Nurose Karim, MD

Gaffey AE, Rosman L, Burg MM, Haskell SG, Brandt CA, Skanderson M, Dziura J, Sico JJ. Posttraumatic Stress Disorder, Antidepressant Use, and Hemorrhagic Stroke in Young Men and Women: A 13-Year Cohort Study. Stroke. 2021;52:121–129.

Posttraumatic stress disorder (PTSD) is a commonly encountered mental disorder, especially among veterans. It has an association with ischemic stroke among younger adults, but it may also be associated with early-onset hemorrhagic stroke by modulating inflammatory and atherosclerotic pathways.

The authors in this article assessed an independent and combined risk for incident hemorrhagic stroke, which represents up to 50% of incident stroke cases, and the association with PTSD and the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) medication in a nationwide sample of 1.1 million young and middle-aged U.S. veterans who served in support of the Iraq and Afghanistan conflicts.

SSRI/SNRI (e.g., fluoxetine, sertraline, venlafaxine) are widely used as first-line pharmacotherapies for PTSD because of their safety and tolerability. Due to their antiplatelet effects, their use increases the risk of abnormal bleeding, including intracranial hemorrhage.

In multivariable models adjusted for important confounders such as hypertension and drug use, the association of PTSD and SNRI with stroke was no longer statistically significant, providing a potential explanation that is mediated through traditional cardiovascular disease risk factors. The authors have found that there was still an association in adjusted models between SSRI use and subsequent hemorrhagic stroke, though the overall absolute risk was low.

The results from this study cannot be applied to the generalized population due to several reasons. The cohort mentioned in this study are relatively young and have higher incidence of hypertension and substance and tobacco use. Furthermore, there is likely residual confounding from measures of severity of hypertension and other cardiovascular disease risk factors with PTSD and the study medications. The authors did an adjustment of the confounders by adjusting the health care utilization to partly address the limitation using c-statistics. But it only marginally improved the outcome.

Therefore, based on the limitations of the study, the results are not applicable to the generalized population and the use of a pharmacological arm for the treatment of PTSD should not be withheld, if needed, especially considering that PTSD can impact the quality of life in the high-risk population and the associated comorbidities that it carries, such as anxiety and depression, among others. However, one should be vigilant and mindful in managing risk factors for hemorrhagic stroke, especially in the high-risk younger population.