期刊
BIOLOGICAL PSYCHIATRY
卷 80, 期 10, 页码 736-742出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2016.03.2108
关键词
Biomarker; Blood pressure; Military; Noradrenergic; Posttraumatic stress disorder (PTSD); Prazosin; Treatment response
资金
- Department of Veterans Affairs
- US Army Medical Research and Materiel Command, Fort Detrick, MD
- Pfizer
- Merck
- Takeda Pharmaceuticals
- Eli Lilly and Company
- INSYS Therapeutics
- Avanir Pharmaceuticals
BACKGROUND: In a previously reported positive randomized controlled trial of the alpha(1)-adrenoreceptor (alpha(1)AR) antagonist prazosin for combat posttraumatic stress disorder (PTSD) in 67 active duty soldiers, baseline symptoms did not predict therapeutic response. If increased brain alpha(1)AR activation in PTSD is the target of prazosin treatment action, higher brain alpha(1)AR activation should predict greater prazosin efficacy. Although brain alpha(1)AR activation is not measurable, coregulated peripheral alpha(1)AR activation could provide an estimate of brain alpha(1)AR activation. Standing blood pressure (BP) is an accessible biological parameter regulated by norepinephrine activation of alpha(1)ARs 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 alpha(1)AR activation contributing to PTSD pathophysiology in a subgroup of patients.
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