Enhancing the Efficacy of Exposure Therapy: Translation of Pharmacological Augmentation of Fear Extinction

Fear extinction is foundational to exposure therapy and thus studying strategies to optimize fear extinction is relevant for clinical practice. This paper provides a critical review of translational research on pharmacological enhancement of fear extinction, concentrating mostly on D-cycloserine (DCS), the agent with the most extensive evidence base across levels of analyses. Despite early promise, results across preclinical, human laboratory, and clinical trials have been mixed. We identify factors that may account for these inconsistent findings, including differences in study design, selection of subjects, sample size, and measurement approaches. We emphasize the need for a rigorous mechanistic research agenda that assesses extinction processes – acquisition, consolidation, and retrieval – as distinct mechanistic targets, and examines the relation between changes in these fear extinction processes and clinical outcomes. Finally, we discuss opportunities to advance translational research in this area leveraging extant collaborative infrastructures to improve quality, efficiency and ultimately the availability of effective clinical strategies.