Higher Pretreatment Blood Pressure Is Associated With Greater Posttraumatic Stress Disorder Symptom Reduction in Soldiers Treated With Prazosin.
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.
Northwest Network Veterans Integrated Service Network 20 Mental Illness Research, Education and Clinical Center; Seattle; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle. Electronic address: murray.raskind@va.gov.
Murray A
MA
Raskind
Northwest Network Veterans Integrated Service Network 20 Mental Illness Research, Education and Clinical Center; Seattle.
Steven P
SP
Millard
Northwest Network Veterans Integrated Service Network 20 Mental Illness Research, Education and Clinical Center; Seattle.
Eric C
EC
Petrie
Madigan Army Medical Center, Tacoma, Washington.
Kris
K
Peterson
Madigan Army Medical Center, Tacoma, Washington.
Tammy
T
Williams
Northwest Network Veterans Integrated Service Network 20 Mental Illness Research, Education and Clinical Center; Seattle.
David J
DJ
Hoff
Northwest Network Veterans Integrated Service Network 20 Mental Illness Research, Education and Clinical Center; Seattle.
Kimberly
K
Hart
Northwest Network Veterans Integrated Service Network 20 Mental Illness Research, Education and Clinical Center; Seattle; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle.
Hollie
H
Holmes
Madigan Army Medical Center, Tacoma, Washington.
Jeffrey
J
Hill
Madigan Army Medical Center, Tacoma, Washington.
Colin
C
Daniels
Northwest Network Veterans Integrated Service Network 20 Mental Illness Research, Education and Clinical Center; Seattle.
Rebecca
R
Hendrickson
Northwest Network Veterans Integrated Service Network 20 Mental Illness Research, Education and Clinical Center; Seattle; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle.
Elaine R
ER
Peskind
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects*; D003130:Combat Disorders / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008889:Military Personnel; D017063:Outcome Assessment, Health Care; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy*; D055815:Young Adult
D058668:Adrenergic alpha-1 Receptor Antagonists; D015415:Biomarkers; D011224:Prazosin
Biomarker; Blood pressure; Military; Noradrenergic; Posttraumatic stress disorder (PTSD); Prazosin; Treatment response