title: 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.
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, 648 Beacon Street, 6th, Floor Boston, MA 02215, United States. Electronic address: shofmann@bu.edu.
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Hofmann
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, 648 Beacon Street, 6th, Floor Boston, MA 02215, United States. Electronic address: jcarpen@bu.edu.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Carpenter
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, 648 Beacon Street, 6th, Floor Boston, MA 02215, United States. Electronic address: mwotto@bu.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Otto
authors.affiliation: Department of Psychology, Southern Methodist Univeristy, Expressway Tower 1100N, Dallas, TX 75275, United States. Electronic address: drosenfi@smu.edu.
authors.forename: David
authors.initials: D
authors.lastname: Rosenfield
authors.affiliation: Department of Psychology, University of Texas at Austin, 108 E. Dean Keeton, Stop A8000, Austin, TX 78712, United States. Electronic address: smits@utexas.edu.
authors.forename: Jasper A J
authors.initials: JA
authors.lastname: Smits
authors.affiliation: Department of Psychiatry, Rush University Medical Center, 1645W. Jackson Blvd, Suite 600, Chicago, IL 60612, United States. Electronic address: mark_pollack@rush.edu.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Pollack
mesh_terms: D001008:Anxiety Disorders / Q000628:therapy*; D003131:Combined Modality Therapy; D003523:Cycloserine / Q000627:therapeutic use*; D004311:Double-Blind Method; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007171:Implosive Therapy / Q000379:methods*; D011569:Psychiatric Status Rating Scales; D012107:Research Design; D012463:Saliva / Q000737:chemistry; D012720:Severity of Illness Index; D012890:Sleep
chemical_list: D003523:Cycloserine; D006854:Hydrocortisone
keywords: Cognitive–behavioral therapy; Exposure therapy; Social anxiety disorder; Social phobia; d-cycloserine