Science Talk: Antidepressants May Increase Risk of Stroke and Death



Antidepressants Linked to Risk of Stroke

A separate analysis showed that concomitant use of an SSRI and an anticoagulant significantly increased the risk of brain hemorrhage compared with anticoagulant use alone.

By Charles Bankhead, MedPage Today

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WEDNESDAY, October 17, 2012 (MedPage Today) —Use of the selective serotonin reuptake inhibitors (SSRI) class of antidepressants conferred a small, but statistically significant risk of brain hemorrhage, according to an analysis of multiple epidemiologic studies.

SSRI users had a 40 percent to 50 percent increase in the relative risk of intracranial and intracerebral hemorrhage compared with people who had never taken one of the drugs, according to Daniel G. Hackam, MD, PhD, and Marko Mrkobrada, MD, of the University of Western Ontario in Hamilton.

A separate analysis showed that concomitant use of an SSRI and an anticoagulant significantly increased the risk of brain hemorrhage compared with anticoagulant use alone.

Although the analysis yielded statistically significant results, investigators offered a cautious assessment of the implications in an article reported in the Oct. 30 issue of Neurology.

"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," they wrote in conclusion.

"While the data we reviewed were not randomized, we believe clinicians might consider alternate classes of antidepressants in patients with intrinsic risk factors for intracerebral hemorrhage, such as those receiving long-term oral anticoagulation, individuals with previous intracranial bleeding, and patients with cerebral amyloid angiopathy or severe alcohol abuse," they added.

SSRIs are the most widely used class of antidepressant drugs. As a class, the drugs inhibit platelet aggregation, posing a known risk of gastrointestinal bleeding, the authors noted in their introduction. Whether SSRI use increases the risk of brain hemorrhage has remained unclear, since the few studies examining the issue produced conflicting results.

In an effort to bring some clarity to the conflicting data, Hackam and Mrkobrada performed a systematic review and meta-analysis of studies evaluating the association between SSRI use and brain hemorrhage, pooling studies according to the type of hemorrhage reported.

A literature search retrieved 2,493 citations, which the authors culled to 16 relevant studies involving a cumulative total of 506,411 patients. Four of the studies had a case-control design, and the rest were cohort investigations. All but three of the studies included univariate and multivariate risk estimates.

The studies were separated into four categories, according to their outcome of interest: intracranial hemorrhage, hemorrhagic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

Only two categories yielded statistically significant results. SSRI use was associated with adjusted risk ratios of 1.51 for intracranial hemorrhage (95 percent CI 1.26 to 1.81) and 1.42 for intracerebral hemorrhage (95 percent CI 1.23 to 65). Results were similar in fixed-effects and random-effects models.

In a subset of five studies (three looking at intracranial hemorrhage and one 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 percent CI 1.33 to 1.83).

SSRI use was not associated with hemorrhagic stroke or subarachnoid hemorrhage in either an unadjusted or adjusted analysis.

Seven studies included analysis of effect by duration of exposure to SSRI therapy. Six of the seven found that recent, short-term exposure was more strongly associated with hemorrhagic events than was long-term use.

The authors noted that the finding was consistent with the "reported diminution of platelet function following several weeks of exposure to SSRIs. Platelet function may improve with prolonged exposure, or short-term exposure might deplete susceptible patients from the pool of patients at risk for hemorrhage."

The meta-analysis represents the "best current evidence of an association between SSRI use and the risk of [brain hemorrhage]," the authors of an accompanying editorial wrote of the findings. However, they seconded the cautious conclusions of Hackam and Mrkobrada.

"A key consideration is that the absolute risk increase associated with SSRIs is very small for the average patient," wrote Emer R. McGrath, MB, and Martin J. O'Donnell, MB, PhD, of the National University of Ireland in Galway.






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Date: 06.12.2018, 18:09 / Views: 32184