Augmenting treatment efficiency in exposure therapy for PTSD: a randomized double-blind placebo-controlled trial of yohimbine HCl

AbstractThe alpha-2 adrenergic receptor antagonist, yohimbine, can facilitate fear extinction in animals and humans. One potential mechanism is increased noradrenergic activity and associated arousal in the presence of conditioned stimuli. Accordingly, yohimbine might augment prolonged exposure (PE) therapy for posttraumatic stress disorder (PTSD), where heightened exposure-oriented arousal is a theorized driver and empirical predictor of treatment success. A double-blind placebo-controlled randomized trial (NCT 01031979) piloted yohimbine augmentation in 26 males with combat-related PTSD. Participants were given one-time dose of yohimbine or placebo prior to the first imaginal exposure. Subsequently, both arms completed standard PE. The primary outcome was trauma-cued heart-rate reactivity a week after the drug/exposure visit, a highly specified, objective measure sensitive to incremental change. Secondary outcomes included arousal during the drug/exposure visit and slope of distress, PTSD, and depressio...