SSRIs Up Risk of Brain Hemorrhage, but Absolute Risk Is Low

Megan Brooks

October 17, 2012

A meta-analysis of relevant research shows that treatment with a serotonin reuptake inhibitor (SSRI) is associated with an increased risk for brain hemorrhage but that the absolute risk is low.

Nonetheless, "clinicians who treat patients at high risk for intracranial hemorrhage (ICH) should probably use a different class of antidepressants, which do not modulate the serotonin pathway," Daniel G. Hackam, MD, PhD, from the Stroke Prevention and Atherosclerosis Research Centre, Western University in London, Ontario, Canada, told Medscape Medical News.

"Such patients include those on oral anticoagulants, patients with a history of alcoholism or chronic liver disease, and patients who have had a previous hemorrhagic stroke," he said.

The meta-analysis was published online October 17 in Neurology.

"Best Current Evidence"

The authors of a linked commentary congratulate the authors for their "thorough review of the evidence and succinct summary of findings."

Emer R. McGrath, MB, and Martin J. O'Donnell, MB, PhD, from the National University of Ireland in Galway, say the analysis represents "best current evidence of an association between SSRI use and risk of ICH."

Dr. Hackam and colleagues synthesized the epidemiologic evidence concerning SSRI exposure and the risk for central nervous system (CNS) hemorrhage. They reviewed and pooled data from 16 observational studies (cohort, case-control, and case-crossover designs) involving a total of 506,411 participants that compared patients receiving SSRI therapy with a control group not receiving SSRIs.

In adjusted analyses, the researchers found that people taking an SSRI were about 50% more likely to have ICH than those not taking an SSRI (relative risk [RR], 1.51; 95% confidence interval [CI], 1.26 - 1.81) and about 40% more likely to have intracerebral hemorrhage (RR, 1.42; 95% CI, 1.23 - 1.65).

In a subset of 5 studies, SSRI exposure in combination with oral anticoagulants was associated with an increased risk for 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 (RR, 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).

Absolute Risk Low

But Dr. Hackam said the findings should be viewed with caution. "Because these types of strokes are very rare, the actual increased risk for the average person is very low," he noted in a statement. In absolute risk terms, the researchers estimate 1 additional intracerebral hemorrhage episode per 10,000 persons treated with SSRIs for 1 year.

"Overall, these results should not deter anyone from taking an SSRI when it is needed," Dr. Hackam said.

"In general these drugs are safe, and obviously there are risks to having depression go untreated. But doctors might consider other types of antidepressants for people who already have risk factors for these types of strokes, such as those taking blood thinners, people who have had similar strokes already or those with severe alcohol abuse," he added.

In their editorial, Dr. McGrath and Dr. O'Donnell say the findings "emphasize the importance of appropriate patient selection and avoidance of inappropriate prescribing, which assumes particular importance in patients at increased risk of ICH."

The study authors and editorial writers have disclosed no relevant financial relationships.

Neurology. 2012;79:1844-1845,1862-1865. Editorial Abstract