SSRI Use Resolves Depression, Increases Recurrent Stroke Risk After ICH

Treatment with selective serotonin reuptake inhibitors (SSRIs) following intracerebral hemorrhage (ICH) may relieve depressive symptoms, but also raises the risk for a recurrent ICH,  according to research published in JAMA Neurology.

The study authors analyzed data from people who experienced ICH and were also enrolled in a single-center ICH study at Massachusetts General Hospital. The researchers conducted interviews to learn patients’ pre-stroke history of mood disorders, as well as demographic data and medical history. The study team followed up with participants at 3 and 6 months after their stroke and every 6 months thereafter. The current study included 1279 people with primary ICH, 77 of whom were lost to follow-up.

Median follow-up time to recurrent stroke was 53.2 months (interquartile range [IQR],

42.3-61.2 months). During follow-up, the researchers identified 128 patients with recurrent ICH — an annual rate of 4.2% (95% CI, 3.4%-5.5%). During follow-up, 766 participants (60%) were diagnosed with depression. Of these, 282 (22%) were diagnosed at 3 months after stroke. The remaining 484 (39%) were diagnosed at 6 months or beyond.

Of all the patients, 135 were taking SSRIs at the time of their stroke. Most (111) continued SSRI use after their stroke. An additional 170 patients started taking SSRIs after stroke.

Investigators found an association with SSRI use and depression remission, as well as increased risk of recurrent ICH (subhazard ratio, 1.53 and 1.31, respectively). Other risk factors included non-White race, lower educational attainment, prior history of ICH, lobar ICH location, and the APOE ε2 / ε4 alleles. “It is worth mentioning we did demonstrate larger effect sizes for higher SSRI doses, supporting our hypothesis of a direct biologic association between their use and recurrent ICH,” the study authors wrote.

Several study limitations were noted. SSRI use was based on decisions of the individuals’ healthcare providers, which introduces the possibility of inherent bias. The study authors did not have information on medication compliance.

“Future studies will be required to confirm that clinical, neuroimaging, and genetic markers of ICH recurrence risk can assist in selecting patients most likely to receive net benefit from SSRI treatment of depression after primary ICH,” the authors concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Kubiszewski P, Sugita L, Kourkoulis C, et al. Association of selective serotonin reuptake inhibitor use after intracerebral hemorrhage with hemorrhage recurrence and depression severity [published online August 31, 2020]. JAMA Neurol. doi: 10.1001/jamaneurol.2020.3142