This randomized, double-blind, placebo-controlled trial of doxazosin will assess doxazosin's effectiveness for PTSD nightmares, subjective sleep quality, and non-nightmare PTSD symptoms in adult men and women veterans with full and partial-syndromal PTSD.

This study will involve a randomized, double-blind, placebo-controlled, flexible dose trial of doxazosin (1-10mg) for PTSD nightmares, sleep disturbance and overall PTSD symptoms. The target sample will consist of 60 male and female subjects with chronic PTSD symptoms and prominent nightmares randomly assigned to receive doxazosin (n=30) or placebo (n=30). Participants will be enrolled at the San Francisco VA Medical Center. Following baseline consent procedures, eligibility assessments, and 1-week of baseline assessments including self-report surveys, actigraphy, and at-home EEG (Sleep Profiler), all subjects will initiate doxazosin or equivalently marked placebo at 1mg at bedtime. Subjects will undergo a 4-week titration phase during which doxazosin or placebo may be increased to a maximum dose of 10mg (or equivalently marked placebo) at bedtime based on symptoms and tolerability. After the 4-week titration phase, subjects will continue at stable dose of study medication for a 4-week stable dose phase. Subjects will be asked to complete sleep diaries daily during their participation in the study. In the last week of the stable dose phase, participants will undergo an additional week of at-home sleep monitoring using actigraphy, complete end of treatment surveys, and undergo end-of-treatment clinical assessments and discontinuation of study medication. After discontinuation of study medication, participants will complete three additional days of sleep diaries.

Inclusion Criteria:

• U.S. military veteran or civilian;
• age 18-75 and
• current full syndromal PTS as indexed by the CAPS-5 (Clinician-administered PTSD scale) or have a current CAPS-5 score ≥ 20, and CAPS-IV recurrent distressing dreams item of ≥ 3; or a CAPS-5 score ≥ 12, and CAPS-IV recurrent distressing dream item of ≥ 4.

Exclusion Criteria:

• DSM-5 current moderate to severe alcohol or drug use disorder in the last 3 months; moderate alcohol or drug use disorder in the last 3 months will be reviewed on a case-by-case basis;
• history of any psychiatric disorder with active psychosis or mania in the past 5 years;
• exposure to trauma within the last 3 months;
• prominent suicidal or homicidal ideation;
• score of 16 or greater AHI based on ApneaLink data analysis in the absence of effective sleep treatment (such as CPAP or oral device)
• neurologic disorder or systemic illness affecting central nervous system function;
• chronic or unstable medical illness including unstable angina, myocardial infarction within the past 6 months, congestive heart failure, preexisting hypotension or standing systolic blood pressure < 100 mmHg at eligibility (V0); orthostatic hypotension defined as orthostatic systolic decrease after 3 minutes standing >20 mmHg or any BP decrease accompanied by lightheadedness; complete heart block or arrhythmia on ECG; chronic renal or hepatic failure, and pancreatitis;
• history of priapism or refusal to hold off on as needed phosphodiesterase inhibitors;
• pregnancy, breastfeeding and/or refusal to use effective birth control (female participants);
• previous adverse reaction to an alpha-1-antagonist;
• current use of a medication with alpha-1 blocking properties for insomnia, alpha-1 antagonists, alpha-2 agonists, boceprevir; midodrine; and
• use of yohimbine, Ma huang or other non-FDA approved substances or herbal remedies that the investigators consider pose a risk to participation
• homelessness (includes living in a temporary shelter);
• subjects who, in the opinion of the investigator, are otherwise unsuitable for a study of this type.

Participants taking SSRIs, duloxetine, bupropion, mirtazapine, and venlafaxine may be included if they have been on a stable dose for 4 weeks. Participants may be included if they are in psychotherapy treatment as long as they do not participate in evidence-based trauma-focused or nightmare-focused psychotherapy (such as cognitive processing therapy, prolonged exposure therapy, or imagery rehearsal therapy) while in the trial. Participants who are normotensive and do not have orthostatic hypotension while on stable-dose beta-blocker may be included in the study.