Targeting memory reconsolidation to prevent the return of fear in patients with fear of flying.

BACKGROUND: When a memory is recalled, it may again exist in a labile state and stored information becomes amenable to change, a psychobiological process known as reconsolidation. Exposure therapy for anxiety disorders involves accessing a fear memory and modifying it with less fearful information. A preclinical study reported that providing a reminder of a fear memory 10 min prior to extinction training in humans decreased fear up to 1 year later (Schiller et al., 2010). METHODS: For this pilot clinical study, we used virtual reality exposure therapy (VRE) for fear of flying (FoF) to determine if using a cue to reactivate the memory of the feared stimulus 10 min prior to exposure sessions leads to fewer anxiety-related behaviors and a more durable response compared to a neutral cue. FoF participants (N = 89) received four sessions of anxiety management training followed by four sessions of VRE. Participants were randomly assigned to receive an FoF cue (reactivation group) or a neutral cue (control group) prior to the VRE sessions. Heart rate (HR) and skin conductance levels (SCLs) were collected during posttreatment and 3-month follow-up assessments as objective markers of fear responding. RESULTS: Treatment was effective and all clinical measures improved equally between groups at posttreatment with maintained gains through follow-ups. Significant differences were identified with regard to HR and SCL indices. CONCLUSIONS: These results suggest that memory reactivation prior to exposure therapy did not have an impact on clinical measures but may enhance the effect of exposure therapy at the physiological level.

CRITICAL ANALYSIS OF THE CURRENT TREATMENT GUIDELINES FOR COMPLEX PTSD IN ADULTS.

According to current treatment guidelines for Complex PTSD (cPTSD), psychotherapy for adults with cPTSD should start with a "stabilization phase." This phase, focusing on teaching self-regulation strategies, was designed to ensure that an individual would be better able to tolerate trauma-focused treatment. The purpose of this paper is to critically evaluate the research underlying these treatment guidelines for cPTSD, and to specifically address the question as to whether a phase-based approach is needed. As reviewed in this paper, the research supporting the need for phase-based treatment for individuals with cPTSD is methodologically limited. Further, there is no rigorous research to support the views that: (1) a phase-based approach is necessary for positive treatment outcomes for adults with cPTSD, (2) front-line trauma-focused treatments have unacceptable risks or that adults with cPTSD do not respond to them, and (3) adults with cPTSD profit significantly more from trauma-focused treatments when preceded by a stabilization phase. The current treatment guidelines for cPTSD may therefore be too conservative, risking that patients are denied or delayed in receiving conventional evidence-based treatments from which they might profit.

Early interventions for PTSD: a review.

The high prevalence of trauma exposure and subsequent negative consequences for both survivors and society as a whole emphasize the need for secondary prevention of posttraumatic stress disorder. However, clinicians and relief workers remain limited in their ability to intervene effectively in the aftermath of trauma and alleviate traumatic stress reactions that can lead to chronic PTSD. The scientific literature on early intervention for PTSD is reviewed, including early studies on psychological debriefing, pharmacological, and psychosocial interventions aimed at preventing chronic PTSD. Studies on fear extinction and memory consolidation are discussed in relation to PTSD prevention and the potential importance of immediate versus delayed intervention approaches and genetic predictors are briefly reviewed. Preliminary results from a modified prolonged exposure intervention applied within hours of trauma exposure in an emergency room setting are discussed, along with considerations related to intervention reach and overall population impact. Suggestions for future research are included. Prevention of PTSD, although currently not yet a reality, remains an exciting and hopeful possibility with current research approaches translating work from the laboratory to the clinic.

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.

Changes in trauma-potentiated startle, skin conductance, and heart rate within prolonged exposure therapy for PTSD in high and low treatment responders.

While exposure-based psychotherapy is recommended as a first-line treatment for posttraumatic stress disorder (PTSD) given strong evidence for its effectiveness, some patients fail to receive full benefit. Psychophysiological data may be important complementary indices for investigating variability in treatment response and changes over the course of treatment. The focus of the present investigation was to examine change in psychophysiological indices pre- to post-treatment and to investigate if changes differed for high versus low PTSD treatment responders. Participants included veterans with primary PTSD diagnoses who received a two-week intensive prolonged exposure (PE) treatment. Psychophysiological assessment included trauma-potentiated startle, heart rate, and skin conductance recordings during presentation of three standard virtual reality (VR)-based, trauma-relevant scenes presented through a head mounted display. Results indicate that 48.6% were classified as high treatment responders (≥50% reduction in PCL-5 from baseline). Trauma-potentiated startle was observed in all patients at pre-treatment, F = 13.58, p < .001, in that startle magnitude was increased during VR stimuli relative to baseline regardless of responder status. However, in high treatment responders, there was an interaction of VR with time, F = 14.10, p = .001; VR scenes did not potentiate startle post-treatment. Specifically, high treatment responders were less reactive to trauma stimuli following PE treatment. There was no effect of time in the low responder group. Heart rate reactivity data revealed a significant main effect of treatment, F = 45.7, p = .035, but no significant interaction with responder status. Skin conductance reactivity did not significantly change from pre to post-treatment. These results suggest that trauma-potentiated startle may represent an objective marker of fear- and anxiety-related symptom reduction that is sensitive to both traditional outpatient as well as intensive treatment approaches.

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.

Virtual Reality-Enhanced Extinction of Phobias and Post-Traumatic Stress.

Virtual reality (VR) refers to an advanced technological communication interface in which the user is actively participating in a computer-generated 3-dimensional virtual world that includes computer sensory input devices used to simulate real-world interactive experiences. VR has been used within psychiatric treatment for anxiety disorders, particularly specific phobias and post-traumatic stress disorder, given several advantages that VR provides for use within treatment for these disorders. Exposure therapy for anxiety disorder is grounded in fear-conditioning models, in which extinction learning involves the process through which conditioned fear responses decrease or are inhibited. The present review will provide an overview of extinction training and anxiety disorder treatment, advantages for using VR within extinction training, a review of the literature regarding the effectiveness of VR within exposure therapy for specific phobias and post-traumatic stress disorder, and limitations and future directions of the extant empirical literature.

A preliminary report on the use of virtual reality technology to elicit craving and cue reactivity in cocaine dependent individuals.

In the present feasibility study, we developed a 3-dimensional virtual "crack" cocaine environment and evaluated the environment's ability to elicit subjective craving and cue reactivity (i.e., subjective emotional responding, heart rate and skin conductance) in 11 crack cocaine dependent individuals. Each of the seven 3-D crack cocaine scenes in the cocaine environment depicted actors engaging in a range of using-related behaviors (i.e., smoking crack) whereas the neutral environment contained scenes depicted 3-D aquariums with active aquatic life (baseline measures were obtained following immersion in the neutral environment). Results indicated that craving was significantly elevated during the cocaine-related scenes as compared to baseline. Craving varied by scene content, with scenes depicting active cocaine use eliciting the highest levels of craving. Heart rate was significantly higher in four of the scenes with drug use content and positive affect (i.e., happiness) ratings were significantly lower during cocaine scenes as compared to baseline. Overall, the results suggest that a standardized and stimulus rich virtual reality environment effectively elicits craving and physiologic reactivity. Such technology has potential utility in the development and refinement of exposure-based behavioral and pharmacological interventions for substance use disorders.

Virtual reality exposure therapy and standard (in vivo) exposure therapy in the treatment of fear of flying.

This controlled clinical trial tested virtual reality exposure (VRE) therapy for the fear of flying (FOF), a relatively new and innovative way to do exposure therapy, and compared it to standard (in vivo) exposure therapy (SE) and a wait list (WL) control with a 6- and 12-month follow-up. Eighty-three participants with FOF were randomly assigned to VRE, SE, or WL. Seventy-five participants, 25 per group, completed the study. Twenty-three WL participants completed randomly assigned treatment following the waiting period. Treatment consisted of 4 sessions of anxiety management training followed either by exposure to a virtual airplane (VRE) or an actual airplane at the airport (SE) conducted over 6 weeks. Results indicate that VRE was superior to WL on all measures, including willingness to fly on the posttreatment flight (76% for VRE and SE; 20% for WL). VRE and SE were essentially equivalent on standardized questionnaires, willingness to fly, anxiety ratings during the flight, self-ratings of improvement, and patient satisfaction with treatment. Follow-up assessments at 6 and 12 months indicated that treatment gains were maintained, with more than 70% of respondents from both groups reporting continued flying at follow-up. Based on these findings, the use of VRE in the treatment of FOF was supported in this controlled study, suggesting that experiences in the virtual world can change experiences in the real world.

Cognitive behavior therapy for fear of flying: sustainability of treatment gains after September 11.

This study examines the long-term efficacy of cognitive-behavioral therapy (CBT) for fear of flying (FOF) after a catastrophic fear-relevant event, the September 11, 2001, terrorist attacks. Participants (N = 115) were randomly assigned to and completed treatment for FOF using 8 sessions of either virtual reality exposure therapy (VRE) or standard exposure therapy (SE) prior to September 11, 2001. Individuals were reassessed in June, 2002, an average of 2.3 years after treatment, with a response rate of 48% (n = 55). Analyses were run on the original data and, using multiple imputation procedures, on imputed data for the full sample. Individuals maintained or improved upon gains made in treatment as measured by standardized FOF questionnaires and by number of flights taken. There were no differences between VRE and SE. Thus, results suggest that individuals previously treated for FOF with cognitive-behavioral therapy can maintain treatment gains in the face of a catastrophic fear-relevant event, even years after treatment is completed.

Risperidone in psychotic combat-related posttraumatic stress disorder: an open trial.

RATIONALE: Psychotic symptoms that frequently occur in combat-related posttraumatic stress disorder (PTSD) complicate its pharmacotherapy. We hypothesized that war veterans with psychotic PTSD, resistant to prior antidepressant treatment, would respond well to 6 weeks of treatment with the atypical antipsychotic risperidone, given as a monotherapy. METHOD: Twenty-six male war veterans with psychotic PTSD (DSM-IV) completed the 6-week inpatient treatment with risperidone (2-4 mg/day) during the period from November 1999 through December 2002. The primary outcome measure was change from baseline to endpoint (6 weeks) in Positive and Negative Syndrome Scale (PANSS) total and subscale scores. Secondary outcome measures were changes in PTSD Interview (PTSD-I) and Clinical Global Impressions-Severity of Illness scale (CGI-S) total and subscale scores. Clinical improvement was assessed by CGI-S, CGI-Improvement scale, and Patient Global Impression of Improvement scale, while adverse events were recorded by Drug-Induced Extrapyramidal Symptoms Scale. RESULTS: Treatment with risperidone for either 3 or 6 weeks in an open trial significantly reduced total and subscales scores on the PANSS and on the PTSD-I and CGI-S when compared to baseline scores in patients with psychotic PTSD. CONCLUSION: Our preliminary data from the open trial indicate that risperidone decreased most of the psychotic and PTSD symptoms. Psychotic PTSD patients, unresponsive to antidepressant treatment, improved significantly after treatment for either 3 or 6 weeks with risperidone.

Applying learning principles to the treatment of post-trauma reactions.

Posttraumatic stress disorder (PTSD) can be characterized as a failure of recovery caused, in part, by a failure of fear extinction after trauma. By studying the process of extinction, we can be informed regarding the etiology and maintenance of PTSD. The normal response to trauma in humans includes a set of predictable reactions including reexperiencing, avoidance, and hyperarousal that typically extinguish in the days and weeks after the trauma. In the majority of people exposed to trauma, these responses extinguish over time. However, in a substantial minority, extinction fails and these persisting responses become the symptoms of PTSD. Therefore, one of our fundamental hypotheses is that PTSD is a disorder caused in part by the failure of extinction of predictable posttraumatic physiological and psychological reactions. The most empirically validated treatments for PTSD involve exposure of the patient to trauma-related cues in the absence of danger that then lead to the extinction of these reexperiencing, avoidance, and arousal symptoms. There is also mounting evidence that individuals with PTSD are more resistant to extinction. Regarding early interventions with traumatized individuals, there is mounting evidence that some early one-time interventions actually may impede extinction, whereas interventions delivered in more than one session, at least several weeks after the trauma, to individuals continuing to experience above average reactions, generally are effective in preventing the development of PTSD. Thus, there appears to be an interaction between timing of the intervention, number of intervention sessions, and either arousal level and/or risk status in determining whether the intervention will be helpful, harmful, or neutral.

A pilot and feasibility study of virtual reality as a distraction for children with cancer.

OBJECTIVE: To pilot and test the feasibility of a novel technology to reduce anxiety and pain associated with an invasive medical procedure in children with cancer. METHOD: Children with cancer (ages 7-19) whose treatment protocols required access of their subcutaneous venous port device (port access) were randomly assigned to a virtual reality distraction intervention, a non-virtual reality distraction, or treatment as usual without a distraction. The researchers obtained assessments of the child's pain and anxiety from the parent, child, and unblinded nurses. Pulse rate was monitored throughout the procedure, and behavioral indices of distress were recorded, as observed by the researchers. RESULTS: Reductions in pain and anxiety were found for children who used the virtual reality distraction in comparison with the no distraction condition as evidenced by lower pulse rate and reports of pain by nurses. No significant differences were found for the non-virtual reality condition versus the no distraction condition on pulse rate. CONCLUSIONS: These findings suggest that virtual reality may be a useful tool for distraction during painful medical procedures, but further studies are needed to test potential efficacy and feasibility during other, more distressing medical procedures with larger sample sizes.

Twelve-month follow-up of virtual reality and standard exposure therapies for the fear of flying.

This study reports the 12-month follow-up from patients with the fear of flying who were treated in a controlled study and randomly assigned (n = 49) to virtual reality exposure (VRE) therapy, standard exposure (SE) therapy, or to a wait-list control (WL). VRE and SE were equally superior to WL. At 12 months posttreatment, data were gathered on 24 of the 30 (80%) patients who were assigned to VRE or SE. Patients maintained their treatment gains, and 92% of VRE participants and 91% of SE participants had flown on a real airplane since the graduation flight. This is the 1st year-long follow-up of patients having been treated with VRE and indicates that short-term treatment can have lasting effects.

Use of virtual reality as a distractor for painful procedures in a patient with pediatric cancer: a case study.

Virtual reality (VR) has been demonstrated as an effective tool to help people overcome a variety of anxiety disorders. In this case study, the use of VR as a distractor to alleviate pain and anxiety associated with an invasive medical procedure for a pediatric cancer patient was explored. An A-B-C-A design during four consecutive medical appointments in an outpatient oncology clinic compared no distraction (A), non-VR distraction on a computer screen (B), and VR distraction with a head set (C). Behavioral observations of distress by the researcher and reports of pain and anxiety by the patient, parent, and nurse were taken before and during the procedure. The child's pulse was monitored throughout the procedure. The findings from this case study suggest benefit from using VR distraction, as indicated by lower pain and anxiety ratings, reduced pulse, and fewer observed behavioral indices of distress. The need for larger scale studies and application of VR with younger children is discussed in the context of confirming effectiveness of this technique and providing more generalizable information about efficacy.

Exposure therapy for posttraumatic stress disorder.

Exposure therapy is a well-established treatment for Posttraumatic Stress Disorder (PTSD) that requires the patient to focus on and describe the details of a traumatic experience. Exposure methods include confrontation with frightening, yet realistically safe, stimuli that continues until anxiety is reduced. A review of the literature on exposure therapy indicates strong support from well-controlled studies applied across trauma populations. However, there are many misconceptions about exposure therapy that may interfere with its widespread use. These myths and clinical guidelines are addressed. It is concluded that exposure therapy is a safe and effective treatment for PTSD when applied as directed by experienced therapists.

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.

Early intervention may prevent the development of posttraumatic stress disorder: a randomized pilot civilian study with modified prolonged exposure.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a major public health concern with long-term sequelae. There are no accepted interventions delivered in the immediate aftermath of trauma. This study tested an early intervention aimed at modifying the memory to prevent the development of PTSD before memory consolidation. METHODS: Patients (n = 137) were randomly assigned to receive three sessions of an early intervention beginning in the emergency department compared with an assessment only control group. Posttraumatic stress reactions (PTSR) were assessed at 4 and 12 weeks postinjury and depression at baseline and week 4. The intervention consisted of modified prolonged exposure including imaginal exposure to the trauma memory, processing of traumatic material, and in vivo and imaginal exposure homework. RESULTS: Patients were assessed an average of 11.79 hours posttrauma. Intervention participants reported significantly lower PTSR than the assessment group at 4 weeks postinjury, p < .01, and at 12 weeks postinjury, p < .05, and significantly lower depressive symptoms at week 4 than the assessment group, p < .05. In a subgroup analysis, the intervention was the most effective at reducing PTSD in rape victims at week 4 (p = .004) and week 12 (p = .05). CONCLUSIONS: These findings suggest that the modified prolonged exposure intervention initiated within hours of the trauma in the emergency department is successful at reducing PTSR and depression symptoms 1 and 3 months after trauma exposure and is safe and feasible. This is the first behavioral intervention delivered immediately posttrauma that has been shown to be effective at reducing PTSR.

Comparing virtual reality exposure therapy to present-centered therapy with 11 U.S. Vietnam veterans with PTSD.

Eleven Vietnam veterans with war-related posttraumatic stress disorder (PTSD) were randomly assigned to 10 sessions of either virtual reality exposure (VRE) therapy within a computer-generated virtual Vietnam environment or present-centered therapy (PCT) that avoided traumatic content and utilized a problem-solving approach. Participants were assessed at pretreatment, posttreatment, and 6 months posttreatment by an independent assessor blind to treatment condition. Nine participants completed treatment with one dropout per condition. No significant differences emerged between treatments, likely due to insufficient power. Although comparison of mean changes in PTSD symptoms for the VRE and PCT conditions yielded a moderate effect size (d = 0.56) in favor of VRE at 6 months posttreatment, changes in PTSD scores were more variable, and therefore less reliable, within the VRE condition. The utility of VRE with older veterans with PTSD is discussed.