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

Abstract

The 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 depression over the course of PE. Consistent with hypothesis, yohimbine led to higher objective and subjective arousal during the drug/exposure visit and to lower trauma-cued heart-rate reactivity one-week later. One dose of yohimbine also led to greater between-session habituation and more rapid improvement on depression, but not PTSD, over the course of care. Results of this controlled pilot indicate support for continued investigation of yohimbine-augmented exposure therapy for PTSD.

Keywords:

• Yohimbine
• PTSD
• prolonged exposure therapy
• extinction augmentation
• treatment augmentation
• RCT
• empirically-supported treatments
• evidence-based treatments
• biological markers
• psychophysiology

Acknowledgments

We would like to thank Bridgette Niepoth, MA for her invaluable help with recruitment, data collection, and management in this project and Dr Mark Bouton for key insights related to the translational research design.

Notes

1. Main analyses related to heart rate reactivity were also investigated for skin conductance reactivity, a measure which has also been found to show reductions subsequent to exposure therapy (Shalev et al., 1992; Wood et al., 2007). Detailed skin conductance measurement procedures have been previously published (Wangelin et al., 2013). Results indicated a similar though less robust pattern as the heart rate measure, with a marginally significant yohimbine augmentation effect for the ITT sample (t = −1.69, df = 1530, β = −.14, 95% CI: −.30, .02, p = .09), a highly significant effect for treatment responders (t = −2.93, df = 991, β = −.29, 95% CI: −.49, −.10, p = .003, d = .13), and no effect for non-responders.