Brain Receptor Function in Post-Traumatic Stress Disorder

INCLUSION CRITERIA: 18 to 65 years of age. Male and female. Score greater than or equal to 50 on the Clinician-Administered PTSD Scale (CAPS-2) as a baseline measure of PTSD symptom severity. Capable of providing informed consent, obtained prior to any study procedures. Free of all psychotropic medication for at least 2 weeks, excluding short-term hypnotics. Patients who were treated with fluoxetine will only be included after a medication free period of at least 8 weeks. Good physical health, confirmed by a complete physical exam (including normal vital signs), electrocardiogram, neurologic exam, and routine laboratory tests of blood and urine. However, if patients have participated in other research studies or have had blood work through their primary MD within the last 6 months, these results will be used instead of repeating blood draws for inclusion into the study. EXCLUSION CRITERIA: Patients who meet DSM-IV criteria for substance abuse (alcohol or drugs) or substance dependence within 6 months prior to screening. The effect of abuse/dependence on phenomenology and biology could mask and exceed PTSD effect. Patients at current risk for homicide or suicide. All additional DSM IV Axis I comorbidity, excluding secondary diagnoses of major depressive disorder (MDD) or anxiety disorder (AD). Given the high comorbidity of these disorders in PTSD, and since excluding such patients would not provide the full spectrum of the disorder, only patients in whom axis I diagnoses of MDD and AD preceded onset of PTSD will be excluded. Pregnant women (all stages) and women of childbearing potential who are not practicing a clinically accepted method of contraception or who have a positive pregnancy test or who are lactating. Blood donation (1 Red Cross Unit) within the 8 weeks preceding the study. This is the minimal safe period between consecutive donations. Subjects who are doing well on medication. Although we will only recruit non-medicated patients, the decision to stop medication will be taken purely on clinical grounds. No subject will be taken off medication solely to participate in the study. Unable to comply with study procedures or assessments as regards the screening evaluation (i.e. PTSD diagnosis, health requirements, etc.) and the 3 hospitalization for evaluation of glucocorticoid and mineralocorticoid receptor function. Subjects who are allergic to mifepristone, paroxetine or spironolactone, and subjects with any contraindication to treatment with these agents (as described in their current labeling), will be excluded from participation in the study.