Higher Pretreatment Blood Pressure Is Associated With Greater Posttraumatic Stress Disorder Symptom Reduction in Soldiers Treated With Prazosin

Abstract

Background: In a previously reported positive randomized controlled trial of the α₁-adrenoreceptor (α₁AR) antagonist prazosin for combat posttraumatic stress disorder (PTSD) in 67 active duty soldiers, baseline symptoms did not predict therapeutic response. If increased brain α₁AR activation in PTSD is the target of prazosin treatment action, higher brain α₁AR activation should predict greater prazosin efficacy. Although brain α₁AR activation is not measurable, coregulated peripheral α₁AR activation could provide an estimate of brain α₁AR activation. Standing blood pressure (BP) is an accessible biological parameter regulated by norepinephrine activation of α₁ARs on peripheral arterioles.

Methods: Effects of baseline standing systolic and other BP parameters on PTSD outcome measures from the previously reported randomized controlled trial were analyzed using linear mixed-effects models. Prazosin participants (n = 32) and placebo participants (n = 35) were analyzed separately.

Results: In prazosin participants, each 10-mm Hg higher baseline standing systolic BP increment resulted in an additional 14-point reduction (improvement) of Clinician-Administered PTSD Scale total score at end point (p = .002). All other combinations of baseline BP parameters and PTSD outcome measures were similarly significant or demonstrated trends in the predicted direction. In placebo participants, there was no signal for a baseline BP effect on PTSD outcome measures.

Conclusions: These findings suggest that higher standing BP is a biomarker that helps identify persons with combat PTSD who are likely to benefit from prazosin. These results also are consistent with α₁AR activation contributing to PTSD pathophysiology in a subgroup of patients.

Trial registration: ClinicalTrials.gov NCT00990106.

Keywords: Biomarker; Blood pressure; Military; Noradrenergic; Posttraumatic stress disorder (PTSD); Prazosin; Treatment response.