Prazosin for Post-Concussive Headaches

Inclusion Criteria

• Male and female Active-duty Servicemembers (SMs) or Veterans aged 18 or older who are in good general health.
• History of blast and/or impact head trauma mild traumatic brain injury (mTBI) meeting Defense and Veterans Brain Injury Center (DVBIC) mTBI criteria.

o Mild TBI is defined as an injury to the head causing at least one of the following: alteration in consciousness (for up to 24 hours after the injury), loss of consciousness (0-30 minutes), and/or post-traumatic amnesia (up to 1 day post-injury). If available, the Glasgow Coma Scale score must be 13-15, and head imaging findings (if imaging was performed) must be negative.

• Frequent headaches (HAs) that started within 3 months after a head injury or marked worsening (a two-fold or greater increase in frequency and/or severity) of pre-existing headaches within 3 months of head injury.
• HAs either 1) must last 4 or more hours a day and reach a moderate to severe intensity at any point during the headache, or 2) may be of any severity or duration if the participant takes a medication or other agent in an effort to stop or treat a headache.
• HAs meeting these criteria must have been present on average at least 8 days per 4-week period and occurring at a stable level by self-report for at least 3 months prior to the Initial Screening Visit. The 4-week HA frequency/severity criteria must be confirmed during the Preliminary Screening Period.
• Participants of childbearing potential must agree to abstain from sexual relations that could result in pregnancy or use an effective method of birth control acceptable to both participant and the clinician prescriber during the study. Participants who are not of childbearing potential are not required to use contraception during the study.
• Participants must have English fluency sufficient to complete study measures.

Exclusion Criteria

• Participation in other interventional research.
• History of penetrating head injury
• History of TBI more severe than mild by DVBIC criteria
• A primary non migraine and/or tension-type HA disorder (for example hemicrania continua; cluster) that accounts for the majority of current symptoms.
• HAs of any kind of moderate or severe intensity on an average of more than 4 days per month preceding the concussive trauma
• Acute or serious medical illness or unstable chronic medical illness (e.g., unstable angina, myocardial infarction within 6 months, congestive heart failure, clinically significant or concerning cardiac arrhythmias; preexisting hypotension [systolic blood pressure 20 mm Hg after 2 min standing accompanied by lightheadedness], chronic renal or hepatic failure, or acute pancreatitis. The eligibility of potential participants having acute serious and/or chronic medical illnesses other than those listed will be evaluated on a case-by-case basis by a study physician, physician assistant - certified (PA-C), or advanced registered nurse practitioner (ARNP).
• Use of prazosin or other alpha-1 antagonist (including but not limited to alfuzosin, doxazosin, silodosin, tamsulosin, terazosin) for any purpose in the 2 weeks prior to initial screen (P1) visit and prohibited throughout the study
• Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist
• Active psychosis or psychotic disorder, severe depression (as determined per clinician prescriber judgment), severe psychiatric instability or severe situational life crisis (including evidence of being actively suicidal or homicidal).
• Meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for any Substance Use Disorder except caffeine-related disorders, or tobacco-related disorders.
• History of delirium within the prior 3 months, epilepsy, stroke, dementia, psychotic disorder, or bipolar disorder
• Structural brain abnormalities on any prior imaging with associated clinically evident manifestations
• Current participation in transcranial magnetic stimulation studi