Selective serotonin reuptake inhibitors and brain hemorrhage: a meta-analysis.

OBJECTIVE We synthesized the epidemiologic evidence concerning selective serotonin reuptake inhibitor (SSRI) exposure and the risk of CNS hemorrhage. METHODS We searched for controlled observational studies comparing SSRI therapy with a control group not receiving SSRIs. We used DerSimonian and Laird fixed effect models to compute summary risk associations. RESULTS Intracranial hemorrhage was related to SSRI exposure in both unadjusted (rate ratio [RR] 1.48, 95% confidence interval [CI] 1.22-1.78) and adjusted analyses (RR 1.51, 95% CI 1.26-1.81). Intracerebral hemorrhage was also associated with SSRI exposure in both unadjusted (RR 1.68, 95% CI 1.46-1.91) and adjusted (RR 1.42, 95% CI 1.23-1.65) analyses. In a subset of 5 studies (3 of intracranial hemorrhage and 1 each reporting hemorrhagic stroke and intracerebral hemorrhage), SSRI exposure in combination with oral anticoagulants was associated with an increased risk of bleeding compared with oral anticoagulants alone (RR 1.56, 95% CI 1.33-1.83). When all studies were analyzed together, increased risk was seen across cohort studies (1.61, 95% CI 1.04-2.51), case-control studies (odds ratio [OR] 1.34, 95% CI 1.20-1.49), and case-crossover studies (OR 4.24, 95% CI 1.95-9.24). CONCLUSIONS SSRI exposure is associated with an increased risk of intracerebral and intracranial hemorrhage, yet given the rarity of this event, absolute risks are likely to be very low.