Facilitating Fear-Based Memory Extinction With Dexamethasone: A Randomized Controlled Trial in Male Veterans With Combat-Related PTSD

Objective: Animal and preliminary human studies have demonstrated that glucocorticoids enhance the extinction of fear memories. Impaired extinction of fear memories is a critical component in the development and maintenance of posttraumatic stress disorder (PTSD). The purpose of this translational study was to determine the effectiveness of pairing a glucocorticoid with trauma memory reactivation as a novel intervention to treat PTSD and to measure the duration of the effect. Method: A total of 54 male veterans with combat-related PTSD in this double-blind, randomized, placebo-controlled trial received either four weekly glucocorticoid (dexamethasone [DEX]) or placebo administrations paired with a 45-second trauma memory reactivation task. PTSD and depressive symptom severity were assessed at baseline and at one three, and six months. Results: Trauma memory activation paired with DEX versus trauma memory activation paired with placebo demonstrated a significantly greater reduction of PTSD symptoms for DEX at the one-month (p =.037) and three-month (p =.036) posttreatment assessments, but the difference was no longer evident at six months. DEX showed a nonsignificantly greater reduction of PTSD symptoms than placebo over the course of the study (p =.067). Significantly more veterans in the DEX group lost their diagnosis of PTSD at one month posttreatment compared to the placebo group, but the difference was not maintained at three or six months. DEX had no effect on depression symptoms. Conclusions: Despite insufficient power to test differences in PTSD symptom reduction, findings suggest that this novel intervention may have potential for treatment of combat-related PTSD.