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.
Stroke Prevention and Atherosclerosis Research Centre (SPARC), Western University, London, Canada. dhackam@uwo.ca
Daniel G
DG
Hackam
Marko
M
Mrkobrada
D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000453:epidemiology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology*; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology*
D000925:Anticoagulants; D017367:Selective Serotonin Reuptake Inhibitors