A Pilot Study to Assess the Effects of Doxazosin on Polysomnography in PTSD

This pilot study will assess the effects of doxazosin on objective measures of sleep in PTSD
subjects using home ambulatory polysomnography. Twenty (20) men and women with chronic PTSD
will be enrolled at the San Francisco Veterans Affairs Medical Center. After initial
screening, subjects will complete 1 week of baseline assessments including 2 nights of home
ambulatory polysomnography. They will then participate in a 2-week flexible-dose titration
of doxazosin based on clinical response and adverse effects followed by 6 weeks of steady
dose treatment ending with 2 nights of home polysomnography. Subjective and rater-based
assessments will be conducted at baseline and at set intervals during and at the end of
treatment. Wrist actigraphy measurements will also be made at baseline and at end of
treatment as an economical, fairly valid and unobtrusive measure of sleep duration. We
hypothesize that doxazosin will be associated with an increase in total sleep time (TST) and
a decrease in wake time after sleep onset (WASO). We hypothesize that doxazosin will also be
associated with clinical gains with respect to nightmares, subjective sleep quality,
non-sleep PTSD symptoms, depression symptoms, and quality of life.

Inclusion Criteria:

1. Age 18-69

2. Current full or partial syndromal PTSD of at least 3 months duration as indexed by
the CAPS (Clinician-administered PTSD scale) score >30

3. CAPS recurrent distressing dreams item of >/= 5

Exclusion Criteria:

1. alcohol and or drug abuse/dependence in the last 3 months

2. lifetime history of any psychiatric disorder with psychotic features, bipolar
disorder, obsessive-compulsive disorder

3. exposure to trauma within the last 3 months

4. prominent suicidal or homicidal ideation

5. sleep apnea diagnosis or positive screen for sleep apnea by Type III device.

6. neurologic disorder or systemic illness affecting CNS function

7. history of brain trauma or head injury with loss of consciousness greater than 10
minutes

8. chronic or unstable medical illness including unstable angina, myocardial infarction
within the past 6 months, congestive heart failure, preexisting hypotension or
orthostatic hypotension, chronic renal or hepatic failure, and pancreatitis

9. pregnancy, breastfeeding and/or refusal to use effective birth control

10. previous serious adverse reaction to an alpha-1-antagonist (such as priapism,
hepatitis, angioedema, or intraoperative floppy iris syndrome)

11. current use of trazodone, hypnotics/benzodiazepines, mirtazapine, atypical
antipsychotics, beta-adrenergic blockers, alpha-2-agonists, and current prazosin or
other alpha-1-antagonists

12. previous non-response to prazosin for treatment of PTSD related sleep disturbance

Participants taking SSRIs, bupropion, venlafaxine and duloxetine may be included if they
have been on a stable dose for 2 months. Participants may be included if they have been
stable in psychotherapy treatment for 2 months and/or if they begin no new psychotherapy
while in the trial.