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Depression both occurs frequently after stroke and increases the risk for stroke (JW Neurol Nov 1 2011), and so the use of selective serotonin reuptake inhibitors (SSRIs) is common in patients with stroke histories or at risk for stroke. Because SSRIs have been associated with gastrointestinal bleeding, there is concern that these medications might also increase risk for intracerebral bleeds.
These authors performed a meta-analysis of 16 observational studies that included an appropriate, non-SSRI control group (N=506,411 patients). A small but significant increase in intracerebral hemorrhages was seen with SSRI exposure (adjusted rate ratio, 1.42), and for intracranial hemorrhage (ARR, 1.51). Risk for subarachnoid hemorrhage did not increase. Risk with SSRIs plus oral anticoagulants (examined in 5 studies) was higher than with anticoagulants alone. Seven studies examined treatment duration; risk appeared to be limited to the first several months of treatment.
Hackam DG and Mrkobrada M. Selective serotonin reuptake inhibitors and brain hemorrhage: A meta-analysis. Neurology 2012 Oct 30; 79:1862.
McGrath ER and O'Donnell MJ. Estimating treatment effects in observational studies. Neurology 2012 Oct 30; 79:1844.
Comment
The authors estimate that the increased risk with SSRI treatment for additional intracerebral bleeding episodes would result in 1 additional intracerebral bleeding episode per 10,000 people treated for 1 year (or an increased rate from 24.6 to 34.6 per 100,000 person/years). The editorialists note that the studies may not have controlled for possibly confounding risk factors for both stroke and depression (e.g., diabetes, small vessel disease, alcoholism).
This small increase in risk should have negligible impact on most patients. The authors suggest that alternative therapies (non-SSRI antidepressants) might be appropriate for patients who are already at an increased risk for intracerebral bleeds — e.g., those on long-term anticoagulants or with severe alcohol abuse, previous intracranial bleeding, or cerebral amyloid angiopathy.