Antidepressant Use in Veterans with PTSD Tied to Increased Stroke Risk

Allison Gaffey, PhD

In what investigators are calling the largest study of its kind ever conducted, new research is shedding light on potential associations between posttraumatic stress disorder (PTSD) and antidepressant use with an increased risk of hemorrhagic stroke in Veterans.

A 13-year study with data from more than one million Veterans, results suggest patients with PTSD using selective serotonin or norepinephrine reuptake inhibitors (SSRI and SNRI) were at an increased risk of hemorrhagic stroke, but investigators noted only use of SSRIs was independently associated with increased risk after adjustment for confounding factors.

“SSRIs are commonly prescribed to Veterans and to manage the mental health sequelae of trauma in non-VA settings. Further research is needed to understand the cerebrovascular consequences of SSRI use in younger adults treated for PTSD and other psychiatric conditions,” wrote study investigators.

With Veterans Affairs (VA) reporting a prevalence rate of 30% in men and 26.9% in women, PTSD represents one of the largest health crises among Veterans and antidepressants are often prescribed as a treatment for these patients. While SSRIs and SNRIs have a known association with increased risk of bleeding, a team from the VA Connecticut Healthcare System sought to assess how use of antidepressants for treatment of PTSD in young veterans might impact hemorrhagic stroke risk.

With this in mind, a team led by Allison Gaffey, PhD, designed the current study to assess whether use of SSRIs and SNRIs in middle-aged Veterans with PTSD was associated with increased stroke risk and, if there was an association, determining the main driver of this effect. Using data from the VA health system, investigators identified 1,063,973 Veterans who served in support of Operations Enduring Freedom, Iraqi Freedom, or New Dawn.

For inclusion in the current study, participants needed to have at least 1 in patient or 2 outpatient visits at a VA facility from October 1, 2001-November 1, 2014 and have no history of ischemic or hemorrhagic stroke, or transient ischemic attack at first VA visit. After application of this criteria, investigators identified a final sample of 998,090 patients. The final sample had a mean age of 30.18 (SD, 9.19) years, 88% were men, 64% were White, 26% were obese and 57% were current or former smokers. Of the 998,090 included in the study, 28% had PTSD, 37% were prescribed an SSRI, and 7% were prescribed an SNRI.

During the follow-up period, which lasted a mean of 2.14 (SD, 2.67) years, 507 patients suffered a hemorrhagic stroke. The overall stroke incidence was 1.70 per 10,000 person-years. Results indicated absolute incidence rates of 1.83, 2.97, and 2.18 per 10,000 person-years for PTSD, SSRI use, and SNRI use, respectively. In an unadjusted model, PTSD was associated with a significantly greater risk of hemorrhagic stroke (HR, 1.82; 95% CI, 1.48-2.24; P=.03). This analysis also indicated SSRI use and SNRI use were associated with a greater risk of hemorrhagic stroke.

In fully adjusted models, the relationships of PTSD (aHR, 1.03; 95% CI, 0.81-1.34) and SNRI use (aHR, 1.19; 95% CI, 0.83-1.71) with increased hemorrhagic stroke risk were attenuated. However, investigators pointed out SSRI use was still associated with a 45% greater risk of hemorrhagic stroke (aHR, 1.45; 95% CI, 1.13-1.85). Other factors associated with increased stroke in adjusted models included hypertension, drug abuse and alcohol abuse, but non-obesity and being non-Hispanic were considered protective factors.

“Additional granular studies are required to examine effects of medication subtypes and hemorrhagic stroke risk among younger adults to inform clinical recommendations. Providers should review the risk of hemorrhagic stroke with patients when prescribing SSRIs,” added investigators.

This study, “Posttraumatic Stress Disorder, Antidepressant Use, and Hemorrhagic Stroke in Young Men and Women,” was published in Stroke.