%0 Journal Article
%T A Pilot Study of Mifepristone in Combat-Related PTSD
%A Julia A. Golier
%A Kimberly Caramanica
%A Rebecca DeMaria
%A Rachel Yehuda
%J Depression Research and Treatment
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/393251
%X Background. We obtained pilot data to examine the clinical and neuroendocrine effects of short-term mifepristone treatment in male veterans with PTSD. Methods. Eight male veterans with military-related PTSD completed a randomized, double-blind trial of one week of treatment with mifepristone (600£¿mg/day) or placebo. The primary clinical outcome measures were improvement in PTSD symptoms and dichotomously defined clinical responder status as measured by the CAPS at one-month follow-up. Additional outcome measures included self-reported measures of PTSD symptom severity, CAPS-2 symptom subscale scores, and morning plasma cortisol and ACTH levels. Results. Mifepristone was associated with significant improvements in total CAPS-2 score. At one-month follow-up, all four veterans in the mifepristone group and one of four veterans in the placebo group achieved clinical response; three of four veterans in the mifepristone group and one of four veterans in the mifepristone group remitted. Mifepristone treatment was associated with acute increases in cortisol and ACTH levels and decreases in cytosolic glucocorticoid receptor number in lymphocytes. Conclusions. Further controlled trials of the effects of mifepristone and their durability are indicated in PTSD. If effective, a short-term pharmacological treatment in PTSD could have myriad uses. 1. Introduction Within the last decade, two selective serotonin reuptake inhibitors (SSRIs), sertraline and paroxetine, have been approved by the FDA for the treatment of posttraumatic stress disorder (PTSD). In studies of civilian trauma survivors, each has been superior to placebo in achieving clinical response and reducing core PTSD symptoms, which represents a significant advance. However, their use as PTSD monotherapy has significant limitations. Even in the most favorable studies, some key symptoms are resistant to treatment (e.g., sleep disturbance), remission is uncommon, and continuous treatment is often necessary to prevent relapse. Additionally, SSRIs have been shown to be largely ineffective in combat veterans with PTSD. There is a need to develop better pharmacological treatments that specifically target PTSD symptoms and/or pathophysiology. Given the abundant evidence for hypothalamic-pituitary adrenal (HPA) axis dysregulation in PTSD, we performed a preliminary study to examine whether mifepristone¡ªwhich recalibrates the HPA axis through peripheral and central mechanisms¡ªcould be of therapeutic benefit. Mifepristone is a selective antagonist of glucocorticoid receptors (GRs) that induces increases in cortisol
%U http://www.hindawi.com/journals/drt/2012/393251/