SSRI Use Tied to Increased Risk of Intracranial Hemorrhage

Although selective serotonin reuptake inhibitors (SSRIs) are known to have a better tolerability and safety profile than older antidepressants, previous studies suggest the medications increase the risk for abnormal bleeding. A study published in February in JAMA Neurology has found that patients taking antidepressants that are strong inhibitors of serotonin reuptake may be at an increased risk for intracranial hemorrhage, particularly during the first month of use and when used concomitantly with oral anticoagulants.

Christel Renoux, M.D., Ph.D.

“Although this event is quite rare, this potential risk must be kept in mind in patients at high risk of intracranial bleeding,” including those taking anticoagulants and antiplatelet therapy, said lead author Christel Renoux, M.D., Ph.D., an assistant professor of neurology and neurosurgery at the McGill University in Canada, told Psychiatric News.

For the study, Renoux and colleagues analyzed data contained in the United Kingdom’s Clinical Practice Research Datalink, a large database of anonymized primary care medical records. Outcomes in more than 1.36 million adults who began taking SSRIs or tricyclic antidepressants for the first time between January 1, 1995, and June 30, 2014, were tracked for an average of 5.8 years. During the follow-up period, 3,036 patients were diagnosed with intracranial hemorrhage, yielding an overall incidence rate of 3.8 per 10,000 people per year.

The results showed that compared with patients taking of tricyclic antidepressants, patients being treated with SSRIs had a 17 percent increased risk of experiencing an intracranial hemorrhage. The risk was highest during the first 30 days the patients were taking the medications.

When the researchers classified the antidepressants by strength of inhibition of serotonin reuptake, they found that use of strong inhibitors was associated with a 25 percent increased risk of intracranial hemorrhage compared with weak inhibitors. Strong inhibitors included duloxetine, fluoxetine, sertraline, and clomipramine; weak inhibitors included mirtazapine, nortriptyline, and trimipramine.

Patients taking both SSRIs and anticoagulants, such as vitamin K antagonists, had a three-fold increased risk for intracranial hemorrhage compared with those taking tricyclics; however, the authors noted that this risk “did not reach statistical significance. Conversely, among patients taking antiplatelet medications, SSRI use did not increase the risk.”

“It’s important to keep in mind… that SSRIs increased the risk [for intracranial hemorrhage] slightly, not dramatically—even in those taking anticoagulants—so the absolute risk for any given individual remains low,” Peter A. Shapiro, M.D., an expert in cardiovascular disease psychiatry, who was not involved with the study, told Psychiatric News. Shapiro is also a professor of psychiatry at Columbia University Medical Center.

Nevertheless, he added, clinicians should be aware of this potential risk when educating patients about antidepressants, especially those currently using anticoagulants. ■