know, to watch out for any signs of significant bleeding. And any other drugs that might have anti-platelet effects should certainly be used with caution at the same time because the risk for bleeding is slightly higher if you use a number of drugs with anti-platelet effects concurrently with warfarin.
Another item that wasn’t addressed was the international normalized ratios at the time the participants had their bleeding events. That would be an important thing to know because, in addition to anti-platelet effects, SSRIs have also been shown to inhibit some metabolizing enzymes, and it is possible that what is being shown here is simply a drug interaction with warfarin. Because INR is increased, so is the risk for bleeding. If that were the case, closer monitoring of the INR might reduce some of that risk. They have a pretty good system of monitoring warfarin therapy in the Netherlands, so I don’t suspect that it was a significant drug interaction, but it would have been nice to know the levels of anticoagulation at the time of bleeding events.
– Dan Witt, PharmD, FCCP, BCPS, CACP
Manager of Clinical Pharmacy Services, Kaiser Permanente, Aurora, Colo.