Depression is common after stroke, with SSRIs "generally considered first-line treatment agents," Dr. Alessandro Biffi of Massachusetts General Hospital, in Boston, and colleagues note in JAMA Neurology. However, they add, likely due to their anticlotting effects, SSRIs have been linked to an increased risk of first-time ICH.
"We need more information on the use of medications like SSRIs for patients that have had intracranial hemorrhage, because at least on the basis of our study, there is some evidence that it increases the risk of a recurrent brain hemorrhage, even though it does positively affect the severity of depressive symptoms," Dr. Biffi told Reuters Health by phone.
His team looked at 1,279 patients with ICH treated at Mass General between 2006 and 2017. During a median follow-up of 53.2 months, 766 (60%) developed depression and 128 (4.2%) had recurrent ICH. Among patients diagnosed with depression, 55% had resolution of depression during a median follow-up of 26.3 months.
At the time ICH occurred, 135 patients had already been taking SSRIs, and 111 continued to take them. Another 170 patients began taking SSRIs after ICH.
Univariate analysis found that SSRI use, non-white race or ethnicity, less education, previous ICH and lobar ICH were each associated with a greater likelihood of ICH recurrence, as were the APOE e2/e4 alleles. SSRIs were independently associated with repeat ICH, while they were associated with depression remission on both univariate and multivariate analyses.
Patients exposed to SSRIs had 31% higher risk for repeat ICH compared with those who weren't on SSRIs (subhazard ratio, 1.31; 95% confidence interval, 1.08 to 1.59), while their chance of getting over their depression was 53% better (SHR, 1.53; 95% CI, 1.12 to 2.09).
Higher SSRI doses were associated with increased ICH recurrence, but they did not increase the likelihood of depression remission.
For high-risk patients on SSRIs, the risk of ICH recurrence was 6.1% per year, versus 3.8% annually without SSRI exposure. Recurrence rates in the low-risk group were 2.9% with SSRIs and 2.3% without SSRIs.
"Our findings suggest that SSRIs in particular should be considered with caution in these patients with cerebral hemorrhage," Dr. Biffi said. The drugs are especially contraindicated in those who have already had repeated ICH, he added.
"That should be considered a pretty strong contraindication to the use of SSRIs," the researcher said. "It's a very-high-risk population for recurrent brain bleeding in a way that ischemic stroke survivors are not."
The goal, he added, will be to establish biomarkers for recurrent ICH risk that will allow clinicians to weigh the benefit of using SSRIs against the danger of repeat bleeding in an individual patient, "to create a precision-medicine approach."
Dr. Gillian Mead, chair of stroke and elderly-care medicine at the University of Edinburgh, told Reuters Health by email, "Although SSRI use appeared to be associated with a small increase in the risk of recurrent ICH, the observational nature of this research means that we cannot be confident that SSRIs cause recurrent ICH."
"In the largest randomised trial of SSRI for stroke recovery to date (FOCUS, Lancet 2018), which included 309 people with ICH, SSRIs had no effect on the modified Rankin score at 6 months," said Dr. Mead, who was not involved in the study.
Post-stroke depression is typically treated with talking therapies and/or antidepressants, often SSRIs, she noted. "Also, advice should be given to increase physical exercise, as this is likely to reduce disability after stroke and may also improve mood."
Dr. Mead concluded: "Depression is very common after ICH - and occurs in more than half of ICH patients within the first five years of stroke. Physicians should be vigilant and ensure that depression is identified and addressed."
By Anne Harding
SOURCE: https://bit.ly/32KSkYT JAMA Neurology, online August 31, 2020.
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