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Use of the selective serotonin reuptake inhibitors (SSRI) class of antidepressants conferred a small, but statistically significant danger of brain hemorrhage, according to an investigation of multiple epidemiologic studies.

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

Another evaluation showed that concomitant use of an anticoagulant and an SSRI significantly increased the danger of brain hemorrhage compared with anticoagulant use alone.

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

“SSRI exposure is associated with a greater risk of intracerebral and intracranial hemorrhage, yet given the rarity of the event, absolute dangers are likely to be rather low,” they wrote in conclusion.

“While the data we reviewed were not randomized, we believe clinicians might consider alternative categories of antidepressants in patients with intrinsic risk factors for intracerebral hemorrhage, for example those receiving long term oral anticoagulation, people with previous intracranial bleeding, and patients with cerebral amyloid angiopathy or serious alcohol abuse,” they added.

SSRIs are the most widely used group of antidepressant drugs. As a class, the drugs inhibit platelet aggregation, introducing a known risk of gastrointestinal bleeding, the authors noted in their launch. Since the few studies examining the problem generated conflicting results whether SSRI use increases the danger of brain hemorrhage has remained unclear.

In a effort to bring some clarity to the contradictory data, Mrkobrada and Hackam performed a systematic review and meta-analysis of studies assessing the association between SSRI use and brain hemorrhage, pooling studies based on the kind of hemorrhage reported.

A literature search retrieved 2,493 citations, which the writers culled to 16 pertinent studies including a cumulative total of 506,411 patients. Four of the studies had a case control design, as well as the rest were cohort investigations. All but three of the studies contained multivariate and univariate risk estimates.

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

Statistically significant effects were given by only two classes. 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.

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In a subset of five studies (three looking at intracranial hemorrhage and one each reporting hemorrhagic stroke and intracerebral hemorrhage), SSRI exposure together with oral anticoagulants was linked with a greater 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 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 firmly related to hemorrhagic events than was longterm use.

The authors noted 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 in the pool of patients in danger for hemorrhage.”

The meta-analysis represents the “best present evidence of an association between SSRI use and also the chance of [brain hemorrhage],” the authors of an accompanying editorial composed of the findings. Nonetheless, they seconded the careful decisions of Mrkobrada and Hackam.

“A key concern is the absolute risk increase related to SSRIs is quite little for the average patient,” wrote Emer R. McGrath, MB, and Martin J. O’Donnell, MB, PhD, of the National University of Ireland in Galway. “Therefore, for patients with an obvious indication for SSRI use, the absolute increase in risk of [brain hemorrhage] shouldn’t deter clinicians from prescribing these agents.”

“Nonetheless, these findings emphasize the need for appropriate patient choice and avoidance of inappropriate prescribing.”

Source: Antidepressants Linked to Risk of Stroke

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