SSRIs are the most commonly used antidepressants. They are known to increase the risk of GI bleeding.Do they cause Brain bleeding as well? Studies so far show inconsistent results.
This review analysed all observational studies (prospective cohorts, retrospective cohorts, case- crossover studies, and case-control designs).Studies had to include a control group not receiving SSRI therapy. They focused on observational studies because clinical trials of antidepressant medications rarely report intracranial hemorrhagic events. The review retrieved 2,493 citations of which 16 articles were eligible for inclusion, comprising 506,411 subjects.
1. Intracranial haemorrhage was related to SSRI exposure in both unadjusted (rate ratio [RR] 1.48, 95% CI, 1.22 to 1.78) and adjusted analyses (1.51; 1.26 to 1.81). (adjusted analysis is to accommodate the various covariates like age sex, use of other medications etc)
2.Intracerebral haemorrhage was also associated with SSRI exposure in both unadjusted (1.68; 1.46 to 1.91) and adjusted (1.42; 1.23 to 1.65) analyses.
3.Subarachnoid hemorrhage was not increased in either unadjusted (RR 1.02, 95% CI 0.77–1.34) or adjusted (RR 0.62, 95%CI 0.38– 1.01) analyses.
4. In a subset of 5 studies, SSRI exposure in combination with oral anticoagulants was associated with an increased risk of bleeding compared with oral anticoagulants alone (1.56; 1.33 to 1.83).
5. When all studies were analysed together, increased risk was seen across cohort studies (1.61; 1.04 to 2.51), case-control studies (odds ratio [OR] 1.34; 1.20 to 1.49), and case-crossover studies (OR 4.24; 1.95 to 9.24).
6.Short-term, recent exposure was more strongly associated with hemorrhagic events than long-term exposure.May be because the platelet function may improve with prolonged exposure.
7. Rates of bleeds likely be higher in patients with a past history of intracerebral hemorrhage.
Limitations: Large range of sample sizes between included reports resulting in some studies having a greater likelihood of predominating in pooled analyses. Variables such as hypertension were defined somewhat differently between reports, with a lack of direct physiologic data for blood pressure, cholesterol, or renal function etc.
Clinical Practice: SSRI exposure is associated with an increased risk of intracerebral and intracranial hemorrhage though given the rarity of this event the absolute risks are likely to be very low. ( ie one additional intracerebral bleeding episode per 10,000 persons treated for 1 year could be expected). Cautious prescribing is essential especially in patients at risk of increased bleeding.
summary of the article:
Hackam DG, Mrkobrada M. Neurology. 2012 Oct 17. [Epub ahead of print]