SSRIs May Worsen Hemorrhagic Strokes

Danish researchers suggest that for some patients, taking selective serotonin reuptake inhibitors (SSRIs) leading up to a stroke may worsen the event. 

Among patients with hemorrhagic strokes, use of an SSRI in the 90 days before symptom onset was associated with a greater likelihood of stroke severity and mortality within 30 days, according to the new study in the journal Stroke.
____________________________________________________________________________________________________________________________________________________________________

RELATED CONTENT
Major Depression: Treatment in Primary Care
Psychotropic-Induced Weight Gain: A Review of Management
____________________________________________________________________________________________________________________________________________________________________

Although pre-stroke depression in itself may increase stroke severity and mortality, this wasn’t the case in SSRI users with ischemic stroke.

“The difference between the ischemic and hemorrhagic stroke group is very interesting,” says Janne Mortensen, MD, of Aarhus University Hospital in Denmark. “SSRI treatment may increase the risk of the hemorrhagic strokes being severe, whereas a possible neuroprotective effect in ischemic stroke may also be present.”

Mortensen and colleagues looked at pre-stroke SSRI use and stroke outcomes using national registry data on adults who had a first-ever hemorrhagic or ischemic stroke in Denmark from January 2003 to November 2012.

Their analysis included 626 SSRI users with a hemorrhagic stroke and 4,478 with an ischemic stroke, as well as an equal number of propensity score-matched controls who had not filled an SSRI prescription in the previous 90 days.

Of the patients with hemorrhagic strokes, 45.8% had a severe event and 36.8% died within 30 days, compared to 18.7% and 10.7% in patients with ischemic stroke.

“It is possible that SSRI treatment in the hemorrhagic stroke patients—through its anti-platelet effects—mediates hematoma growth, which leads to more severe symptoms and an increased risk of death within 30 days,” Mortensen says.

However, because the patients in this study were not randomized to treatment or placebo, he says the phenomenon of “confounding by indication” should be kept in mind. “Thus, the SSRI-treated patients in this study are most likely treated for a depression which, in itself, could increase the risk of morbidity and mortality,” he says. “This may be part of the explanation for the observed association between SSRI treatment and increased risk of the hemorrhagic strokes being severe.”

So why didn’t they see the same association between SSRI treatment and stroke severity and mortality in ischemic stroke? “The possible neuroprotective effect of SSRIs in ischemic stroke may be at least part of the explanation,” Mortensen says.

He and his colleagues have said further studies in this area are warranted. They are currently conducting several clinical studies to identify stroke patient subsets more susceptible to the effects of SSRI treatment—the anti-depressive effect, the possible anti-thrombotic effect, and the possible neuroprotective effect.

For now, Mortensen says there is no reason, based on their results, to refrain from prescribing an SSRI when treatment is otherwise indicated.

“Our results do not show an increased risk of hemorrhagic stroke in SSRI-treated patients; what we find is an association between SSRI treatment and an increased risk of the hemorrhagic strokes being severe,” he says. “It is being discussed whether SSRI treatment should be prescribed more or less routinely after stroke (given the possible neuroprotective effects) and our results at least warrant caution, if considering this approach in hemorrhagic stroke patients.”

—Colleen Mullarkey

Reference

Mortensen JK, Larsson H, Johnsen SP, Andersen G. Impact of pre-stroke selective serotonin reuptake inhibitor treatment on stroke severity and mortality. Stroke. June 3, 2014. [Epub ahead of print].