SSRIs associated with increase in brain hemorrhage risk in some patients, but absolute risks appear small

Selective serotonin reuptake inhibitors (SSRIs) may increase risk for brain hemorrhage in some patients, although the absolute risks are probably low, a new study has reported.

Researchers performed a systematic review and meta-analysis of data from controlled observational studies to determine the risk for brain hemorrhage associated with SSRIs. Studies that compared patients receiving SSRIs with those not receiving SSRIs were included. Hemorrhages were categorized as any intracranial hemorrhage (ICH), hemorrhagic stroke (a composite of intracerebral hemorrhage and subarachnoid hemorrhage), intracerebral hemorrhage alone, and subarachnoid hemorrhage alone.

Results were published online Oct. 17 by Neurology.

A total of 16 studies were included in the analysis. In unadjusted and adjusted analyses, the data showed an association between SSRI use and ICH (rate ratios [RRs], 1.48 [95% CI, 1.22 to 1.78] and 1.51 [95% CI, 1.26 to 1.81], respectively) as well as intracerebral hemorrhage (RRs, 1.68 [95% CI, 1.46 to 1.91] and 1.42 [95% CI, 1.23 to 1.65], respectively). An association with increased risk of bleeding was also seen among patients taking SSRIs plus oral anticoagulants compared with oral anticoagulants alone in a subset of five trials, three involving ICH, one involving hemorrhagic stroke, and one involving intracerebral hemorrhage. Increased odds ratios were also observed by study type: cohort studies, 1.61 (95% CI, 1.33 to 1.83); case-control studies, 1.34 (95% CI, 1.20 to 1.49); and case-crossover studies, 4.24 (95% CI, 1.95 to 9.24).

The authors pointed out that their analysis lacked data on intracerebral hemorrhage subtype and that the included studies used different definitions for some variables, among other limitations. They concluded that SSRI use is associated with increased risk for both intracerebral hemorrhage and ICH and that physicians may want to consider other types of antidepressants in patients who have “intrinsic risk factors,” such as previous intracranial bleeding. However, they noted that the absolute risk for brain hemorrhage associated with SSRI use is probably very low.

The authors of an accompanying editorial agreed with the study's results. “For patients with a clear indication for SSRI use, the absolute increase in risk of ICH should not deter clinicians from prescribing these agents,” the editorialists wrote. “However, these findings emphasize the importance of appropriate patient selection and avoidance of inappropriate prescribing, which assumes particular importance in patients at increased risk of ICH.”