Dose timing of D-cycloserine to augment cognitive behavioral therapy for social anxiety: Study design and rationale

Abstract

The use of D-cycloserine (DCS) as a cognitive enhancer to augment exposure-based cognitive-behavioral therapy (CBT) represents a promising new translational research direction with the goal to accelerate and optimize treatment response for anxiety disorders. Some studies suggest that DCS may not only augment extinction learning but could also facilitate fear memory reconsolidation. Therefore, the effect of DCS may depend on fear levels reported at the end of exposure sessions. This paper presents the rationale and design for a randomized controlled trial examining the relative efficacy of tailoring DCS administration based on exposure success (i.e. end fear levels) during a 5-session group CBT protocol for social anxiety disorder (n = 156). Specifically, tailored post-session DCS administration will be compared against untailored post-session DCS, untailored pre-session DCS, and pill placebo in terms of reduction in social anxiety symptoms and responder status. In addition, a subset of participants (n = 96) will undergo a fear extinction retention experiment prior to the clinical trial in which they will be randomly assigned to receive either DCS or placebo prior to extinguishing a conditioned fear. The results from this experimental paradigm will clarify the mechanism of the effects of DCS on exposure procedures. This study aims to serve as the first step toward developing an algorithm for the personalized use of DCS during CBT for social anxiety disorder, with the ultimate goal of optimizing treatment outcome for anxiety disorders.

Trial registration: ClinicalTrials.gov NCT02066792.

Keywords: Cognitive–behavioral therapy; Exposure therapy; Social anxiety disorder; Social phobia; d-cycloserine.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1

Schematic depiction of the fear extinction retention paradigm. In each phase, participants view a computer monitor with an image of a room containing an unlit lamp for 6 seconds. The lamp then lights up to one of two colors for 12 seconds. During conditioning, one color of the lamp (CS+) is paired with a 500 ms electric shock in context 1. During extinction training, the CS+ is presented in context 2 without the US, as is the CS- (not shown). This procedure is repeated in context 2 during extinction recall, and in context 1 during renewal.