Prolonged Exposure Psychotherapy (PE)

OVERVIEW

Prolonged Exposure (PE) is a psychotherapy for Post-traumatic Stress Disorder (PTSD); it is one specific type of cognitive behavioral therapy (CBT). PE teaches the method of gradually approaching trauma-related memories, feelings, and situations that have been avoided since a trauma. Theoretically-based and highly efficacious, Prolonged Exposure is a first-line treatment for chronic PTSD and related depression, anxiety and anger.[1] Individuals work with their therapist in a safe, graduated fashion to face stimuli and situations that evoke fear and remind them of the trauma to increase their comfort and reduce their fear. Exposure is an intervention strategy commonly used in cognitive behavioral therapy to help individuals confront fears. After a significant trauma, most people seek to avoid anything that reminds them of the trauma they experienced; this avoidance actually reinforces their fear. By facing what has been avoided, a person can decrease symptoms of PTSD by actively learning that the trauma-related memories and subsequent cues are not dangerous and thus do not need to be avoided.[2]

Empirically validated with more than 20 years of research supporting its use, PE reduces the symptoms of PTSD, depression, anger, and anxiety in trauma survivors. Producing clinically significant improvement in 80% of patients with chronic PTSD, this CBT is currently used by practitioners throughout the world to successfully treat survivors of varied traumas (including rape, assault, child abuse, combat, motor vehicle accidents and disasters.) Further, this mode of treatment has been beneficial for those suffering from co-occurring PTSD and substance abuse when combined with substance abuse treatment. In 2001, Prolonged Exposure for PTSD received an Exemplary Substance Abuse Prevention Program Award from the U.S. Department of Health and Human Services Substance Abuse and Mental Health Services Administration (SAMHSA).[3]

Since its inception, PE has evolved into a flexible and adaptable program of intervention to address the individual needs of varied trauma survivors. In addition to reducing symptoms of PTSD, PE has been found to instill confidence, improve various aspects of daily functioning, increase the ability to cope with courage rather than fearfulness when facing stress, and improve one’s ability to discriminate safe and unsafe situations.[4] PE is now recommended as a first-line treatment in all major PTSD treatment guidelines, including: the American Psychological Association, the International Society for Traumatic Stress Studies (ISTSS), the United Kingdom's National Institute for Health and Care Excellence (NICE), the U.S. Department of Veterans Affairs and Department of Defense (VA, DoD) and the Australian Guidelines.[5]

Theoretical Model

Emotional Processing Theory (EPT) and the Learning Theory (LT) are two separate theories of PTSD. There is considerable overlap in the concepts from both theories, and the mechanisms of PE have been conceptualized using both theories.[6]

EPT proposes that pathological fear structures develop after trauma, leading to PTSD, and that these pathological fear structures need to be modified for recovery to occur. Fear structures are made up of a stimulus (people, places, things, memories), followed by an emotional and/or physiological response and thoughts regarding the meaning of the stimulus and response. Fear structures become pathological when someone who has experienced a trauma experiences a generally safe stimulus with considerable distress, thereby attributing extremely negative meanings about the self, others, or world. Despite being generally non-threatening, people with developed fear structures of PTSD feel the situation is too dangerous for them and they feel they cannot handle being in that situation.

The fear structure can become modified through exposure and habituation to the feared stimulus in a safe format. Exposure to the stimulus activates the fear structure and allows the client to learn that:

Memories and reminders of the trauma are not, themselves, dangerous and can actually be experienced without significant distress.
Distress is fleeting and is not ongoing.
Emotional responses can gradually reduce over time - even without doing anything.
Responses (such as heart racing) are actually not dangerous nor life-threatening.
The client has the ability to handle negative affect of exposure.

Recovery from PTSD occurs as the fear structure is modified in such a way that the once-feared stimuli no longer elicits extreme negative responses or meanings.[7]

The concept of extinction in Prolonged Exposure can be described in terms of extinction and relearning including contextualization of learning and memory.[8] When the full memory, including all the emotional and cognitive responses, is activated, updated information that is incompatible with the trauma memory can be incorporated (reconsolidated) into the memory structure. Extinction occurs in the context of repeated exposure to the feared stimulus and is marked by a reduction in physiological and emotional intensity of response to that stimulus.[9] New inhibitory associations are formed on top of one’s fear associations; there is then a reduction in subjective fear-response to the traumatic memory and its reminders. This relearning is facilitated through the process of contextualization: learning to discriminate between safety and threat cues, depending in the context in which they occur.[10] As cognitive and emotional processing changes that occur in tandem with extinction and relearning, one develops an increased sense of competence, reduced sense that the world as dangerous, and reduction in social and emotional withdrawal.[11,12]

EFFICACY

The psychological and physical changes a person experiences with PTSD can be explained biologically. The fear neurocircuitry consists of several brain structures including the amygdala, anterior cingulate cortex (ACC) and the ventromedial prefrontal cortex (vmPFC). The fear network is implicated in evaluating whether a stimulus should be approached or avoided; activity within this network is correlated with anxiety.[13] Evidence from fMRI studies indicates that the amygdala is overactive in persons with PTSD. As the amygdala receives sensory input and orchestrates the response to threatening signals, overactive responses in that of persons with PTSD likely contribute to the exaggerated fear response and re-experiencing symptoms.[14-16] Further, the vmPFC downregulates the amygdala and appears to play a critical role in extinction recall.[17] In PTSD, vmPFC is hypoactive, which projects less inhibitory input, contributing to the hyperactivation of the amygdala.[18-20] Further, the ACC and amygdala process aversive stimuli, leading to the peripheral nervous system to triggering a response; this response has been shown to be hyperactive during extinction recall in individuals with PTSD.[21,22] It is the afore-mentioned dysregulation in the fear neurocircuitry that is purported to lead to the failure to extinguish the fear response over time[23-25] and possibly also to the overgeneralization of fear to non-threatening cues.[26,27] Hypoactivity of the vmPFC and the hippocampus may contribute to the re-experiencing symptoms via difficulties in extinction learning, this process is actually further reinforced by avoidance.[28] These findings suggest that hippocampal volume is a factor in one’s vulnerability for PTSD, that is likely epigenetically shaped.[29] PE responders and controls had greater baseline hippocampal volume compared to treatment non-responders[30], indicating that larger hippocampal volume may correlate with risk for PTSD development[31,32] but also be related to better outcome in PE.

Prolonged Exposure promotes emotional processing through deliberate systematic confrontations with trauma-related stimuli using three key components of this CBT[33]:

repeated imaginal exposure (IE), which requires the individual to revisit their trauma memory in a therapeutic context;
in-vivo exposure (IVE) to places and situations that are avoided because they evoke stress and anxiety; and
emotional processing that focuses on reviewing the experience of exposure and its impact on thoughts related to the trauma.

Research has shown that during processing of threatening stimuli, individuals with PTSD demonstrated increased vmPFC (particularly rostral ACC) activation and decreased amygdala activation from pre- to post-treatment.[34] Further, studies found PE affects extinction: during fear extinction recall paradigm, individuals who underwent PE therapy demonstrated a decrease in rostral ACC activation from pre- to post-treatment[35]

Understanding the neurobiological processes involved with trauma can be used to optimize PTSD interventions, driving better retention through more personalized, more efficient, and more effective care.[36] Dropout rates are approximately 30% or more[37,38], which is not surprising, given that PTSD is characterized by behavioral avoidance. By identifying those with neurobiological biomarkers who may be at higher risk of dropping out of treatment, the administration of intranasal oxytocin is likely to increase retention rates in this cohort.[39]

Overall and Relative Effectiveness

Prolonged Exposure is one of the most researched interventions for PTSD. It has been studied in over 20 randomized clinical trials (RCTs) with more in progress. Data suggest that PE produces large treatment effects in regard to PTSD symptom reduction and subsequent loss of diagnosis.[40]

A 2019 published meta-analysis of 12 randomized clinical trials, comprising 922 participants, demonstrated that long-term benefits of psychotherapeutic and combined treatments were both superior to pharmacological treatments, alone, as first-line treatment for posttraumatic stress disorder. Based on intent to treat analyses, on average, 53% of those who initiate PE no longer meet diagnostic criteria for the disorder, and the rate of diagnostic change increases to 68% among individuals who complete treatment.[41]

The first randomized clinical trial on PE was conducted by Dr. Edna Foa and colleagues at the University of Pennsylvania (1991); they examined the efficacy of PE compared to Stress Inoculation Training (SIT), supportive counseling (SC), and waitlist control (WL) among female survivors of sexual assault.[42] While decreased PTSD symptoms were present for all groups posttreatment, at the three-month follow-up, the greatest reduction in PTSD symptoms was noted in the PE group. Resick and colleagues (2002) and Rothbaum, Astin, & Marsteller (2005) have also found PE to be superior to waitlist and equivalent to other trauma focused treatments in samples of female survivors of sexual assault.[43,44] On average, 53% of those who initiate PE therapy no longer meet diagnostic criteria for the disorder, and the rate of diagnostic change increases to 68% among individuals who complete treatment.[45] Similarly, long-term follow-up data supports the efficacy of PE with 83% of patients who received PE no longer meeting diagnostic criteria six years following their initial treatment.[46]

A review by the Agency for Healthcare Research and Quality[47], which used extensive criteria for evaluating study quality, included 19 RCTs of PE. The review concluded that there is high strength of evidence to support the efficacy of Prolonged Exposure therapy to reduce PTSD symptoms, depression symptoms, and the loss of PTSD diagnosis – concluding that and that trauma focused therapies, such as PE, are the most effective treatments for PTSD.[48]

Research with Military Personnel and Veterans

Prolonged Exposure therapy has been found to be effective at combating PTSD in active military as well as in Veterans. Schnurr and colleagues (2007) conducted the first RCT in female Veterans and demonstrated PE to be more efficacious than Present-Centered Therapy.[49] At follow-up, individuals who completed PE demonstrated a greater reduction of PTSD symptoms and were 1.8 times more likely to no longer meet diagnostic criteria for PTSD. Another RCT compared therapeutic modalities of post-9/11 Veterans: sertraline plus enhanced medication management, PE plus placebo, and PE plus sertraline.[50] Results of this trial revealed significant reductions in PTSD symptom severity in both PE plus placebo and PE plus sertraline. Additional RCTs demonstrated effectiveness for reducing PTSD symptoms in U.S. military personnel[51], U.S. Veterans[52-54] and Israeli Veterans.[55]

Research with Comorbidities and Special Populations

PE has also been found to be effective for reducing PTSD symptoms when comorbidities are present. As noted in a meta-analytic review by Powers and colleagues (2010), PE is effective at reducing depression symptoms.[56] Regarding substance use disorder, research shows that PE integrated with, or offered concurrently with substance use treatment, is more effective for reducing PTSD symptoms than substance use only treatment.[57-59] Additionally, PE has been effective in ameliorating trauma-related guilt[60], other non-fear emotions such as anger and shame[61] and improves regulation of emotion.[62,63]

Emerging Issues

Since extensive research has established that PE is effective for treating PTSD, newer studies are targeting ways to make PE more accessible and even more effective. One RCT demonstrated that massed PE (10 sessions over a two-week period) is not only well tolerated, but actually yield low dropout rates.[64] Another novel RCT demonstrated that Prolonged Exposure for Primary Care which included four, 30-min appointments delivered over 4 to 6 weeks produced a large reduction in PTSD severity compared to a minimal-contact control group.[65] Such endeavors promise to increase patient access to effective intervention and retention in care.

Session Content

PE is a manualized exposure-based psychological intervention designed to treat PTSD. This therapy is typically delivered in 8 to 15, 90-minute sessions, usually on a weekly basis. PE promotes emotional processing of the trauma memory through a deliberate systematic approach utilizing trauma-related stimuli.[66] The four key components of PE are:

Psychoeducation about treatment, common reactions to trauma, and breathing retraining.
Imaginal exposure, which requires repeatedly retelling the trauma memory out loud (in present tense, with eyes closed) after-which the client would listen to an audio recording of the session prior to the next treatment session.
In-vivo/direct exposure to places, things, and situations that are avoided because they evoke distress and anxiety.
Emotional processing that focuses on reviewing the experience of exposure and its impact on thoughts related to the self, the world, and the trauma.

Prolonged Exposure is typically provided over a period of about three months with weekly individual sessions, resulting in eight to 15 sessions overall. In order for the individual to engage in exposure and sufficiently process the experience, 60 to 120-minute sessions are usually needed.

Therapists begin with an overview of treatment and seek to understand the patient’s past experiences. Psychoeducation continues and the patient learns a breathing technique to manage anxiety. Exposure generally begins after the assessment and initial session. As PE is very anxiety-provoking for most patients, the therapist ensures patient-provider relationship is perceived to be a safe space. Both imaginal and in-vivo exposure are utilized at a pace dictated by the patient.

Imaginal exposure occurs in session with the patient describing their traumatic event in detail, as if they were currently immersed in the situation, with guidance from the therapist. The patient and therapist discuss and process the emotion(s) raised by the imaginal exposure. A recording of the patient describing the event is made, so that the patient can listen to the recording between sessions, further process the emotions and practice the therapeutic breathing techniques.
In-vivo exposure is the confrontation of feared stimuli outside of therapy, which is to be done as homework prior to the next session. The therapist and patient identify a range of possible stimuli and situations connected to the traumatic fear, such as specific places or people, and devise a plan to confront/be exposed to between sessions. The patient is encouraged to challenge themselves but to do so in steps to ensure success when confronting the feared stimuli while coping with the emotion(s) associated with it.[67]

The utilization of virtual reality (VR) is another option to be used in Prolonged Exposure therapy. VR consists of a fully-immersive, 3-D environment, transporting people to an engaging, interactive environment. VR exposure therapy (VRET) permits individualized, gradual, controlled, immersive exposure that is easy for therapists to implement and is often more acceptable to patients than in-vivo exposure as it is more controlled and feels safer. VRET has been used for the treatment of PTSD, as well as social anxiety and panic disorder.[68]

Obstacles to and Options of Exposure Therapy

Patient fears are one of the main barriers to exposure therapy. If therapy requires prolonged exposure to their most feared stimuli, patients may refuse or drop out of treatment.

A second barrier may arise with the difficulties that can occur in both imaginal exposure and in-vivo exposure. In imaginal exposure, therapists cannot know or control what the patient imagines and the ability to create vivid mental images declines with age.[69] In-vivo exposure is often difficult or impossible to arrange inside the office and usually impractical to do outside the office.[70]

Therapist concerns about exposure therapy are a third barrier. Therapists often worry that exposure will be distressing for both therapist and patient and will increase patient drop out.[71-75] When therapists have no way to control exposure, there is a risk that exposure may actually sensitize the patient and worsen their anxiety; VR ameliorates this risk. With VR, therapists can control different aspects of the patients’ experience during exposure, permitting gradual, repeatable, individualized exposure. By minimizing the risk of patient distress, the chance of patient success is maximized.

A fourth barrier to exposure therapy is that relatively few mental health providers are trained in this modality. While extensive research supports imaginal exposure as a primary line of therapy for PTSD, a broad survey found that the majority of the licensed psychologists in clinical practice were not using this evidence-based intervention.[76]

One way to negate some of the afore-mentioned barriers would be formal clinical training to lessen potential therapist misconceptions of exposure treatment. Deacon et al.[77] reported that therapists who attended a day-long didactic workshop about exposure therapy showed a decrease in negative beliefs about the treatment approach and an increase in using it. Even therapists trained and interested in exposure, such as imaginal exposure for PTSD, still underutilize the treatment. Research has shown that directly addressing clinicians’ concerns increases adoption and utilization of this therapy as does training that incorporates motivational enhancement and/or offers a supportive learning community.[78,79] Further, therapists with doctorate-level training report fewer reservations about exposure therapy compared to other mental health professionals, perhaps as a result of having more training opportunities.[80]

A final obstacle to offering exposure therapy may be time and/or difficulty involved, especially for in-vivo exposure. In-vivo exposure may be: prohibited by a clinic’s policy, difficult to arrange, take too long, and present confidentiality risks. Despite its effectiveness, these factors limit the availability of exposure therapy.[81] VR technology, however, can help overcome these obstacles and support patient access to and acceptance of exposure therapy.

Clinically, VRET is a practical, empirically-based treatment that makes exposure therapy easier and more acceptable for therapists and patients. This modality can help patients learn and practice anxiety management skills, while permitting controlled, gradual exposure; this minimizes distress while optimizing treatment success. Over two decades of research demonstrate the efficacy of VRET for anxiety disorders, particularly phobias. Meta-analyses demonstrate a large effect size compared to a control or waitlist condition, with no significant difference in effect size or attrition rates when compared to in-vivo exposure therapy.[82-86]

VRET overcomes the four prior-mentioned limitations of imaginal exposure. This modality allows the therapist to see what the patient sees within the virtual environment. Not only can the therapist choose the VR content, but they can personalize it specifically for their patient’s needs. Further, as the therapist guides their patient through exposure while in the office, patients report feeling engaged and safe in a “real” environment – much more so than if they were to practice facing a feared stimuli on their own, in a real-world setting.[87,88] As therapists monitor and guide patients to look at specific content during the VR session, they can manage any anxiety that arises, improving the efficiency of the treatment, ultimately improving patient outcomes.[89] Additionally, VR can be utilized in psychotherapy beyond exposure; immersion in relaxing virtual environments can help patients learn and practice anxiety management skills, increasing overall treatment efficacy.

VRET, however, does have limitations. Virtual environments are currently not available for all anxiogenic stimuli. Cybersickness can also limit VR’s use with some patients.[90] Despite these limitations, accessibility to VR has increased, as it has become increasingly affordable; the cost of VR software and hardware continues to decline, while the quantity and quality of VR content increases.[91]

If you are suffering from PTSD and are interested in finding out if Prolonged Exposure therapy would help alleviate your symptoms, please reach out to a therapist to schedule an appointment.

Contributed by: Jennifer (Ghahari) Smith, Ph.D..

REFERENCES

1 “PTSD: National Center for PTSD,” U.S. Department of Veterans Affairs. (accessed 7/3/2020) www.ptsd.va.gov/professional/treat/txessentials/prolonged_exposure_pro.asp

2 “Clinical Practice Guideline for the Treatment of Posttraumatic Stress Disorder: Prolonged Exposure (PE),” American Psychological Association. (accessed 7/3/20) www.apa.org/ptsd-guideline/treatments/prolonged-exposure

3 “Center for the Treatment and Study of Anxiety: About Prolonged Exposure Therapy,” Perelman School of Medicine – University of Pennsylvania: Penn Psychiatry. (accessed 7/2/20) www.med.upenn.edu/ctsa/workshops_pet.html

4 Ibid.

5 “PTSD: National Center for PTSD”

6 Rauch S., Liberzon I. (2016). “Mechanisms of action in psychotherapy,” in The Biological Basis of Posttraumatic Stress Disorder: From Brain to Mind, eds Liberzon I., Ressler K. (New York, NY: Oxford University Press; ), 353–372.

7 “PTSD: National Center for PTSD”

8 Rauch S., Liberzon I. (2016).

9 Sripada R. K., Rauch S. A. M. (2015). Between-session and within-session habituation in prolonged exposure therapy for posttraumatic stress disorder: a hierarchical linear modeling approach. J. Anxiety Disord. 30, 81–87. 10.1016/j.janxdis.2015.01.002

10 Maren S., Phan K. L., Liberzon I. (2013). The contextual brain: implications for fear conditioning, extinction and psychopathology. Nat. Rev. Neurosci. 14, 417–428. 10.1038/nrn3492

11 Rothbaum B. O., Astin M. C., Marsteller F. (2005). Prolonged exposure versus eye movement desensitization and reprocessing (EMDR) for PTSD rape victims. J. Trauma. Stress 18, 607–616. 10.1002/jts.20069

12 Rauch S., Liberzon I. (2016). “Mechanisms of action in psychotherapy,” in The Biological Basis of Posttraumatic Stress Disorder: From Brain to Mind, eds Liberzon I., Ressler K. (New York, NY: Oxford University Press; ), 353–372.

13 Shin L. M., Liberzon I. (2010). The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology 35, 169–191. 10.1038/npp.2009.83

14 Rauch S. L., Shin L. M., Phelps E. A. (2006). Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research—past, present and future. Biol. Psychiatry 60, 376–382. 10.1016/j.biopsych.2006.06.004

15 Shin L. M., Rauch S. L., Pitman R. K. (2006). Amygdala, medial prefrontal cortex and hippocampal function in PTSD. In. Ann. N Y Acad. Sci. 1071, 67–79. 10.1196/annals.1364.007

16 Milad M. R., Pitman R. K., Ellis C. B., Gold A. L., Shin L. M., Lasko N. B., et al. . (2009). Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol. Psychiatry 66, 1075–1082. 10.1016/j.biopsych.2009.06.026

17 Quirk G. J., Russo G. K., Barron J. L., Lebron K. (2000). The role of ventromedial prefrontal cortex in the recovery of extinguished fear. J. Neurosci. 20, 6225–6231. 10.1523/jneurosci.20-16-06225.2000

18 Rauch S. L., Shin L. M., Phelps E. A. (2006).

19 Shin L. M., Rauch S. L., Pitman R. K. (2006).

20 Liberzon I., Abelson J. L. (2016). Context processing and the neurobiology of post-traumatic stress disorder. Neuron 92, 14–30. 10.1016/j.neuron.2016.09.039

21 Hayes J. P., Hayes S. M., Mikedis A. M. (2012). Quantitative meta-analysis of neural activity in posttraumatic stress disorder. Biol. Mood Anxiety Disord. 2:9. 10.1186/2045-5380-2-9

22 Koch S. B. J., van Zuiden M., Nawijn L., Frijling J. L., Veltman D. J., Olff M. (2016). Aberrant resting-state brain activity in posttraumatic stress disorder: a meta-analysis and systematic review. Depress. Anxiety 33, 592–605. 10.1002/da.22478

23 Rauch S. L., Shin L. M., Phelps E. A. (2006).

24 Jovanovic T., Ressler K. J. (2010). How the neurocircuitry and genetics of fear inhibition may inform our understanding of PTSD. Am. J. Psychiatry 167, 648–662. 10.1176/appi.ajp.2009.09071074

25 Liberzon I., Abelson J. L. (2016).

26 Stevens J. S., Jovanovic T., Fani N., Ely T. D., Glover E. M., Bradley B., et al. . (2013). Disrupted amygdala-prefrontal functional connectivity in civilian women with posttraumatic stress disorder. J. Psychiatr. Res. 47, 1469–1478. 10.1016/j.jpsychires.2013.05.031

27 Lopresto D., Schipper P., Homberg J. R. (2016). Neural circuits and mechanisms involved in fear generalization: implications for the pathophysiology and treatment of posttraumatic stress disorder. Neurosci. Biobehav. Rev. 60, 31–42. 10.1016/j.neubiorev.2015.10.009

28 Pitman R. K., Rasmusson A. M., Koenen K. C., Shin L. M., Orr S. P., Gilbertson M. W., et al. . (2012). Biological studies of post-traumatic stress disorder. Nat. Rev. Neurosci. 13, 769–787. 10.1038/nrn3339

29. Stojek M. M., McSweeney L. B., Rauch, S.A. (2018). Neuroscience Informed Prolonged Exposure Practice: Increasing Efficiency and Efficacy Through Mechanisms. Frontiers in Behavioral Neuroscience. 12:281. 10.3389/fnbeh.2018.00281

30 Rubin M., Shvil E., Papini S., Chhetry B. T., Helpman L., Markowitz J. C., et al. . (2016). Greater hippocampal volume is associated with PTSD treatment response. Psychiatry Res. Neuroimaging 252, 36–39. 10.1016/j.pscychresns.2016.05.001

31 Gilbertson M. W., Shenton M. E., Ciszewski A., Kasai K., Lasko N. B., Orr S. P., et al. . (2002). Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat. Neurosci. 5, 1242–1247. 10.1038/nn958

32 Lindgren L., Bergdahl J., Nyberg L. (2016). Longitudinal evidence for smaller hippocampus volume as a vulnerability factor for perceived stress. Cereb. Cortex 26, 3527–3533. 10.1093/cercor/bhw154

33 Foa E. B. (2011). Prolonged exposure therapy: past, present and future. Depress. Anxiety 28, 1043–1047. 10.1002/da.20907

34 Felmingham K., Kemp A., Williams L., Das P., Hughes G., Peduto A., et al. . (2007). Changes in anterior cingulate and amygdala after cognitive behavior therapy of posttraumatic stress disorder. Psychol. Sci. 18, 127–129. 10.1111/j.1467-9280.2007.01860.x\

35 Helpman L., Marin M.-F., Papini S., Zhu X., Sullivan G. M., Schneier F., et al. . (2016a). Neural changes in extinction recall following prolonged exposure treatment for PTSD: a longitudinal fMRI study. Neuroimage Clin. 12, 715–723. 10.1016/j.nicl.2016.10.007

36 Tuerk P. W. (2014). Starting from something: augmenting exposure therapy and methods of inquiry. Am. J. Psychiatry 171, 1034–1037. 10.1176/appi.ajp.2014.14070880

37 Bradley R., Greene J., Russ E., Dutra L., Westen D. (2005). A multidimensional meta-analysis of psychotherapy for PTSD. Am. J. Psychiatry 162, 214–227. 10.1176/appi.ajp.162.2.214

38 Eftekhari A., Ruzek J. I., Crowley J. J., Rosen C. S., Greenbaum M. A., Karlin B. E. (2013). Effectiveness of national implementation of prolonged exposure therapy in veterans affairs care. JAMA Psychiatry 70, 949–955. 10.1001/jamapsychiatry.2013.36

39 Stojek M. M., McSweeney L. B., Rauch, S.A. (2018).

40 “PTSD: National Center for PTSD”

41 Bradley R., Greene J., Russ E., Dutra L., Westen D. (2005).

42 Foa, E. B., Rothbaum, B. O., Riggs, D. S., & Murdock, T. B. (1991). Treatment of posttraumatic stress disorder in rape victims: A comparison between cognitive-behavioral procedures and counseling. Journal of Consulting and Clinical Psychology, 59, 715-723. doi:10.1037//0022-006x.59.5.715

43 Resick, P. A., Nishith, P., Weaver, T. L., Astin, M. C., & Feuer, C. A. (2002). A comparison of cognitive-processing therapy with prolonged exposure and a waiting condition for the treatment of chronic posttraumatic stress disorder in female rape victims. Journal of Consulting and Clinical Psychology, 70, 867-879. doi:10.1037//0022-006x.70.4.867

44 Rothbaum, B. O., Astin, M. C., & Marsteller, F. (2005). Prolonged exposure versus eye movement desensitization and reprocessing (EMDR) for PTSD rape victims. Journal of Traumatic Stress, 18, 607-616. doi:10.1002/jts.20069

45 Bradley, R., Greene, J., Russ, E., Dutra, L., & Westen, D. (2005). A multidimensional meta-analysis of psychotherapy for PTSD. American Journal of Psychiatry, 162, 214-227. doi:10.1176/appi.ajp.162.2.214

46 Resick, P. A., Williams, L. F., Suvak, M. K., Monson, C. M., & Gradus, J. L. (2012). Long-term outcomes of cognitive-behavioral treatments for posttraumatic stress disorder among female rape survivors. Journal of Consulting and Clinical Psychology, 80, 201-210. doi:10.1037/a0026602

47 Forman-Hoffman, V., Middleton, J. C., Feltner, C., Gaynes B. N., Weber, R.P., Bann, C., ... Green, J. (2018) Psychological and pharmacological treatments for adults with posttraumatic stress disorder: A systematic review update. Comparative Effectiveness Review, No. 207. (Prepared by the RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center under Contract No. 290-2015-00011-I for AHRQ and PCORI.) AHRQ Publication No. 18-EHC011-EF. PCORI Publication No. 2018-SR-01. Rockville, MD: Agency for Healthcare Research and Quality; May 2018. Retrieved from: www.effectivehealthcare.ahrq.gov/reports/final.cfm doi:10.23970/AHRQEPCCER207

48 Bradley R., Greene J., Russ E., Dutra L., Westen D. (2005).

49 Schnurr, P. P., Friedman, M. J., Engel, C. C., Foa, E. B., Shea, M. T., Chow, B. K., ... Turner, C. (2007). Cognitive behavioral therapy for posttraumatic stress disorder in women: A randomized controlled trial. JAMA, 297, 820-830. doi:10.1001/jama.297.8.820

50 Rauch, S. A., Kim, H. M., Powell, C., Tuerk, P. W., Simon, N. M., Acierno, R., ... Peterson, A. L. (2018). Efficacy of prolonged exposure therapy, sertraline hydrochloride, and their combination among combat Veterans with posttraumatic stress disorder: A randomized clinical trial. JAMA Psychiatry. Advance online publication. doi:10.1001/jamapsychiatry.2018.3412

51 Foa, E. B., McLean, C. P., Zang, Y., Rosenfield, D., Yadin, E., Yarvis, J. S., ... Fina, B. A. (2018). Effect of prolonged exposure therapy delivered over 2 weeks vs 8 weeks vs present-centered therapy on PTSD symptom severity in military personnel: A randomized clinical trial. JAMA, 319, 354-364. doi:10.1001/jama.2017.21242

52 Rauch, S. A., Kim, H. M., Powell, C., Tuerk, P. W., Simon, N. M., Acierno, R., ... Peterson, A. L. (2018).

53 Ford, J. D., Grasso, D. J., Greene, C. A., Slivinsky, M., & DeViva, J. C. (2018). Randomized clinical trial pilot study of prolonged exposure versus present centered affect regulation therapy for PTSD and anger problems with male military combat Veterans. Clinical Psychology & Psychotherapy, 25, 641-649. doi:10.1002/cpp.2194

54 Rauch, S. A., King, A. P., Abelson, J., Tuerk, P. W., Smith, E., Rothbaum, B. O., ... Liberzon, I. (2015). Biological and symptom changes in posttraumatic stress disorder treatment: A randomized clinical trial. Depression and Anxiety, 32, 204-212. doi:10.1002/da.22331

55 Nacasch, N., Foa, E. B., Huppert, J. D., Tzur, D., Fostick, L., Dinstein, Y., ... Zohar, J. (2011). Prolonged exposure therapy for combat-and terror-related posttraumatic stress disorder: A randomized control comparison with treatment as usual. Journal of Clinical Psychiatry, 72, 1174-1180. doi:10.4088/jcp.09m05682blu

56 Powers, M. B., Halpern, J. M., Ferenschak, M. P., Gillihan, S. J., & Foa, E. B. (2010). A meta-analytic review of prolonged exposure for posttraumatic stress disorder. Clinical Psychology Review, 30, 635-641. doi:10.1016/j.cpr.2010.04.007

57 Back, S. E., Foa, E. B., Killeen, T. K., Teesson, M., Mills, K. L., Cotton, B. D., & Carroll, K. M. (2014). Concurrent treatment of PTSD and substance use disorders using prolonged exposure (COPE): Therapist guide. Oxford University Press, USA.

58 Roberts, N. P., Roberts, P. A., Jones, N., & Bisson, J. I. (2015). Psychological interventions for post-traumatic stress disorder and comorbid substance use disorder: A systematic review and meta-analysis. Clinical Psychology Review, 38, 25-38. doi:10.1016/j.cpr.2015.02.007

59 Ruglass, L. M., Shevorykin, A., Radoncic, V., Smith, K. M., Smith, P. H., Galatzer-Levy, I. R., ... Hien, D. A. (2017). Impact of cannabis use on treatment outcomes among adults receiving cognitive-behavioral treatment for PTSD and substance use disorders. Journal of Clinical Medicine, 6, 14. doi:10.3390/jcm6020014

60 Resick, P. A., Williams, L. F., Suvak, M. K., Monson, C. M., & Gradus, J. L. (2012).

61 Langkaas, T. F., Hoffart, A., Ã˜ktedalen, T., Ulvenes, P. G., Hembree, E. A., & Smucker, M. (2017). Exposure and non-fear emotions: A randomized controlled study of exposure-based and rescripting-based imagery in PTSD treatment. Behaviour Research and Therapy, 97, 33-42. doi:10.1016/j.brat.2017.06.007

62 Jerud, A. B., Pruitt, L. D., Zoellner, L. A., & Feeny, N. C. (2016). The effects of prolonged exposure and sertraline on emotion regulation in individuals with posttraumatic stress disorder. Behaviour Research and Therapy, 77, 62-67. doi:10.1016/j.brat.2015.12.002

63 Jerud, A. B., Zoellner, L. A., Pruitt, L. D., & Feeny, N. C. (2014). Changes in emotion regulation in adults with and without a history of childhood abuse following posttraumatic stress disorder treatment. Journal of Consulting and Clinical Psychology, 82, 721-730. doi:10.1037/a0036520

64 Foa, E. B., McLean, C. P., Zang, Y., Rosenfield, D., Yadin, E., Yarvis, J. S., ... Fina, B. A. (2018).

65 Cigrang, J.A., & Peterson, A.L. (2017). Stepped-care approaches to posttraumatic stress disorder: Sharpening tools for the clinician's toolbox. Pragmatic Case Studies in Psychotherapy, 13, 142-153. doi:10.14713/pcsp.v13i2.2004

66 “Clinical Practice Guideline for the Treatment of Posttraumatic Stress Disorder: Prolonged Exposure (PE)”

67 Ibid.

68 Stojek M. M., McSweeney L. B., Rauch, S.A. (2018).

69 Grenier S, Forget H, Bouchard S, Isere S, Belleville S, Potvin O, et al. Using virtual reality to improve the efficacy of cognitive-behavioral therapy (CBT) in the treatment of late-life anxiety: Preliminary recommendations for future research. Int Psychogeriatr (2015) 27(7):1217–25. 10.1017/S1041610214002300

70 Deacon BJ, Farrell NR, Kemp JJ, Dixon LJ, Sy JT, Zhang AR, et al. Assessing therapist reservations about exposure therapy for anxiety disorders: the Therapist Beliefs about Exposure Scale. J Anxiety Disord (2013. a) 27(8):772–80. 10.1016/j.janxdis.2013.04.006

71 Hembree EA, Rauch SAM, Foa EB. Beyond the manual: The insider’s guide to Prolonged Exposure therapy for PTSD. Cognit Behav Pract (2003) 10(1):22–30. 10.1016/S1077-7229(03)80005-6

72 Deacon BJ, Farrell NR. Therapist Barriers to the Dissemination of Exposure Therapy. In: Deacon BJ, editor. Handbook of Treating Variants and Complications in Anxiety Disorders. Department of Psychology, University of Wyoming; (2013). 10.1007/978-1-4614-6458-7_23

73 Gunter RW, Whittal ML. Dissemination of cognitive-behavioral treatments for anxiety disorders: Overcoming barriers and improving patient access. Clin Psychol Rev (2010) 30(2):194–202. 10.1016/j.cpr.2009.11.001

74 Harned MS, Dimeff LA, Woodcock EA, Contreras I. Predicting adoption of exposure therapy in a randomized controlled dissemination trial. J Anxiety Disord (2013) 27(8):754–62. 10.1016/j.janxdis.2013.02.006

75 Pittig A, Kotter R, Hoyer J. The struggle of behavioral therapists with exposure: self-reported practicability, negative beliefs, and therapist distress about exposure-based interventions. Behav Ther (2019) 50(2):353–66. 10.1016/j.beth.2018.07.003

76 Becker CB, Zayfert C, Anderson E. A survey of psychologists’ attitudes towards and utilization of exposure therapy for PTSD. Behav Res Ther (2004) 42(3):277–92. 10.1016/S0005-7967(03)00138-4

77 Deacon BJ, Farrell NR. (2013)

78 Becker CB, Zayfert C, Anderson E. (2004)

79 Pittig A, Kotter R, Hoyer J. (2019)

80 Deacon BJ, Farrell NR. (2013)

81 Pittig A, Kotter R, Hoyer J. (2019)

82 Carl E, Stein AT, Levihn-Coon A, Pogue JR, Rothbaum B, Emmelkamp P, et al. Virtual reality exposure therapy for anxiety and related disorders: A meta-analysis of randomized controlled trials. J Anxiety Disord (2019) 61(August 2018):27–36. 10.1016/j.janxdis.2018.08.003

83 Parsons TD, Rizzo AA. Affective outcomes of virtual reality exposure therapy for anxiety and specific phobias: A meta-analysis. J Behav Ther Exp Psychiatry (2008) 39(3):250–61. 10.1016/j.jbtep.2007.07.007

84 Benbow AA, Anderson PL. A meta-analytic examination of attrition in virtual reality exposure therapy for anxiety disorders. J Anxiety Disord (2019) 61:18–26. 10.1016/j.janxdis.2018.06.006

85 Fodor LA, Coteţ CD, Cuijpers P, Szamoskozi Ș, David D, Cristea IA. The effectiveness of virtual reality based interventions for symptoms of anxiety and depression: A meta-analysis. Sci Rep (2018) 8(1):10323. 10.1038/s41598-018-28113-6

86 Opriş D, Pintea S, García-Palacios A, Botella C, Szamosközi Ș, David D. Virtual reality exposure therapy in anxiety disorders: a quantitative meta-analysis. Depression Anxiety (2012) 29(2):85–93. 10.1002/da.20910

87 Freeman D, Reeve S, Robinson A, Ehlers A, Clark D, Spanlang B, et al. Virtual reality in the assessment, understanding, and treatment of mental health disorders. Psychol Med (2017) 47(14):2393–400. 10.1017/S003329171700040X

88 Riva G. Virtual reality in psychotherapy: review. CyberPsychol Behav (2005) 8(3):220–30. 10.1089/cpb.2005.8.220

89 Goncalves R, Pedrozo AL, Coutinho ESF, Figueira I, Ventura P. Efficacy of virtual reality exposure therapy in the treatment of PTSD: a systematic review. PLoS One (2012) 7(12):e48469. 10.1371/journal.pone.0048469

90 Weech S, Kenny S, Barnett-Cowan M. Presence and cybersickness in virtual reality are negatively related: a review. Front Psychol (2019) 10(FEB):1–19. 10.3389/fpsyg.2019.00158

91 Boeldt D, McMahon E, McFaul M, Greenleaf, W. Using Virtual Reality Exposure Therapy to Enhance Treatment of Anxiety Disorders: Identifying Areas of Clinical Adoption and Potential Obstacles. Front Psychol (2019) 10:773 doi: 10.3389/fpsyt.2019.00773