Prazosin for Post-Concussive Headaches

Background and Rationale: Headaches following mild traumatic brain injury (mTBI) are common, can be refractory to standard therapies, and may persist and worsen to become a debilitating chronic pain syndrome. The purpose of this study is to evaluate the centrally acting alpha-1 adrenoreceptor (AR) antagonist drug prazosin as a prophylactic treatment for chronic posttraumatic headaches (PTHAs). The impetus for this study comes from a large open-label case series in Iraq and Afghanistan Veterans with mTBI and PTHAs and data from a placebo-controlled trial evaluating use of prazosin for posttraumatic stress disorder (PTSD) in active-duty Servicemembers (SMs). Findings from these studies showed that in addition to decreasing PTSD-related symptoms and improving sleep quality, prazosin decreased the frequency and severity of headaches, which were common in the study populations. Study Objectives, Specific Aims, and Hypotheses: The objective of this study is to evaluate the efficacy of prazosin as a prophylactic treatment for persistent PTHAs, which will be accomplished by conducting a randomized placebo-controlled double blind trial of prazosin vs. placebo in active-duty SMs and Veterans who were in military service at any time from October 7, 2001 to the present with persistent PTHAs. * Specific Aim 1: To determine the effect of prazosin compared to placebo on headache frequency, headache severity and duration, use of abortive/analgesic medications, and headache-related disability. * Specific Aim 2: To determine the effect of prazosin on sleep disturbance, PTSD symptoms, depressive symptoms, alcohol consumption, global cognitive function, health-related quality of life, and global clinical status.