A Randomized, Double-Blind Evaluation of D-Cycloserine or Alprazolam Combined With Virtual Reality Exposure Therapy for Posttraumatic Stress Disorder in Iraq and Afghanistan War Veterans

• Type of Material: Article
• Authors: Barbara Rothbaum, Emory University; Matthew Price, University of Vermont; Tanja Jovanovic, Emory University; Seth Norrholm, Emory University; Maryrose Gerardi, Emory University; Boadie Dunlop, Emory University; Michael Davis, Emory University; Bekh Bradley-Davino, Emory University; Erica Duncan, Emory University; Albert Rizzo, University of Southern California; Kerry Ressler, Emory University
• Language: English
• Date: 2014-06-01
• Publisher: American Psychiatric Publishing
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 American Psychiatric Association
• Final Published Version (URL): http://dx.doi.org/10.1176/appi.ajp.2014.13121625
• Title of Journal or Parent Work: American Journal of Psychiatry
• ISSN: 0002-953X
• Volume: 171
• Issue: 6
• Start Page: 640
• End Page: 648
• Grant/Funding Information: This study was supported by National Institute of Mental Health, Grant No. 1R01MH70880-01-A2, “A Cognitive Enhancer may Facilitate Behavioral Exposure Therapy” awarded to Dr. Rothbaum.; Dr. Rothbaum also has funding from Department of Defense Clinical Trial Grant No.W81XWH-10-1-1045, “Enhancing Exposure Therapy for PTSD: Virtual Reality and Imaginal Exposure with a Cognitive Enhancer”, National Institute of Mental Health, Grant No. 5 U19 MH069056-03, “The Emory-MSSM-GSK-NIMH Collaborative Mood and Anxiety Disorders Initiative,” National Institute of Mental Health, Grant No. 1R01MH70880-01-A2, “A Cognitive Enhancer may Facilitate Behavioral Exposure Therapy,” NIH Grant No. 1R01MH094757-01, “Prospective Determination of Psychobiological Risk Factors for Posttraumatic Stress,” Brain and Behavior Research Foundation (NARSAD) Distinguished Investigator Grant, “Optimal Dose of early intervention to prevent PTSD”, and McCormick Foundation “Brave Heart: MLB’s Welcome Back Veterans SouthEast Initiative,” and recent previous support from Transcept Pharmaceuticals “A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study To Evaluate The Efficacy And Safety Of Low-Dose Ondansetron For Adjunctive Therapy In Adult Patients With Obsessive-Compulsive Disorder Who Have Not Adequately Responded To Treatment With A Serotonin Reuptake Inhibitor.”
• Keywords: Science & Technology; AUGMENTATION; EXTINCTION; PLACEBO-CONTROLLED TRIAL; SOCIAL ANXIETY DISORDER; Psychiatry; Life Sciences & Biomedicine; CONDITIONED FEAR; SESSIONS; OBSESSIVE-COMPULSIVE DISORDER; ENHANCEMENT; BEHAVIOR-THERAPY; FACILITATION
• Research Categories: Psychology, Behavioral

Abstract

Objective: The authors examined the effectiveness of virtual reality exposure augmented with D-cycloserine or alprazolam, compared with placebo, in reducing posttraumatic stress disorder (PTSD) due to military trauma. Method: After an introductory session, five sessions of virtual reality exposure were augmented with D-cycloserine (50 mg) or alprazolam (0.25 mg) in a double-blind, placebo-controlled randomized clinical trial for 156 Iraq and Afghanistan war veterans with PTSD. Results: PTSD symptoms significantly improved from pre- to posttreatment across all conditions and were maintained at 3, 6, and 12months. Therewere no overall differences in symptomsbetween D-cycloserine and placebo at any time. Alprazolam and placebo differed significantly on the Clinician-Administered PTSD Scale score at posttreatment and PTSD diagnosis at 3 months posttreatment; the alprazolam group showed a higher rate of PTSD (82.8%) than the placebo group (47.8%). Between-session extinction learning was a treatment-speci fic enhancer of outcome for the D-cycloserine group only. At posttreatment, the D-cycloserine group had the lowest cortisol reactivity and smallest startle response during virtual reality scenes. Conclusions: A six-session virtual reality treatment was associated with reduction in PTSD diagnoses and symptoms in Iraq and Afghanistan veterans, although there was no control condition for the virtual reality exposure. There was no advantage of D-cycloserine for PTSD symptoms in primary analyses. In secondary analyses, alprazolam impaired recovery and D-cycloserine enhanced virtual reality outcome in patients who demonstrated within-session learning. D-Cycloserine augmentation reduced cortisol and startle reactivity more than did alprazolam or placebo, findings that are consistent with those in the animal literature.