Adjunctive Medications and Outcomes from Virtual Reality Exposure Therapy

Summary and Comment |
May 5, 2014

Adjunctive Medications and Outcomes from Virtual Reality Exposure Therapy

  1. Joel Yager, MD

In Iraq and Afghanistan combat veterans with PTSD, alprazolam reduced treatment effectiveness, and D-cycloserine added virtually little.

  1. Joel Yager, MD

Exposure therapy is a standard approach to achieve fear extinction in post-traumatic stress disorder (PTSD), but whether adjunctive medications can further help remains unclear. Pre-exposure administration of d-cycloserine, an N-methyl-d-aspartate receptor partial agonist, has variably improved results in some anxiety disorders, presumably by boosting fear extinction, whereas benzodiazepines, widely used in PTSD patients, may impede fear extinction. To learn more, investigators randomized 156 Iraq or Afghanistan combat veterans diagnosed with PTSD to d-cycloserine (50 mg), alprazolam (0.25 mg), or placebo, each administered in a single pill 30 minutes before each of five 90-minute sessions of virtual reality exposure (VRE). VRE, which uses sights, sounds, vibrations, and odors, can augment prolonged imaginal exposure, an empirically supported therapy for PTSD.

Study exclusion criteria were lifetime psychosis, bipolar disorder, suicidal risk, and current alcohol or drug dependence. Patients with mild traumatic brain injury or ongoing treatment with stable nonbenzodiazepine psychotropics could participate. At 12 months post-treatment, all patients had improved, but those taking alprazolam did worse than those receiving placebo or d-cycloserine; 12-month results for the latter two were indistinguishable. Secondary analyses suggested that d-cycloserine reduced fear-potentiated startle, lowered cortisol responses to VR scenes, and modestly helped patients in between-session learning; however, these effects did not appear to improve global outcomes.


Because this study lacked a sham or no treatment group, the comparative effectiveness of the approach used here cannot be evaluated. Furthermore, traumatic brain injury and other psychotropic medication use may have been influential but were not considered in group assignments. Although we might agree that the clinically unimpressive results from d-cycloserine are at best inconclusive, clinicians have a clear take-home message: Benzodiazepines can interfere with imaginal exposure therapy for PTSD.

Editor Disclosures at Time of Publication

  • Disclosures for Joel Yager, MD at time of publication Grant /research support AHRQ Editorial boards Bulletin of the Menninger Clinic; Eating Disorders: Journal of Treatment and Prevention; Eating Disorders Review (Editor-in-Chief); International Journal of Eating Disorders; UpToDate; FOCUS: The Journal of Lifelong Learning in Psychiatry Leadership positions in professional societies American Psychiatric Association (Chair, Council of Quality Care)


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