Maryrose Gerardi

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

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 12 months. There were no overall differences in symptoms between 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-specific 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.

Virtual Reality Exposure Therapy Using a Virtual Iraq: Case Report

Posttraumatic stress disorder (PTSD) has been estimated to affect up to 18% of returning Operation Iraqi Freedom (OIF) veterans. Soldiers need to maintain constant vigilance to deal with unpredictable threats, and an unprecedented number of soldiers are surviving serious wounds. These risk factors are significant for development of PTSD; therefore, early and efficient intervention options must be identified and presented in a form acceptable to military personnel. This case report presents the results of treatment utilizing virtual reality exposure (VRE) therapy (virtual Iraq) to treat an OIF veteran with PTSD. Following brief VRE treatment, the veteran demonstrated improvement in PTSD symptoms as indicated by clinically and statistically significant changes in scores on the Clinician Administered PTSD Scale (CAPS; Blake et al., 1990) and the PTSD Symptom Scale Self-Report (PSS-SR; Foa, Riggs, Dancu, & Rothbaum, 1993). These results indicate preliminary promise for this treatment.

Virtual Reality Exposure Therapy for Post-Traumatic Stress Disorder and Other Anxiety Disorders

Anxiety disorders, including phobias and post-traumatic stress disorder, are common and disabling disorders that often involve avoidance behavior. Cognitive-behavioral treatments, specifically imaginal and in vivo forms of exposure therapy, have been accepted and successful forms of treatment for these disorders. Virtual reality exposure therapy, an alternative to more traditional exposure-based therapies, involves immersion in a computer-generated virtual environment that minimizes avoidance and facilitates emotional processing. In this article, we review evidence on the application of virtual reality exposure therapy to the treatment of specific phobias and post-traumatic stress disorder and discuss its advantages and cautions.

Virtual Reality Exposure Therapy for Combat-Related PTSD

War is perhaps one of the most challenging situations that a human being can experience. The physical, emotional, cognitive, and psychological demands of a combat environment place enormous stress on even the best-prepared military personnel. Numerous reports indicate that the incidence of posttraumatic stress disorder (PTSD) in returning Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) military personnel is significant. This has served to motivate research on how to better develop and disseminate evidence-based treatments for PTSD that leverage the unique features available with virtual reality (VR) technology. VR-delivered exposure therapy for PTSD is currently being used to treat combat- and terrorist attack-related PTSD with initial reports of positive outcomes. This chapter presents a brief overview and rationale for the use of VR exposure for combat-related PTSD and describes the Virtual Iraq/Afghanistan exposure therapy system. This includes a short review of the previous literature, a description of the system components and the treatment protocol, and a case presentation. VR offers an alternative format for delivering exposure-based therapies for PTSD that may appeal to certain service members and veterans who grew up “digital” and who might be inclined to seek treatment in this fashion.

D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Individual Participant Data

Importance Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, −3.62; 95% CI, −0.81 to −6.43; P = .01; d = −0.25) but not from pretreatment to midtreatment (mean difference, −1.66; 95% CI, −4.92 to 1.60; P = .32; d = −0.14) or from pretreatment to follow-up (mean difference, −2.98, 95% CI, −5.99 to 0.03; P = .05; d = −0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.

Pharmacological Enhancement of Behavioral Therapy: Focus on Posttraumatic Stress Disorder

Improved efficacy in the treatment of posttraumatic stress disorder (PTSD) and other anxiety disorders is urgently needed. Traditional anxiety treatments of hypnosis and psychodynamic therapy may be of some help, but uncontrolled studies lead to inconclusive results on the efficacy of these treatment techniques. There is a larger literature supporting the efficacy of cognitive-behavioral procedures with PTSD, including prolonged exposure therapy, eye movement desensitization and reprocessing, and anxiety management techniques. The cutting-edge technology of virtual reality-based exposure therapy for PTSD is particularly exciting. To further build on effective psychosocial treatments, current pharmacological augmentation approaches to emotional learning are being combined with psychotherapy. In particular, D-cycloserine, a partial NMDA agonist, has shown to be effective in facilitating the exposure/extinction therapy to improve the efficacy of treating anxiety disorders, and may guide the way for new pharmacological enhancements of behavioral therapy.

Pharmacological Innovations for Posttraumatic Stress Disorder and Medication- Enhanced Psychotherapy

Posttraumatic stress disorder (PTSD) is a common condition for which existing treatments are ineffective for many patients. Recent discoveries in the neurobiology of learning and memory, along with expanding knowledge of how those systems are impacted by the biology of the stress response, have opened new arenas for potential medication treatments for PTSD. We conducted a review of registered clinical trials investigating the efficacy of new agents for PTSD. The glucocoritcoid and adrenergic signaling systems are the most frequent targets of these investigational approaches to the prevention and treatment of PTSD. Additional trials are evaluating modulation of other CNS targets, including neurosteroids, glutamate, gamma-amino butyric acid, endocannabinoids, oxytocin, neurokinin/Substance P, and dopamine. A particularly exciting area of research is studies examining Medication-Enhanced Psychotherapy (MEP). Medications provided before or after exposure therapy for PTSD can enhance outcomes by: 1) strengthening learning and memory of fear extinction; 2) disrupting reconsolidation, thereby weakening fear memories; or 3) facilitating engagement in psychotherapy by reducing fear and enhancing openness to experience. The next few years promise to produce insight into the neurobiology and clinical efficacy of several novel approaches in the pharmacologic treatment and prevention of PTSD.

A pilot study of an exposure-based intervention in the ED designed to prevent posttraumatic stress disorder

Early interventions to prevent PTSD have been limited in scope and effectiveness. This pilot study examines the feasibility and preliminary effectiveness of a model for brief preventive intervention: 1-session individualized exposure-based therapy delivered in the emergency department (ED). Eligible patients who experienced exposure to a traumatic event in the previous 24 hours were screened and assigned to assessment-only (n = 5) or intervention (imaginal exposure, n = 5) conditions. Both groups returned for 1-week follow-up. Results indicate that patients receiving this intervention reported slightly decreased levels of depression at 1-week follow-up and were rated lower on clinician-rated global severity of symptoms than patients in the assessment-only condition. The level of subject participation and ED staff support in this pilot study argues for feasibility of data collection, intervention, and follow-up with this population. Results also offer evidence that the intervention did not appear to harm participants and in fact may be helpful.

Cortisol Response Following Exposure Treatment for PTSD in Rape Victims

This study examined changes in salivary cortisol levels pre- to posttreatment in adult female rape victims diagnosed with posttraumatic stress disorder (PTSD) randomly assigned to be treated with either prolonged exposure therapy or eye movement desensitization and reprocessing. Salivary cortisol was collected at baseline, Session 3, and Session 9. A significant decrease in salivary cortisol levels was observed in individuals classified as treatment responders in both treatment conditions. Findings suggest that successful exposure-based treatments for PTSD that result in trauma-related and depressive symptom reduction may impact the action of the hypothalamic–pituitary–adrenal axis as measured by changes in level of salivary cortisol from pre- to posttreatment.

Virtual Reality Exposure for PTSD Due to Military Combat and Terrorist Attacks

Humans exposed to war and terrorist attacks are at risk for the development of posttraumatic stress disorder (PTSD). Numerous reports indicate that the incidence of PTSD in both returning Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) military personnel and survivors of the 9/11 World Trade Center (WTC) attacks is significant. These situations have served to motivate research on how to better develop and disseminate evidence-based treatments for PTSD and other related psychosocial conditions. Virtual reality (VR) delivered exposure therapy for PTSD is currently being used to treat combat and terrorist attack related PTSD with initial reports of positive outcomes. This paper presents an overview and rationale for the use of VR exposure therapy with anxiety disorders and PTSD and describes the status of two systems (Virtual Iraq/Afghanistan and Virtual World Trade Center) developed for this purpose.