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

• DOI: 10.1016/j.biopsych.2016.03.2108
• Publication Date: 2016-04-11T06:02:33Z
• Authors: Murray A. Raskind; Steven P. Millard; Eric C. Petrie; Kris Peterson; Tammy Williams; David J. Hoff; Kimberly Hart; Hollie Holmes; Jeffrey Hill; Colin Daniels; Rebecca Hendrickson; Elaine R. Peskind
• Keywords: Adult; Male; Combat Disorders; Blood Pressure; Prazosin; Middle Aged; 16. Peace & justice; 3. Good health; Stress Disorders, Post-Traumatic; Young Adult; 03 medical and health sciences; Military Personnel; 0302 clinical medicine; Outcome Assessment, Health Care; Adrenergic alpha-1 Receptor Antagonists; Humans; Female; Biomarkers

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.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.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.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.