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

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• 作者：Murray A. Raskind^a ; ^b ; ^{murray.raskind@va.gov" class="auth_mail" title="E-mail the corresponding author} ; Steven P. Millard^a ; Eric C. Petrie^a ; Kris Peterson^c ; Tammy Williams^c ; David J. Hoff^a ; Kimberly Hart^a ; Hollie Holmes^a ; ^b ; Jeffrey Hill^c ; Colin Daniels^c ; Rebecca Hendrickson^a ; Elaine R. Peskind^a ; ^b
• 关键词：Biomarker ; Blood pressure ; Military ; Noradrenergic ; Posttraumatic stress disorder (PTSD) ; Prazosin ; Treatment response
• 刊名：Biological Psychiatry
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：80
• 期：10
• 页码：736-742
• 全文大小：543 K

文摘

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.