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 \[systolic blood pressure\<110\] or orthostatic hypotension \[systolic drop \>20 mm Hg after 2 min standing accompanied by lightheadedness\], 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 studies * Women of childbearing potential must not be pregnant, planning to become pregnant during the study period, or nursing. * Participation in a HA support group or other activity such as meditation or yoga intended to mitigate HA or other chronic pain must be stable at least 4 weeks prior to beginning the initial screen (P1) visit and may not be started during the study * Failure to record HA data for at least 80% of days during the Screening Period * Not suitable for study per clinician judgement. Medication-and other Treatment-Related Considerations: * The use of HA rescue or symptom-relieving medications will be allowed during the study. This includes triptans, ergotamines, opioids, simple analgesics (e.g. acetaminophen, aspirin, or non-steroidal anti-inflammatories \[NSAIDS\], and combination analgesics. Their use will be recorded on the concurrent medication case report form (CRF) during the Preliminary Screening Period (P1) and throughout the remainder of the study. Randomization of participants will be stratified based on whether their use of HA medications meets International Classification of Headache Disorders 3rd addition (ICHD-3 beta) criteria for overuse of these medications, as described in section 5.5 below. * Opioid Medications: Use of opioids for treatment of HA or non-HA-related pain or for any other purpose is allowed during the study. Any opioid use would ideally be excluded due to potential confounding effects on interpretation of response to treatment. However, in this population, particularly in Veterans with chronic pain or undergoing minor orthopedic or dental procedures, opioid use is common. Use of opioids, including frequency and dose, will be recorded on the concurrent medication CRF. * Cannabis: The use of cannabis in any form is not excluded unless its use meets criteria for Cannabis Use Disorder. All use of cannabis will be documented. * Other Medications: Participants who are using other medications or treatments on a routine basis must be on a stable dose for at least 4 weeks prior to the Preliminary Screening Period (P1), and must intend to continue the medication at the same regimen for the duration of the trial unless lack of efficacy, safety, or tolerability dictates otherwise. The following medications and treatments are not excluded: * Psychoactive drugs (for example, anticonvulsants, benzodiazepines, antidepressants, sedative/hypnotics), * Antihypertensive medications (including beta-blockers, calcium channel blockers, angiotensin converting enzyme \[ACE\] inhibitors, and angiotensin receptor blockers), * The use of magnesium in any dose that is prescribed for the purpose of HA prevention or treatment. The incidental use of magnesium in multi-vitamins, laxatives, etc. is permissible but must be documented. * Hormones (for example, testosterone, estrogen, or progesterone) in any form. * Onabotulinum toxin A and nerve block injections for the purpose of HA prevention are permissible if the treatment response has been stable during the two most recent treatment cycles. * The "as-needed" (prn) use of any non-exclusionary medications is allowed; however, such use must be discussed with a clinician prescriber and documented. * The use of butalbital in any form within 4 weeks of beginning the Preliminary Screening Period (P1) through the end of the participant's study involvement is exclusionary. * Participants who have been taking trazodone will undergo a 2-week washout period before the Preliminary Screening Period (P1 visit). Combining prazosin and trazodone may increase the risk of priapism. We have decided to begin the washout period before the Preliminary Screening Period in order to remove any confounding variables while on the headache log and actigraphy. * Sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra) will not be permitted during the study drug dose Titration Period, because of increased risk of hypotension in combination with alpha-1 blockers, but will be allowed at half the usual starting dose following the study drug dose Titration Period, per VA prescribing guidelines. * Use of supplements containing nitrates and supplements containing stimulants (such as ephedra) are exclusionary in the two weeks prior to initial screen (P1) visit and prohibited throughout the study. Participants who take these supplements will be asked to discontinue them for a minimum of two weeks before the Preliminary Screening Period (P1 visit). * Use of prescribed stimulants (such as amphetamine or dextroamphetamine containing medications) is exclusionary in the 2 weeks prior to the initial screen (P1) visit and prohibited throughout the study. Participants who take these medications will be asked to discontinue them for a minimum of 2 weeks before the Preliminary Screening Period.