In a recent publication in the journal Stroke, results from a 13-year study that is considered to be the largest study of its kind involving more than 900,000 Veterans with posttraumatic stress disorder (PTSD), suggest that the use of selective serotonin or norepinephrine reuptake inhibitors was linked to an expanded risk of hemorrhagic stroke. The results of this study shed light on the possible associations between PTSD and antidepressant use and a heightened risk of hemorrhagic stroke in veterans.

Gaffey et al assessed the independent effects of PTSD and selective serotonin and norepinephrine reuptake inhibitors (SSRIs and SNRIs) on the risk of incident hemorrhagic stroke in a nationwide sample of 1.1 million young and middle-aged veterans. Time-varying multivariate Cox models were utilized to investigate hemorrhagic stroke risk by PTSD status and use of SSRIs or SNRIs while adjusting for demographics, lifestyle factors, stroke, and psychiatric comorbidities. During 13 years of follow-up (2.14 years on average), 507 patients (12% women) suffered a hemorrhagic stroke. The overall prevalence rate was 1.70 events per 10,000-person years.

In unadjusted models, PTSD was linked to an 82% greater risk of new-onset hemorrhagic stroke (hazard ratio [HR], 1.82 [95% CI, 1.48-2.24]), SSRI use was linked with a >2-fold risk (HR, 2.02 [95% CI, 1.66-2.57]), and SNRI use was correlated with a 52% greater risk (HR, 1.52 [95% CI, 1.08-2.16]). The study results also revealed that in fully adjusted models, effects of PTSD and SNRI use were diminished (adjusted HR, 1.03 [95% CI, 0.81-1.34]; adjusted HR, 1.19 [95% CI, 0.83-1.71]), but SSRI use remained associated with a 45% greater risk of hemorrhagic stroke (adjusted HR, 1.45 [95% CI, 1.13-1.85]).

Hypertension, drug abuse, and alcohol abuse were also associated with augmented stroke risk. Researchers indicated that nonobesity and being non-Hispanic were protective factors and in sensitivity investigations, healthcare utilization was a small but considerable predictor of stroke. The researchers concluded that in the largest known examination of PTSD and antidepressant-associated risk for hemorrhagic stroke in young adults, SSRI use, but not PTSD use or SNRI use, was independently linked to incident stroke.

The researchers also noted that SNRIs may be preferable for treating PTSD and comorbid conditions, although pursuing other modifiable risk factors and nonpharmacologic treatments for PTSD also remains critical.

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