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Virtual reality in anxiety disorders: the past and the future Expert Rev. Neurotherapeutics 8(2), xxx–xxx (2008)

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Author for correspondence Applied Technology for Neuro-Psychology Lab, Istituto Auxologico Italiano, Via Pelizza da Volpedo, 41. 20149 Milan, Italy Tel.: +39 02 61911 2726 Fax: +39 02 61911 2892 [email protected]

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One of the most effective treatments of anxiety is exposure therapy: a person is exposed to specific feared situations or objects that trigger anxiety. This exposure process may be done through actual exposure, with visualization, by imagination or using virtual reality (VR), that provides users with computer simulated environments with and within which they can interact. VR is made possible by the capability of computers to synthesize a 3D graphical environment from numerical data. Furthermore, because input devices sense the subject’s reactions and motions, the computer can modify the synthetic environment accordingly, creating the illusion of interacting with, and thus being immersed within the environment. Starting from 1995, different experimental studies have been conducted in order to investigate the effect of VR exposure in the treatment of subclinical fears and anxiety disorders. This review will discuss their outcome and provide guidelines for the use of VR exposure for the treatment of anxious patients.

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Alessandra Gorini† and Giuseppe Riva

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KEYWORDS: anxiety disorders • presence • specific phobia • virtual reality • virtual reality exposure therapy

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A large number of people around the world suffer from anxiety disorders [1] that prevent them from doing a variety of daily-life activities such as driving, taking a plane, interacting with someone unknown or staying in crowded places. In a large proportion of anxious individuals, these commodities provoke feelings of being strangled and of imminent death so acute that they become unable to conduct a normal life. Even if these disorders tend to worsen with time and lack of clinical interventions, patients usually tend to refuse treatment because they are too frightened to go through it. In fact, even if many different kinds of treatment are available for anxiety disorders, such as behavioral treatments (relaxation, exposure, modelling and roleplay), cognitive therapies (thought stopping, mental distraction and thought recording), medication, psychodynamic therapy, family therapy and biofeedback, many studies have demonstrated that the exposure-based treatments are among the most effective [2–4]. Despite its effectiveness, exposure-based therapy presents important limitations:

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• Many patients are reticent to expose themselves to the real phobic stimulus or situation • In vivo exposure can never be fully controlled by the therapist and its intensity can be too strong for the patient • This technique often requires that therapists accompany patients into anxiety-provoking situations in the real world at great cost to the patient, and with great time expenditure on the part of both therapist and patient. These are the main reasons for which from the mid to late 1990s some therapists around the world have started to add the virtual reality (VR) to the in vivo exposure-based therapy, providing in-office, controlled exposure therapy to anxious patients, mitigating many of the complications of the in vivo exposure. In 2000, the increasing success of VR in the treatment of anxiety disorders was documented by a survey performed between a panel of 62 experts in psychotherapy who affirmed that only 18 of the 38 analyzed therapeutic interventions were predicted to increase in the following 10 years. VR use was ranked third and fifth [5].

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• The graphic rendering system that generates, at 20–30 frames per second, the VE • The output tools (visual, aural and haptic) that immerse the user in the VE As we have just seen, VR is usually described as a particular collection of technological hardware and software. However, it is also possible to describe it in terms of human experience, using the concept of presence [8,9]: VR is the medium able to induce the experience of “presence” in a computer-generated world. Presence is usually defined as the “sense of being there” [9], or as the “feeling of being in a world that exists outside the self ” [10]. Different studies showed a direct connection between the intensity of the emotions experienced in VR and the level of presence elicited by it [11]. The first commercial version of a VR system was developed by Morton Heilig in 1956 [12], but the possibility to have a personalized virtual experience came only in 1968 when Ivan Sutherland developed the first head-mounted display (HMD) that allowed the user to view 3D wire frame objects. In the early 1980s, the first program that allowed people to interact and change computer generated images through bodily movements was created by Krueger [13], who was one of the first to suggest a possible role for VR in the treatment of mental health disorders [14]. VR systems became available for the consumer market between 1985 and 1990 when several video games companies started to sell quite inexpensive HMD and data gloves used to interact with the virtual words. Actually, even small laboratories or private users (i.e., private clinicians) have the possibility to buy a VR system that guarantees a good quality of immersion, since the cost varies from approximately US$5000–10000 (the recent PCs or laptops are usually powerful enough to handle complex 3D simulations).

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Since the early 1980s, when computer scientists and the media used the term for the first time, VR has been usually described as a computer-simulated environment with and within which people can interact. VR is made possible by the capability of computers for synthesizing a 3D graphical environment from numerical data. Furthermore, because input devices sense the subject’s reactions and motions, the computer can modify the synthetic environment accordingly, creating the illusion of interacting with, and thus being immersed within the environment. Using visual, aural or haptic devices, the subject experiences the graphical environment as if it were real. These computergenerated scenarios may represent either a model of a realworld object, such as a house, or an abstract world that does not exist in a real sense but is understood by humans as real. A VR system is the combination of the hardware and software that enables the development of virtual environments (VEs). The hardware components receive input from usercontrolled devices and convey multisensory outputs to create the illusion of a virtual world. The software component manages the hardware that makes up the VR system. Separate VR applications are then responsible for the creation of specific virtual worlds. Typically, a VR system is composed of (FIGURE 1) [6,7]:

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Virtual reality: from technology to presence

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• The database construction and virtual object modeling software for building and maintaining detailed and realistic models of the virtual world. In particular, the software handles the geometry, texture, intelligent behavior, and physical modeling of hardness, inertia and surface plasticity of any object included in the virtual world

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• The input tools (trackers, gloves or mice) that continually reports the position and movements of the users

Figure 1. Typical virtual reality setting.

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Virtual reality in healthcare

Thanks to its commercial diffusion and to the decreasing cost of technology, starting from the 1990s the use of VR in medicine has become more widespread [15]. The growing interest in medical applications of VR is also highlighted by the increasing number of scientific articles published each year on this topic: searching Medline with the keyword “virtual reality”, the total number of publications has increased from 45 in 1995 to 289 in 2006, showing an average annual growth rate of nearly 14%. For many healthcare professionals, VR is first of all considered a technology. However, the analysis of the different VR applications clearly shows that the focus on technological devices is not the same in all areas of medicine and it is related to the specific goals of the healthcare provider. For instance, Rubino et al. [16], McCloy and Stone [17], and Székely and Satava [18] in their reviews describe VR as: “a collection of technologies that allow people to interact efficiently with 3D computerized databases in real time using their natural senses and skills” [17]. This definition lacks any reference to

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Virtual reality in anxiety disorders

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practice (habituation). Because many people find it hard to face their fears, traditional exposure therapy typically starts with exposing a person to situations that create only mild-to-moderate symptoms of anxiety and gradually progresses to situations that create severe anxiety. With repeated exposure, feared situations begin to elicit less and less fear and anxiety for the person, and he or she feels less of an urge to avoid them. In the last few years, researches and clinicians have started to use VR to carry out a specific form of exposure treatment (VR exposure therapy [VRET]). VRET has the potential to control, enhance and accelerate the treatment process offering several advantages over real exposure or imagination techniques. Compared with the in vivo exposure, VRET is completely controlled: the quality, intensity and frequency of the exposure is entirely decided by the therapist in his/her office and can be stopped any time the patient is unable to tolerate it. The flexibility of VEs also allows the patient to overpractice in situations often much worse and more exaggerated than those that are likely to be encountered in real life. This allows patients to develop a sense of mastery and the confidence to carry out the task successfully. In addition, the patient can be exposed repeatedly only to the specific feared stimuli. A typical example of this point regards the patients who only have fear of airplane landings and is clearly explained by Wiederhold [23]. Using the VRET, during a single 1-h session such a patient can practice several landings without wasting time with all other aspects of air travel. Moreover, since the exposure takes place in a safe and controlled environment (the therapist’s office), the therapist can monitor the patient’s reactions with different instruments (e.g., psychological questionnaire and biomonitoring systems) and follow the symptom reduction. Compared with imaginal exposure, VRET has the advantage to be highly immersive and more realistic since it has the potential to stimulate different sensory modalities through visual, auditory and sometimes tactile cues, motion and vibration that help patients to feel immersed in the experience. The feeling of presence that patients experience in these environments, involving all the sensorimotor channels, enables them to really “live” the experience in a more vivid and realistic manner than they could do through their own imagination [24]. This should translate into fewer treatment sessions, and, therefore, less cost for treatment [25,26]. In addition, during virtual exposure, the therapist can see what the patient sees, identifying the exact stimuli that are causing anxiety in patients. In summary, the flexibility of VE allows the therapist to tailor sessions to meet the needs of each client, offering the following advantages: interactivity, flexibility, controllability, confidentiality, safety, timesaving, cost savings and repeatability. This is why, used in combination with the traditional cognitive–behavioral therapy, VRET is a promising method of increasing the likelihood of therapeutic success, at least in the field of anxiety disorders and specific phobias.

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HMD and instrumented clothing such as gloves or suits. In fact, less than 20% of VR healthcare applications in medicine are actually using any immersive equipment. However, if we shift our attention on behavioral sciences, where immersive devices are used by more than 50% of the applications, VR is described as “an advanced form of humancomputer interface that allows the user to interact with and become immersed in a computer-generated environment in a naturalistic fashion” [19]. These two definitions underline two different focuses of VR in medicine: VR as a simulation tool and VR as an interaction tool. For physicians and surgeons, the simulation focus of VR prevails on the interaction one: their ultimate goal of VR is the presentation of virtual objects to all of the human senses in a way identical to their natural counterpart [18]. As noted by Satava and Jones [20], as more and more of the medical technologies become information-based, it will be possible to represent a patient with higher fidelity to a point that the image may become a surrogate for the patient – the medical avatar. In this sense, an effective VR system should offer realistic body parts or avatars that interact with external devices such as surgical instruments as near as possible to their real models. For clinical psychologists and psychiatrists the interaction focus of VR prevails on the simulation one: they use VR to provide a new human–computer interaction paradigm in which users are no longer simply external observers of images on a computer screen but are active participants within a computergenerated 3D virtual world [21,22]. Starting from 1990, different companies have developed complete VR systems for the treatment of common anxiety disorders and specific phobias, such as: fear of heights, fear of flying, driving phobias, social phobia, fear of public speaking, fear of spiders, panic disorder and post-traumatic stress disorder (PTSD).

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Virtual reality & the treatment of anxiety disorders Rationale

Patients with anxiety disorders usually experience more intense levels of apprehension and worry, which usually occur for longer periods of time than the average person experiences in everyday life and often develop ritual acts, repetitive thoughts or avoidance mechanisms to protect themselves from anxiety. Together with cognitive therapy, behavioral therapy and medication, one of the most effective treatments of anxiety is exposure therapy. Exposure therapy is a process in which a person is exposed to specific feared situations or objects that trigger anxiety. The exposure process may be performed through actual exposure, with visualization or by imagination. The rationale behind exposure therapy is that, by practicing exposure to their fears, people have the opportunity to learn that their fears are excessive, and that anxiety decreases with more and more

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Applications

• It is highly cost-effective

Starting from 1995, different experimental studies have been conducted in order to investigate the effect of VRET in the treatment of specific phobias (acrophobia, claustrophobia, fear of flying, fear of driving and spider phobia) and anxiety disorders (social phobia, panic disorders with agoraphobia and PTSD; for other reviews on the use of VRET in anxiety disorders see [27–36]). The overall objective of this review is to present published journal articles that examined the effects of VRET in the treatment of anxiety and phobic symptoms. A preliminary article search was conducted using MedLine, PsycLIT and ISI Web of Science electronic database. Standard searches were performed, which used keywords related to VRET and anxiety. Reference lists of collected papers were also visually inspected to locate any cited journal articles addressing anxiety and phobic symptoms before and after VRET. For clarity, appendices summarizing the case and randomized controlled studies for each specific phobia or anxiety disorder, each with a brief comment about the efficacy of VRET, are provided.

• The different components of the flight (engines off/on, taxiing, take-off, flying and landing) can be repeated endlessly in the therapist office • Weather conditions can be easily changed by the therapist

Fear of driving

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The literature shows that VRET could be an effective component in the treatment of fear of flying, being more successful than cognitive and behavioral techniques [23,53–65]. However, in order to strengthen the present results, it could be useful to perform new studies comparing different treatment forms, including comparable treatment conditions (same number and length of sessions, VEs that replicate in vivo situations and so on).

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Driving phobia, defined as a specific phobia, situational type in Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, is characterized by intense and persistent fear of driving, which increases as a person anticipates or is exposed to driving stimuli. People with driving phobia acknowledge that their fears are excessive or unreasonable, yet are unable to drive, or tolerate driving with considerable distress. The inability to drive results in a major loss of mobility and independence, which interferes with daily activities. Currently, the only three studies we have found in literature suggest that VRET may be a quite promising intervention for treating driving phobia [66–68], but obviously, more controlled trials and follow-up evaluations are necessary to support these preliminary findings (APPENDIX 4).

Acrophobia

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Acrophobia, that is the pathological fear of heights, was the first phobia treated with VRET (APPENDIX 1). The results of case studies as well as of different controlled studies have shown that it may be reduced by VRET [37–46]. Follow-up observations seem to prove that the effects of the treatment are lasting [47–49]. Claustrophobia

Spider phobia

Fear of flying

Fear of public speaking

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Only two studies have been performed on the effectiveness of VRET in claustrophobia: one is a case study [50] and the other includes only four subjects (three of whom were patients with panic disorder and claustrophobic symptoms) [51] (APPENDIX 2). Even if these two studies show positive results, they are not enough to affirm that VRET really is effective to treat claustrophobia. Further randomized controlled studies are necessary.

Fear of flying is a fairly common disorder that impacts 10–20% of the US population. It is characterized by the inability to fly or by various degrees of anxiety or stress for those who do fly. Approximately one-half of the patients who experience a fear of flying symptoms meet the criteria of specific phobias; they are fearful of something happening to the aircraft, for example, crashing. The other half of the fear of flying population are agoraphobics, with or without panic disorder; they are fearful of being trapped and having a panic attack [52]. A lot of studies have been performed in order to investigate the possibility of treating fear of flying with the VRET approach (APPENDIX 3). Compared with in vivo exposure, VRET presents the following advantages:

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Augmented VRET, consisting of the possibility to touch real objects (i.e., hairy fabric that gives sensation of feeling a spider) while watching a virtual spider through the HMD, seems to be an effective treatment for spider phobia, as concluded in the three studies presented in APPENDIX 5 [69–71]. However, to strengthen this conclusion, more research and more controlled studies are needed.

Since it has been demonstrated that even a virtual audience can elicit anxiety [72–74], specific anxiety-provoking VEs have been created for the treatment of patients with public speaking fear. The available studies [75–79] show promising results, but also have important limitations, such as the inclusion of nonclinical samples, the use of multimodal intervention and the lack of statistical comparisons (APPENDIX 6). Other randomized controlled studies with a larger number of patients are necessary in order to guarantee the efficacy of VRET in the treatment of this disorder. Panic disorder with agoraphobia

Agoraphobia is defined as the fear of being in places or situations from which escape might be difficult or embarrassing and is often associated with panic disorder. To date, only two studies

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Virtual reality in anxiety disorders

Post-traumatic stress disorder

A brief conclusion

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The few studies conducted in PTSD patients have shown that VRET, combined with relaxation techniques and imaginary exposure, is effective in the treatment of this diffuse disorder (APPENDIX 8) [84–86]. However, other studies are necessary to evaluate the efficacy of VRET compared with the imaginary exposure alone and to investigate the possibility to use it in patients with a PTSD caused by different traumatic events (e.g., car accident, rape or physical attack)

money and time, but also in terms of emotional involvement by the person to whom the therapy is directed. The benefits regard the effectiveness of the treatment: the achievement of the target set in the shortest time possible. As we have discussed above, exposure therapy in anxiety disorders is traditionally carried out ‘in imagination’ or else in the real world (i.e., in vivo). With imagination exposure, the subject is trained to produce the anxiety-provoking stimuli through mental images; with in vivo exposure, the subject actually experiences these stimuli in semistructured situations. Both of these methods present advantages and limitations as regards the cost–benefit ratio. In the first case, the prevalent difficulty is represented by teaching the subject to produce the images that regard experiences associated with anxiety: the majority of failures linked to this therapy are those subjects who present particular difficulties in visualizing scenes of real life. The cost of the application, however, is minimal because the therapy is administered in the physician’s office, thus avoiding situations that might be embarrassing for the patient and safeguarding his privacy. In the second case, the difficulty lies in structuring, in reality, experiences regarding the hierarchically ordered anxietyprovoking stimuli, with the result that the cost in terms of time, money and emotions is high. At the same time, the advantage of contending with real contexts increases the likelihood of effectiveness of the ‘in vivo’ procedure [90]. Using VRET, it is possible to recreate a hierarchy of situations corresponding to reality, which they may experience in an authentic way thanks to the involvement of all their sensorimotor channels. The realistic reproduction of VEs enables the interacting individual to immerse himself in a dimension of real presence. This makes it possible to limit the costs as compared with traditional procedures of treatment and to consolidate the effectiveness of the treatment thanks to the possibility of recreating a ‘3D world’ within the walls of the clinical office [91]. On the other side, the use of VR technology requires skilled therapists able to give patients adequate psychological support and who are trained to interact with VEs.

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support the efficacy of VRET on its own in the treatment of panic disorder with agoraphobia (APPENDIX 7) [80,81]. However, Vincelli [82] and Choi [83] have demonstrated that treatments based on the experiential–cognitive therapy (ECT), a combination of psychoeducation, VR exposure, cognitive therapy, interoceptive exposure, exposure in vivo homework assignments and relapse prevention produces the same results of the traditional cognitive–behavioral therapy, but in a smaller amount of time. Unfortunately, when VR is embedded in a multimodal intervention, such as ECT, inferring any conclusions on its effects as a therapeutic method could be deceptive. In conclusion, VRET seems to be a promising treatment for panic disorder with agoraphobia, but other controlled studies and larger samples are necessary to understand the real advantages of this kind of therapy compared with the traditional cognitive–behavioral treatments.

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The presented data indicate that, in general, VRET seems to be a promising intervention for the treatment of specific phobias and anxiety disorders. However, the small sample sizes used, the substantial number of drop-outs in some VRET studies and the frequent use of multimodal interventions make it necessary to perform more controlled and randomized studies to investigate whether VRET can be recommended for use in clinical practice. Despite these limitations, comforting data come from two very recent meta-analyses [87,88]. The first demonstrates not only that VRET is more effective than no treatment, but also that it is slightly but significantly more effective than in vivo exposure. The other analysis, concerning the affective effects of VRET, suggests that it has a statistically large effect on all affective domains and that these effects are of the magnitude described in the literature as large [89]. Expert commentary Cost–effectiveness ratio

One of the fundamental parameters in assessing the effectiveness of therapies is the ratio existing between the ‘cost’ of administration of the therapeutic procedure and the resulting ‘benefits’. Cost refers to the expenditure not only in terms of

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Contraindications

Some medical conditions represent significant contraindications for the use of VR. The presence of migraine, headache, seizure disorder and vestibular abnormalities must be investigated before VR treatment because it is not compatible with this kind of therapeutic approach. There is also some evidence that the use of 3D environments provokes changes in heart rate, and increases systolic and diastolic blood pressure and oxygen consumption, suggesting caution when these tools are used with patients with hypertension, cardiovascular and circulatory diseases. In addition, since VR might interfere with normal psychological processes, a careful observation is necessary when using it with patients with schizophrenia, or with serious personality disorders who are pathologically predisposed to become confused by real versus virtual worlds [92].

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predicting cybersickness in military pilots and in undergraduate populations [93]. This questionnaire is a reasonable starting point for the assessment of discomfort in patients. Long-term effects

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Very little is known about the long term effects of VR exposure. Ungs reported that a very small number of subjects (4.6% of the sample) experienced VR side effects, including visual flashbacks, balance disorder and lack of hand–eye coordination for longer than 24 h after the conclusion of the session [94]. In some cases, VR induces subjects to confuse the virtual experience with the real one, resembling the effects of drugs such as hallucinogens [95]. When this happens, the main risk is that people may prefer the virtual world to the real one and completely withdraw from society or, if the sense of reality becomes blurred, patients may become unable to distinguish safe from dangerous behaviors. Addiction and social isolation are other risks that are connected to the use of VR, but they are more frequent in children and adolescents [96].

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There is a tendency for some VR users to exhibit symptoms that parallel those of classical motion sickness both during and after the virtual experience. Cybersickness is distinct from motion sickness in that the user is often stationary but has a compelling sense of self motion through moving visual imagery. The symptoms related to cybersickness regard different target areas: visual (visual blurring, double vision, tearing, irritation redness), auditory (tinnitus and decreased hearing), vestibular (dizziness, nausea, vomiting and sweating), CNS (headache, seizures, flashbacks, disorientation and instability), musculoskeletal (neck strain, wrist strain and back pain). Unfortunately, there is currently no foolproof method for eliminating the problem, but a gradual introduction to VEs and shorter exposure time can help to prevent symptoms. Several existing questionnaires can be administered to assess for the risk of cybersickness before the beginning of the treatment. The most commonly used, the Simulator Sickness Questionnaire, has been shown to be a reliable indicator for

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Cybersickness

Figure 2. Screenshot of the NeuroVR Editor.

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Virtual reality in anxiety disorders

Five-year view

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Figure 3. Screenshot of the NeuroVR Player (supermarket).

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Although it is undisputable that VR has come of age for clinical and research applications, the majority of them are still in the laboratory or investigation stage. In a recent review, Riva and colleagues identified different major issues that still limit the use of VR in psychotherapy [97]: • The lack of standardization in VR hardware and software, and the limited possibility of tailoring the VEs to the specific requirements of the clinical or experimental setting [98] • The lack of accepted standards for the ergonomic/usability evaluation of VEs given the clinical nature of the applications and users [99] • The low availability of standardized protocols that can be shared by the community of researchers • The high costs (up to $200,000) required for designing and testing a new clinical VR application • Most VEs in use today are not user-friendly; expensive technical support or continual maintenance are often required

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To address these challenges, the Italian research project FIRB-NeuroTIV is developing NeuroVR 2.0, a cost-free VR platform based on open-source software, that allows nonexpert users to easily modify a VE and to visualize it using either an immersive or nonimmersive system [100]. Most existing VEs for psychotherapy are proprietary and have a closed source, and thus cannot be tailored from the ground up to fit specific needs of different clinical applications [33]. NeuroVR addresses these issues by providing the clinical professional with a cost-free VE editor, which allows nonexpert users to easily modify a virtual scene, to best suit the needs of the clinical setting. Using the NeuroVR Editor (FIGURE 2), the psychological stimuli/stressors appropriate for any given scenario can be chosen from a rich database of 2D and 3D objects, and easily placed into the predesigned virtual scenario by using an icon-based interface (no programming skills are required). In addition to static objects, the NeuroVR Editor allows a transparent alpha channel to be overlaid on the 3D scene videos; that is process useful when rendering image elements in separate passes, combining the resulting multiple 2D images into a single, final image.

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commands, a mouse or a joypad, depending on the hardware configuration chosen. A future goal of the developers is also to provide software compatibility with instruments that allow collection and analysis of behavioral data, such as eye-tracking devices and sensors for psychophysiological monitoring. Currently, the NeuroVR library includes a limited number of VEs addressing specific phobias (e.g., fear of public speaking and agoraphobia) and eating disorders. However, new predesigned environments will be developed in the next few years: it is envisioned that Blender user community, consisting currently of 250,000 people worldwide will contribute to extend the NeuroVR library, developing new VEs which can be tailored by the clinical professionals for a range of clinical and experimental needs. A final critical issue related to the use of VRET in the treatment of anxiety-related disorders is the lack of availability of a VR system in the real life context of the patient: both the cost and the setting of the system limit its use to the healthcare center/hospital/therapist’s office. To overcome this issue, a VRML/X3D exporter for experiencing the environments on the Web and a player for PDAs and smartphones are planned features (FIGURE 4). The final goal is the development of a VRET system able to [101]:

Visual simulation control

• Present and structure emotionally relevant contents in a home setting • Verify the adherence of the patient and eventually alert the patient/therapist • Track in real-time the emotional level of the patient and record it for later assessment by the therapist • Provide a feedback to the patient that is able to help him in coping with the contents

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The editing of the scene is performed in real time, and effects of changes can be checked from different views (frontal, lateral and top). Currently, the NeuroVR library includes different predesigned virtual scenes, representing typical real-life situations, such as a supermarket, an apartment or a park (FIGURE 3). These VEs have been designed, developed and assessed in the past 10 years by a multidisciplinary research team in several clinical trials, which have involved over 400 patients [97]. On the basis of this experience, only the most effective VEs have been selected for inclusion in the NeuroVR library. An interesting feature of the NeuroVR Editor is the ability to add new objects to the database. This feature allows the therapist to enhance the patient’s feeling of familiarity and intimacy with the virtual scene; for example, by using photos of objects/people that are part of the patient’s daily life, thereby improving the efficacy of the exposure. The second main component of NeuroVR is the Player, which allows navigation and interaction with the VEs created using the NeuroVR Editor. The Player offers a set of standard features that contribute to increase the realism of the simulated scene. These include collision and detection to control movements in the environment, realistic walk-style motion, advanced lighting techniques for enhanced image quality and streaming of video textures using an alpha channel for transparency. The Player can be configured for two basic visualization modalities: immersive and nonimmersive. The immersive modality allows the scene to be visualized using a HMD, either in stereoscopic or in mono-mode; compatibility with a headtracking sensor is also provided. In the nonimmersive modality, the VE can be displayed using a desktop monitor or a wall projector. The user can interact with the VE using either keyboard

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Financial & competing interests disclosure

Safety overide

Simulation and patient state log

Biosensor monitoring and analysis Control system

Figure 4. Main features of a future mobile virtual reality exposure therapy system.

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• Automatically contact the therapist if the emotional level of the patient is higher than a preset cut-off value

This paper was supported by the Italian MIUR FIRB Programme through its IVT2010 (RBIN04BC5C) research project and by the European Union “Information Society Technologies – IST” Programme through its INTREPID (IST2002–507464) research project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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Key issues • An emerging new treatment for anxiety disorders is virtual reality exposure therapy (VRET), integrating different virtual reality experiences with traditional cognitive–behavioral techniques. • VRET uses a computer-generated environment to recreate a feared stimulus and provide the opportunity for habituation. • The feeling of actual presence offered by the use of VRET enables the patient to experience the treatment in a more vivid and realistic manner than they could through their own imagination. • Through the use of virtual environments, it is possible to gradually expose the patient to feared situations. • The therapist sees what the patient sees. In this way it is easier to identify the exact stimuli that are causing anxiety in patients. • Patients are more receptive to VRET treatment than imaginal treatment. VR therapy appears to have more face validity for them, increasing the adherence to treatment. • VR allows the situation to be graded so that the patient can start at the easiest level and progress to the most difficult.

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• Different controlled studies have verified the efficacy of VRET in different anxiety disorders: simple phobias, panic disorders with agoraphobia, post-traumatic stress disorders and fear of public speaking. • A new open source software, NeuroVR, provides the therapist with an easy way to test this approach in his/her own clinical practice. Steuer JS. Defining virtual reality: dimensions determining telepresence. J. Comm. 42(4), 73–93 (1992).

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Papers of special note have been highlighted as:

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Riva G, Gamberini L. Virtual reality in telemedicine. Telemedicine Journal 6(3), 325–338 (2000).

16 Rubino F, Soler L, Marescaux J, Maisonneuve H. Advances in virtual reality are wide ranging. Br. Med. J. 324(7337), 612 (2002).

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Burdea GC, Coiffet P. Virtual Reality Technology (2nd Edition). Wiley-IEEE Press, New Brunswick, NJ, USA (2003).

17 McCloy R, Stone R. Science, medicine, and the future. Virtual reality in surgery. Br. Med. J. 323(7318), 912–915 (2001).

7

Brooks FP. What’s real about virtual reality? IEEE Computer Graphics and Applications 19(6), 16–27 (1999).

18 Székely G, Satava RM. Virtual reality in medicine. Br. Med. J. 319(7220), 1305 (1999).

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Being There: Concepts, Effects and Measurements of User Presence in Synthetic Environment. Riva G, Davide F, IJsselsteijn WA (Eds). Ios Press, Amsterdam, The Netherlands (2003).

19 Schultheis MT, Rizzo AA. The application of virtual reality technology in rehabilitation. Rehabil. Psychol. 46(3), 296–311 (2001).



Intriguing elucidation about the concept of presence.

www.future-drugs.com

20 Satava RM, Jones SB. Medical applications of virtual reality. In: Handbook of Virtual Environments: Design, Implementation, and

22 Rizzo AA, Wiederhold B, Riva G, Van Der Zaag C. A bibliography of articles relevant to the application of virtual reality in the mental health field. Cyberpsychol. Behav. 1(4), 411–425 (1998). 23 Wiederhold BK, Jang DP, Gevirtz RG et al. The treatment of fear of flying: a controlled study of imaginal and virtual reality graded exposure therapy. IEEE Trans Inf. Technol. Biomed. 6(3), 218–223 (2002). 24 Vincelli F, Molinari E. Virtual reality and imaginative techniques in clinical psychology. In: Virtual Environments in Clinical Psychology and Neuroscience. Riva G, Wiederhold BK, Molinari E (Eds). IOS Press, Amsterdam, The Netherlands (1998). 25 Wiederhold BK, Gevirtz RG, Wiederhold MD. Fear of flying: a case study using virtual reality therapy with physiological monitoring. Cyberpsychol. Behav. 1(2), 97–104 (1998). 26 Wiederhold BK, Wiederhold MD. A review of virtual reality as a psychotherapeutic tool. Cyberpsychol. Behav. 1, 45–52 (1998). 27 Botella C, Quero S, Banos RM. Virtual reality and psychotherapy. Stud. Health Technol. Inform. 99, 37–54 (2004).

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30 Hodges L, Anderson P, Burdea G. Treating psychological and physical disorders with VR. IEEE Comput. Graph. Appl. 21, 25–33 (2001). 31 Krijn M, Emmelkamp P, Olafsson RP, Biedmond R. Virtual reality exposure therapy of anxiety disorders: a review. Clin. Psychol. Rev. 24, 259–281 (2004). •

Good review about the use of virtual reality in psychotherapy.

32 Pull CB. Current status of virtual reality exposure therapy in anxiety disorders. Curr. Opin. Psychiatry 18, 7–14 (2005). •

Good review about the use of virtual reality in psychotherapy.

33 Riva G. Virtual reality in psychotherapy: review. Cyberpsychol. Behav. 8(3), 220–230 (2005). Good review about the use of virtual reality in psychotherapy.

34 Riva G. Virtual environments in clinical psychology. Psychotherapy Theory Research Practice Training 40(1,2), 1–9 (2003).

43 Krijn M, Emmelkamp PM, Olafsson RP, Schuemie MJ, van der Mast CA. Do selfstatements enhance the effectiveness of virtual reality exposure therapy? A comparative evaluation in acrophobia. Cyberpsychol. Behav. 10(3), 362–370 (2007).

44 North MM, North SM. Virtual environment and psychological disorders. Electronic Journal of Virtual Culture 2(4), 37–42 (1994).

45 North MM, North SM, Coble JR. Virtual Reality Therapy, an Innovative Paradigm. IPI Press, Vienna, Austria (1996). 46 North MM, North SM, Coble JR. Virtual reality therapy, an effective treatment for psychological disorders. In: Handbook of Virtual Environments, Design, Implementation and Applications. Stanney KM (Ed.). Lawrence Erlbaum Associates, NJ, USA (2002).

••

A

36 Wiederhold BK, Wiederhold MD. Virtual Reality Therapy for Anxiety Disorders. American Psychological Association, Washington, DC, USA (2005).

Excellent book introducing the concept of ‘cybertherapy’.

37 Choi YH, Jang DP, Ku JH, Shin MB, Kim SI. Short-term treatment of acrophobia with virtual reality therapy (VRT): a case report. Cyberpsychol. Behav. 4(3), 349–354 (2001). 38 Emmelkamp PM, Bruynzeel M, Drost L, van der Mast CA. Virtual reality treatment in acrophobia: a comparison with exposure in vivo. Cyberpsychol. Behav. 4(3), 335–339 (2001). 39 Hodges L, Rothbaum BO, Kooper R et al. Virtual environments for treating the fear of heights. IEEE Comp. 28, 27–34 (1995).

10

53 Kahan M, Tanzer J, Darvin D, Borer F. Virtual reality-assisted cognitive–behavioral treatment for fear of flying: acute treatment and follow-up. Cyberpsychol. Behav. 3, 387–392 (2000). 54 Klein RA. Virtual reality exposure therapy in the treatment of fear of flying. J. Contemp. Psychother. 30, 195–207 (2000). 55 Maltby N, Kirsch I, Mayers M, Allen GJ. Virtual reality exposure therapy for the treatment of fear of flying: a controlled investigation. J. Consult. Clin. Psychol. 70(5), 1112–1118 (2002). 56 Muhlberger A, Hermann MJ, Wiedemann G, Ellgring H, Pauli P. Repeated exposure of flight phobics to flights in virtual reality. Behav. Res. Ther. 39, 1033–1050 (2001). 57 Muhlberger A, Wiedemann G, Pauli P. Efficacy of a one-session virtual reality exposure treatment for fear of flying. Psychother. Res. 13, 323–336 (2003). 58 North MM, North SM, Coble JR. Virtual reality therapy for fear of flying. Am. J. Psychiatry. 154, 130 (1997). 59 Rothbaum BO, Anderson P, Zimand E et al. Virtual reality exposure therapy and standard (in vivo) exposure therapy in the treatment of fear of flying. Behav. Ther. 37(1), 80–90 (2006).

47 Coelho CM, Santos JA, Silverio J, Silva CF. Virtual reality and acrophobia: one-year follow-up and case study. Cyberpsychol. Behav. 9(3), 336–341 (2006).

60 Rothbaum BO, Hodges L, Anderson P, Price L, Smith S. Twelve-months follow-up of virtual reality and standard exposure therapies for the fear of flying. J. Consult. Clin. Psychol. 70, 428–432 (2002).

48 Emmelkamp PM, Krijn M, Hulsbosch AM et al. Virtual reality treatment versus exposure in vivo: a comparative evaluation in acrophobia. Behav. Res. Ther. 40(5), 509–516 (2002).

61 Rothbaum BO, Hodges L, Smith S, Lee JH, Price L. A controlled study of virtual reality exposure therapy for the fear of flying. J. Consult. Clin. Psychol. 68(6), 1020–1026 (2000).

49 Krijn M, Emmelkamp PM, Biemond R et al. Treatment of acrophobia in virtual reality: the role of immersion and presence. Behav. Res. Ther. 42(2), 229–239 (2004).

62 Rothbaum BO, Hodges L, Watson BA, Kessler CD, Opdyke D. Virtual reality exposure therapy in the treatment of fear of flying: a case report. Behav. Res. Ther. 34(5–6), 477–481 (1996).

ut

35 Zimand E, Anderson P, Gershon G. Virtual reality therapy: innovative treatment for anxiety disorders. Prim. Psychiatry 9, 51–54 (2003).

42 Rothbaum BO, Hodges LF, Kooper R et al. Effectiveness of computer-generated (virtual reality) graded exposure in the treatment of acrophobia. Am. J. Psychiatry 152(4), 626–628 (1995).

ho



41 Rothbaum BO, Hodges L, Kooper R et al. Virtual reality graded exposure in the treatment of acrophobia: a case report. Behav. Ther. 26, 547–554 (1995).

52 McNally RJ, Loura CE. Fear of flying in agoraphobia and simple phobia: distinguishing features. J. Anxiety Disord. 6, 319–324 (1992).

of

29 Gregg L, Tarrier N. Virtual reality in mental health: a review of the literature. Soc. Psychiatry Psychiatr. Epidemiol. 42, 343–354 (2007).

40 Jang DP, Ku JH, Choi YH et al. The development of virtual reality therapy (VRT) system for the treatment of acrophobia and therapeutic case. IEEE Trans. Inf. Technol. Biomed. 6(3), 213–217 (2002).

ro

28 Glantz K, Rizzo A, Graap K. Virtual reality for psychotherapy: current reality and future possibilities. Psychotherapy Theory Research Practice Training 40, 55–67 (2003).

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Review

50 Botella C, Banos RM, Perpina C et al. Virtual reality treatment of claustrophobia: a case report. Behav. Res. Ther. 36, 239–246 (1998). 51 Botella C, Banos RM, Villa H, Perpina C, Garcia-Palacios A. Virtual reality in the treatment of claustrophobic fear: a controlled, multiple-baseline design. Behav. Ther. 31, 583–595 (2000).

63 Wallach HS, Bar-Zvi M. Virtual-realityassisted treatment of flight phobia. Isr. J. Psychiatry Relat. Sci. 44(1), 29–32 (2007). 64 Wiederhold BK, Gevritz R, Wiederhold MD. Fear of flying: a case report using virtual reality therapy with physiological monitoring. Cyberpsychol. Behav. 1, 97–103 (1998).

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Virtual reality in anxiety disorders

65 Wiederhold BK, Wiederhold MD. Threeyear follow-up for virtual reality exposure for fear of flying. Cyberpsychol. Behav. 6(4), 441–446 (2003).

78 Klinger E, Legeron P, Roy S et al. Virtual reality exposure in the treatment of social phobia. Stud. Health Technol. Inform. 99, 91–119 (2004).

66 Wald J. Efficacy of virtual reality exposure therapy for driving phobia: a multiple baseline across-subjects design. Behav. Ther. 35, 621–635 (2004).

79 North M, North SM, Coble JR. Virtual reality therapy: an effective treatment for the fear of public speaking. Int. J. Virt. Reality 3, 2–7 (1998).

67 Wald J, Taylor S. Efficacy of virtual reality exposure therapy to treat driving phobia: a case report. J. Behav. Ther. Exp. Psychiatry 31(3–4), 249–257 (2000).

80 Botella C, Garcia-Palacios A, Villa H et al. Virtual reality exposure in the treatment of panic disorder and agoraphobia: a controlled study. Clin. Psychol. Psychother. 14(3), 164–175 (2007).

70 Garcia Palacios A, Hoffman HG, Carlin AS, Furness TA, Botella C. Virtual reality in the treatment of spider phobia: a controlled study. Behav. Res. Ther. 40, 983–993 (2002).

84 Difede J, Hoffman HG. Virtual reality exposure therapy for World Trade Center post-traumatic stress disorder: a case report. Cyberpsychol. Behav. 5, 529–535 (2002).

85 Rothbaum BO, Hodges L, Alarcon R et al. Vitual reality exposure therapy for PTSD Vietnam veterans: a case study. J. Trauma. Stress 12, 263–271 (1999).

ut

72 Pertaub DP, Slater M, Barker C. An experiment on public speaking anxiety in response to three different types of virtual audience. Presence (Camb.) 11, 68–78 (2002).

A

73 Pertaub DP, Slater M, Barker C. An experiment on fear of public speaking in virtual reality. Stud. Health Technol. Inform. 81, 372–378 (2001). 74 Pertaub DP, Slater M, Barker C. Public speaking in virtual reality: facing an audience of avatars. IEEE Comput. Graph. Appl. 19, 6–9 (1999). 75 Anderson P, Rothbaum BO, Hodges L. Virtual reality exposure in the treatment of social anxiety. Cogn. Behav. Pract. 2003(10), 240–247 (2003). 76 Anderson PL, Zimand E, Hodges LF, Rothbaum BO. Cognitive behavioral therapy for public-speaking anxiety using virtual reality for exposure. Depress. Anxiety 22(3), 156–158 (2005). 77 Harris SR, Kemmerling RL, North MM. Brief virtual reality therapy for public speaking anxiety. Cyberpsychol. Behav. 5(6), 543–550 (2002).

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89 Cohen J. A power primer. Psychol. Bull. 112, 155–159 (1992). 90 Vincelli F, Riva G. Virtual reality: a new tool for panic disorder therapy. Exp. Rev. Neurotherapeutics 2(3), 377–383 (2002). 91 Vincelli F, Anolli L, Bouchard S et al. Experiential cognitive therapy in the treatment of panic disorders with agoraphobia: a controlled study. Cyberpsychol. Behav. 6(3), 312–318 (2003). 92 Cartwright GF. Virtual or real? The mind in cyberspace. The Futurist 28(2), 22–26 (1994). 93 Stanney KM, Kennedy RS. The psychometrics of cybersickness. Commun. ACM 40(8), 67–68 (1997).

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83 Choi YH, Vincelli F, Riva G et al. Effects of group experiential cognitive therapy for the treatment of panic disorder with agoraphobia. Cyberpsychol. Behav. 8(4), 387–393 (2005).

ho

71 Hoffman HG, Garcia Palacios A, Carlin AS, Furness TA, Botella C. Interfaces that heal: coupling real and virtual objects to treat spider phobia. Int. J. Hum. Comput. Interact. 16, 283–300 (2003).

82 Vincelli F, Anolli L, Bouchard S et al. Experiential cognitive therapy in the treatment of panic disorders with agoraphobia: a controlled study. Cyberpsychol. Behav. 6(3), 321–328 (2003).

ro

69 Carlin AS, Hoffman HG, Weghorst S. Virtual reality and tactile augmentation in the treatment of spider phobia: a case report. Behav. Res. Ther. 35(2), 153–158 (1997).

81 North M, North SM, Coble JR. Effectiveness of virtual environment desensitization in the treatment of agoraphobia. Presence (Camb.) 5, 346–352 (1996).

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68 Walshe DG, Lewis EJ, Kim SI, O’Sullivan K, Wiederhold BK. Exploring the use of computer games and virtual reality in exposure therapy for fear of driving following a motor vehicle accident. Cyberpsychol. Behav. 6(3), 329–334 (2003).

Review

86 Rothbaum BO, Hodges L, Ready D, Graap K, Alarcon R. Virtual reality exposure therapy for Vietnam veterans with posttraumatic stress disorder. J. Clin. Psychiatry 62, 617–622 (2001). 87 Powers MB, Emmelkamp PM. Virtual reality exposure therapy for anxiety disorders: a meta-analysis. J. Anxiety Disord. (2007) (Epub ahead of print). ••

Excellent meta-analysis about the effects of virtual reality exposure therapy in anxiety disorders.

88 Parsons TD, Rizzo A. Affective outcomes of virtual reality exposure therapy for anxiety and specific phobia: a meta-analysis. J. Behav. Ther. Exp. Psychiatry (2007) (Epub ahead of print). •

Good meta-analysis describing the affective outcomes of virtual reality exposure therapy.

94 Ungs TJ. Simulator induced syndrome: evidence for long-term aftereffects. Aviat. Space Environ. Med. 60(3), 252–255 (1989). 95 Mantovani G. Virtual reality as a communication environment: consensual hallucination, fiction, and possible selves. Hum. Relat. 48, 669–683 (1995). 96 Plusquellec M. Are virtual worlds a threat to the mental health of children and adolescents? Arch. Pediatr. 7(2), 209–210 (2000). 97 Cybertherapy: Internet and Virtual Reality as Assessment and Rehabilitation Tools for Clinical Psychology and Neuroscience. Riva G, Botella C, Légeron P, Optale G (Eds). IOS Press, Amsterdam, The Netherlands (2004). •

Key book about cybertherapy.

98 Botella C, Baños R, Guerrero B et al. Using a flexible virtual environment for treating a storm phobia. PsychNol. J. 4(2), 129–144 (2006). 99 Galimberti C, Belloni G, Cantamesse M et al. The development of an integrated psychosocial approach to effective usability of 3D Virtual Environments for Cybertherapy. PsychNol. J. 4(2), 161–180 (2006). 100 Riva G, Gaggioli A, Villani D et al. NeuroVR: an open source virtual reality platform for clinical psychology and behavioral neurosciences. Stud. Health Technol. Inform. 125, 394–399 (2007). ••

Excellent paper describing the NeuroVR software.

101 Riva G, Grassi A, Villani D, Preziosa A. Cellular phones for reducing battlefield stress: rationale and a preliminary research. Stud. Health Technol. Inform. 125, 400–405 (2007).

11

Review

Gorini and Riva



Affiliations •

Alessandra Gorini, MSc Applied Technology for Neuro-Psychology Lab, Istituto Auxologico Italiano, Via Pelizza da Volpedo, 41. 20149 Milan, Italy; Research Institute Brain and Behaviour, Maastricht University, The Netherlands Tel.: +39 02 619112726 Fax: +39 02 619112892 [email protected]

Giuseppe Riva, PhD Applied Technology for Neuro-Psychology Lab, Istituto Auxologico Italiano, Via Pelizza da Volpedo, 41. 20149 Milan, Italy; Psychology Department, Catholic University of Milan, Italy

Appendices

• Appendix 1: Acrophobia • Appendix 2: Claustrophobia • Appendix 3: Fear of flying • Appendix 4: Fear of driving • Appendix 5: Spider phobia • Appendix 6: Fear of public speaking • Appendix 7: Panic disorder with agoraphobia

A

ut

ho

rP

ro

of

• Appendix 8: Post-traumatic stress disorder

12

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20, 3 drop-outs (nonclinical sample)

1 (clinical sample)

10 (clinical sample)

38, 5 drop-outs (clinical sample)

1 (clinical sample)

37, 12 drop-outs (clinical sample)

Rothbaum et al. (1995)

Choi et al. (2001)

Emmelkamp et al. (2001)

Emmelkamp et al. (2002)

Jang et al. (2002)

Krijn et al. (2004)

Randomized crossover design

Krijn et al. (2007)

ut 1

3

2+2

6

8

3

2 (VRET followed by 2 + 2 VRET + VRET-CSS vs VRET + VRET-CSS followed by VRET)

1 (VRET)

3 (VRET with HMD vs 3 VRET with CAVE vs WL)

1

2 (VRET vs IVE)

5

6

8

Reduction of fear and avoidance; symptom improvement

Reduction of anxiety and avoidance; symptoms improvement

Reduction of anxiety and symptoms

VRET = VRET-CSS

At 6-month follow-up, most gains during treatment were not fully retained

Significant improvements in Stable results at every post-test measure, in 1-year follow-up behavioral performance, in the subjective feeling of fear and in the attitudes towards heightrelated situations for all subjects

VRET-HMD = VRET-CAVE Stable results at VRET-HMD and VRET-CAVE > WL 6-month follow-up

of

Stable results at 6month follow-up

Stable results at 6-month follow-up

Follow-up

ro

Symptom improvement

VRET = IVE in reduction of anxiety and avoidance

VRET = IVE in reduction of anxiety and avoidance

Reduction of anxiety and avoidance; symptom improvement

rP

VRET > WL on all subjective measures of anxiety and avoidance

ho

2 (VRET followed by IVE)

1

2 (VRET vs CTR)

1

1

2 (VRET vs CTR)

Sessions Short-term outcome

VRET, regardless of addition of coping self-statements, decreased anxiety and avoidance of height situations, and improved attitudes towards heights

The level of immersion (HMD vs CAVE) does not influence the effectiveness of the treatment

Order effect cannot be ruled out

Seven of 12 students exposed themselves to height situations in vivo between sessions that probably influenced the results

Acrophobic subjects were included in agoraphobia group (24/30)

Notes and limitations

[43]

[47]

[49]

[40]

[48]

[38]

[37]

[42]

[41]

[39]

[44]

Ref.

CAVE: Cave Automatic Virtual Environment; CTR: No-treatment control group; HMD: Head-mounted display; IVE: In vivo exposure; VRET-CSS: Virtual reality exposure therapy + coping self statements; WL: Waiting list (patients waiting for the treatment) VRT: Virtual reality therapy; VRET: Virtual reality exposure therapy.

26 (clinical sample)

Uncontrolled study

Coelho et al. 10 (clinical (2006) sample)

Randomized controlled study; between subjects design

Case study

Randomized controlled study; between subjects design

Within subjects design

Case study

Randomized controlled study; between subjects design

Case study

1 (clinical sample)

Rothbaum et al. (1995)

Condition(s)

A

Randomized controlled study; between subjects design

Case study

24 (clinical sample)

North et al. (1994)

Design

Hodges et al. 1 (clinical (1995) sample)

Samples

Study

Appendix 1. Acrophobia.

Virtual reality in anxiety disorders

Review

13

14

Samples

31, Uncontrolled 6 drop-outs study (clinical sample)

Kahan et al. (2000)

A

Case study

Case study

1

5

2 (within subject: AMT + VRET)

rP

21 (3 AMT + After treatment, the patient was 18 VRET) + able to fly with a reduction of homework fear and anxiety

of

Patients continued to fly but with anxiety

ro

68% of treated patients were able to make a real flight after treatment. No other measures were reported

Reduction in skin conductance immediately after the session

Gradual reduction of discomfort during sessions; symptom improvement; participant could fly comfortably in vivo after treatment

Multimodal intervention: the different treatment components were not evaluated separately

Results were not presented for each treatment separately; there were no subjective or objective measures of subjects’ anxiety; some patients took medication or other psychological treatments before and/or during treatment; so any conclusion about the effectiveness of VRET is precluded

Both components were effective

Notes and limitations

A multiple baseline showed fluctuations in scores for 2 of the patients, indicating lack of stability of symptom severity before treatment; VRET was not compared with other treatments

Notes and limitations

Follow-up

Stable results at 1- and 3-month follow-ups

Stable results at 1-month follow-up

Reduction of discomfort, anxiety, avoidance and depression; symptom improvement; the participant could fly comfortably in vivo after treatment

Short-term outcome

Reduction of anxiety and avoidance; symptom improvement

ho

7 AMT followed by 6 VRET

Sessions

1 (AMT + VRET) Average of 5.75

1 (VRET)

1

2 (within subject: AMT + VRET)

Condition(s)

ut

8

Reduction of anxiety and avoidance; symptoms improvement

Follow-up

[54]

[53]

[64]

[58]

[62]

Ref.

[51]

[50]

Ref.

AMT: Anxiety management training (cognitive and relaxation techniques and psycho-education); APGT: Attention-placebo group treatment; CBT: Cognitive–behavioral therapy (cognitive restructuring, interoceptive exposure and imaginative exposure to feared situations); IET: Systematic desensitization with imaginal exposure therapy; IVE: In vivo Exposure; WL: Waiting list (patients waiting for the treatment); VRET: Virtual reality exposure therapy.

1 (clinical sample)

2 (1 phobic Uncontrolled + 1 normal) study

Wiederhold et al. (1998)

Klein (2000)

1 (clinical sample)

North et al. (1997)

Case study

1 (clinical sample)

Rothbaum et al. (1996)

Design

Samples

Study

Appendix 3. Fear of flying.

IVE: In vivo exposure.

1 (VRET)

8 + 1 IVE

Condition(s) Sessions Short-term outcome

Case study 1

Design

Botella et al. 1 claustrophobic + Multiple(2000) 3 panic disorder baseline with claustrophobic design fear (clinical sample)

Botella et al. 1 (clinical sample) (1998)

Study

Appendix 2. Claustrophobia.

Review Gorini and Riva

Expert Rev. Neurotherapeutics 8(2), (2008)

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45, 4 drop-outs (clinical sample)

30, 10 drop-outs (clinical sample)

Rothbaum et al. (2000)

Muhlberger et al. (2001)

A

Sessions

ut

Condition(s)

2 (AMT followed by VRET vs AMT followed by relaxation)

5

At 3-month follow-up, only Physiological feedback may one participant who received add to the efficacy of VR IET, eight of the 10 treatment participants who received VRGET with no physiological feedback, and 10 of the 10 participants who received VRGET with physiological feedback, reported an ability to fly without medication or alcohol

of

Educational and nonspecific factors seem to have a relatively large impact on flying behavior and fear of flying. Nonetheless, for APGT participants only, degree of anxiety reported at posttreatment was unrelated to the ability to fly successfully. In contrast, reduced scores on measures of flight anxiety for VRET participants was significantly associated with successfully flying

VRET situations (virtual flight, taxiing, take-off and landing) were different from IVE situations (walking through an airport and sitting in a stationary aircraft)

Notes and limitations

[23]

[60]

[55]

[56]

[61]

Ref.

AMT: Anxiety management training (cognitive and relaxation techniques and psycho-education); APGT: Attention-placebo group treatment; CBT: Cognitive–behavioral therapy (cognitive restructuring, interoceptive exposure and imaginative exposure to feared situations); IET: Systematic desensitization with imaginal exposure therapy; IVE: In vivo Exposure; WL: Waiting list (patients waiting for the treatment); VRET: Virtual reality exposure therapy.

VRET with physiological feedback >VRET with no physiological feedback >IET

At 12-month follow-up; AMT+VRET = AMT+IVE

At 6-month follow-up, most group differences disappeared; VRET resulted in a better outcome on only one of five standardized flight anxiety measures

No differences between the two treatments; stable results at 1-year follow-up, although a significant number of patients reported using either alcohol or drugs to reduce anxiety on flights

Follow-up

ro

65% of VRET and 57% of APGT participants flew during a test flight. Both groups showed significant improvement following treatment on standardized self-report measures of flight anxiety, with a better outcome for the VRET group on four of five of these measures

rP

VRET > RELAXATION on fear of flying questionnaire; VRET = RELAXATION on the other measurements

AMT+VRET = AMT+IVE; AMT+VRET > WL; AMT+IVE > WL

Short-term outcome

ho

4 h AMT followed by 4 simulated flights vs 4 h AMT followed by 2 relaxation sessions

3 (VRET with no 8 physiological feedback vs VRET with physiological feedback vs IET)

30 (clinical sample)

Wiederhold et al. (2002)

Randomized controlled study; between subjects design

24, 12-month 2 (AMT + VRET 6 drop-outs follow up study vs AMT + IVE) [61] (clinical sample)

Randomized 2 (AMT + VRET controlled vs APGT) study; between subjects design

Randomized partly uncontrolled study; between subjects design

Randomized 3 (AMT + VRET 8 (4 AMT + controlled vs AMT + IVE vs 4 VRET or study; between WL) IVE) subjects design

Design

Rothbaum et al. (2002)

Maltby et al. 45 (clinical (2002) sample)

Samples

Study

Appendix 3. Fear of flying (cont.).

Virtual reality in anxiety disorders

Review

15

16

45, 8 drop-outs (clinical sample)

30 (clinical sample)

83, 8 drop-outs (clinical sample)

4 (clinical sample)

Muhlberger et al. (2003)

Wiederhold et al. (2003)

Rothbaum et al. (2006)

Wallach et al. (2007)

rP

Uncontrolled, pilot study

1 (VRET)

Reduction of anxiety and fear; symptoms improvement; the participants could fly in vivo after treatment

of

Stable results at 6- and 12-month follow-ups for >70% of respondents

Stable results at 6-month follow-up

Follow-up

ro

Of the participants in the VRGET group who had flown successfully by the end of treatment, all had maintained their ability to fly at follow-up. Of the participants in the VRGETno group who had flown successfully by the end of treatment, two were no longer able to fly. Of the participants in the IET group who had flown successfully, all were still able to fly

CBT + VRET > CBT > WL

Short-term outcome

ho

1 h CBT followed by 4 simulated flights (with or without motion simulation) vs 1 h CBT

Sessions

ut

3 (VRET with physiological and visual feedback vs VRETno vs IET with physiological feedback only)

A

4 (CBT + VRET with motion simulation vs CBT + VRET without motion simulation vs CBT vs WL)

Condition(s)

Randomized 3 (AMT + VRET 10 (4 AMT + AMT+VRET = AMT+IVE controlled vs AMT + IVE vs 6 VRET or AMT+VRET > WL study; between WL) IVE) AMT+IVE > WL subjects design

3-year follow up study

Randomized controlled study: between subjects design

Design

Small sample size; lack of a control group; lack of objective measures

The addition of teaching selfcontrol via visual feedback of physiological signals serves to maintain treatment gains in long-term follow-up

Motion simulation did not enhance treatment effectiveness; CBT condition took only 1 h while CBT + VRET took approximately 140 min

Notes and limitations

[63]

[59]

[65]

[57]

Ref.

AMT: Anxiety management training (cognitive and relaxation techniques and psycho-education); APGT: Attention-placebo group treatment; CBT: Cognitive–behavioral therapy (cognitive restructuring, interoceptive exposure and imaginative exposure to feared situations); IET: Systematic desensitization with imaginal exposure therapy; IVE: In vivo Exposure; WL: Waiting list (patients waiting for the treatment); VRET: Virtual reality exposure therapy; VRETno: VRET without visual feedback.

Samples

Study

Appendix 3. Fear of flying (cont.).

Review Gorini and Riva

Expert Rev. Neurotherapeutics 8(2), (2008)

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8

1 (clinical sample)

Carlin et al. (1997)

Significant improvement in driving anxiety and avoidance in three patients; marginal improvement in one patient and no treatment gains in the last patient

rP

Significant reduction of distress, fear of diving, posttraumatic stress and depression

8 clinically Randomized controlled phobic and study; between 28 nonclinical subjects design students

Randomized controlled study; between subjects design

Case study

Design 12

3 (VRET 3 augmented vs VRET vs WL)

Half of the patients did not demonstrate an anxiety response during the VR exposure; multimodal intervention: the different treatment components were not evaluated separately

Notes and limitations

VRET augmented > VRET > WL in reduction of behavioral avoidance and subjective fear

Tactile augmentation makes the VRET more effective

Paradigm based on VRET with tactile augmentation

Paradigm based on VRET with tactile augmentation

Follow-up Notes and limitations

of Reduction of fear, anxiety and avoidance; symptom improvement

Short-term outcome

ro

Some loss of treatment Only little change in actual gains at 3-months driving frequency for any of the follow-up, but the scores patients remained below the pretreatment levels

2 (VRET Average of 4 VRET augmented > WL; 83% of the augmented vs VRET group showed a significant CTR) reduction of fear, anxiety and avoidance

1

Condition(s) Sessions

CTR: No-treatment control group; WL: Waiting list (patients waiting for the treatment); VRET: Virtual reality exposure therapy.

Hoffman et al. (2003)

Garcia-Palacios 23 (clinical et al. (2002) sample)

Samples

Study

Appendix 5. Spider phobia.

Follow-up

Peak anxiety decreased within Stable results at 1- and and across sessions; anxiety 7-month follow-ups and avoidance and phobiarelated interference in daily functioning declined between pre- and post-treatment

ho

12

ut

1 (CBT + VRET)

5 (clinical sample) Multiple 1 (VRET) baseline across subjects design

Open trial

A 1

3

Condition(s) Sessions Short-term outcome

CBT: Cognitive behavioural therapy (cognitive restructuring, interoceptive exposure, and imaginative exposure to feared situations).

Wald (2004)

Walshe 14, 7 drop-outs et al. (2003) (patients with driving phobia following a motor-vehicle accident)

1 (clinical sample) Case study

Wald et al. (2000)

Design

Samples

Study

Appendix 4. Fear of driving.

[71]

[70]

[69]

Ref.

[66]

[68]

[67]

Ref.

Virtual reality in anxiety disorders

Review

17

18

ut

Controlled not randomized study; between subjects design

Open clinical trial 1 (AMT + VRET) 4 AMT + 4 VRET

Anderson 10 (clinical et al. (2005) sample)

ro

Decreases on all self-report Stable measures of public-speaking results at anxiety from pre- to post-treatment 3-month follow-up

VRET = CBGT (no statistical comparison)

Followup

Uncontrolled study; multimodal intervention: the different treatment components were not evaluated separately

Statistical comparisons were not made; participants were not randomly allocated

Multimodal intervention: the different treatment components were not evaluated separately

Multimodal intervention: the different treatment components were not evaluated separately

Nonclinical sample

Nonclinical sample

Notes and limitations

[76]

[78]

[75]

[75]

[77]

[79]

Ref.

of

AMT: Anxiety management training (cognitive and relaxation techniques and psychoeducation); CBGT: Cognitive–behavioral group therapy; CTR: No-treatment control group; CTR*: Control group (subjects were exposed to a trivial VR scene and encouraged to manage their phobia using visualization techniques or self exposure to the feared situations); IVE: In vivo exposure; IVT: Talking in front of a video camera and watching the videotape; VRET: Virtual reality exposure therapy.

2 (VRET + IVE vs 12 CBGT + IVE)

rP

Decline in specific anxiety symptoms

ho

VRET > CTR; significant reduction of anxiety in the VRET group

VRET > CTR; significant reduction of anxiety and increased ability to face real world situations in the VRET group; no changes in the CTR group

Short-term outcome

2 IVT + 5 VRET Decline in specific anxiety + 1 relapse symptoms prevention

Klinger 36 (clinical et al. (2004) sample)

1

4 AMT + 1 IVT + 4 VRET

4

Case study

1

Randomized 2 (VRET vs CTR) controlled study; between subjects design

A

5

Sessions

Anderson 1 (clinical et al. (2003) sample)

14 (nonclinical sample)

Harris et al. (2002)

Randomized 2 (VRET vs controlled study; CTR*) between subjects design

Condition(s)

Case study

16, 2 drop-outs (nonclinical sample)

North et al. (1998)

Design

Anderson 1 (clinical et al. (2003) sample)

Samples

Study

Appendix 6. Fear of public speaking.

Review Gorini and Riva

Expert Rev. Neurotherapeutics 8(2), (2008)

www.future-drugs.com

60 (nonclinical students with some degree of agoraphobia)

7, 7 drop-outs (clinical sample)

12 (clinical sample)

40 (clinical sample)

37 (clinical sample)

North et al. (1996)

Jang et al. (2000)

Vincelli et al. (2003) (also see [91]

Choi et al. (2005)

Botella et al. (2007)

ut

2 (VRET vs CTR)

Randomized controlled study; between subjects design

3 (VRET vs IVE 9 vs WL)

Randomized 2 (ECT vs PCP) ECT = 4; controlled study; PCP = 12 between subjects design

rP

ro

At 6-month follow-up: PCP > ECT

Follow-up

VRET = IVE ; VRET > WL ; Stable results at IVE > WL 1-year follow-up

ECT = PCP

ECT = CBT; ECT > WL; CBT > WL; ECT and CBT reduced the number of panic attacks, the level of depression and both state and trait anxiety

VRET > CTR; significant decrease in negative attitudes towards agoraphobic situations for VRET group

ho

Open 1 2 uncontrolled study Randomized 3 (ECT vs CBT ECT = 8; controlled study; vs WL) CBT = 12 between subjects design

Randomized controlled study; between subjects design

8

Condition(s) Sessions Short-term outcome

A

Experimental design

Multimodal intervention: the different treatment components were not evaluated separately; ECT produced the same results of using 33% fewer sessions than PCP immediately after the treatment, but the effect was not retained at 6-month follow-up

Participants were not able to feel present in the virtual environment; the study was stopped Small sample size; multimodal intervention: the different treatment components were not evaluated separately; ECT produced the same results of using 33% fewer sessions than CBT

Nonclinical sample

Notes and limitations

[80]

[83]

[82]

[81]

Ref.

6

1

90% reduction of PTSD symptoms after completing the VRET

Participant experienced a 34% decrease on clinically-rated PTSD and a 45% decrease on self-rated PTSD; global symptom improvement Significant reduction in symptoms associated with reported traumatic experiences

Short-term outcome

Stable results at 6-month follow-up

Stable results at 6-month follow-up

Follow-up

of

IET: Systematic desensitization with imaginal exposure therapy; PE: Psychoeducation; PTSD: Post-traumatic stress disorder; VRET: Virtual reality exposure therapy.

8–16

1 (VRET + IET + PE + relaxation)

14

Condition(s) Sessions

Rothbaum 16, 7 drop-outs Open clinical trial et al. (2001) (Vietnam combat veterans) Difede et al. 1 (survivor of Case study (2002) the World Trade Center attack)

Design 1

Samples

Rothbaum 1 (Vietnam Case study et al. (1999) combat veteran)

Study

Appendix 8. Post-traumatic stress disorder.

Uncontrolled study; multimodal intervention: the different treatment components were not evaluated separately

Multimodal intervention: the different treatment components were not evaluated separately

Notes and limitations

[84]

[86]

[85]

Ref.

CBT: Cognitive–behavioral therapy (cognitive restructuring, interoceptive exposure and imaginative exposure to feared situations); CTR: No-treatment control group; ECT: Experiential cognitive therapy (psychoeducation, virtual reality exposure, cognitive therapy, interoceptive exposure, exposure in vivo homework assignments and relapse prevention); IVE: In vivo exposure; PCP: Panic control program; WL: Waiting list (patients waiting for the treatment); VRET: Virtual reality exposure therapy.

Samples

Study

Appendix 7. Panic disorder with agoraphobia.

Virtual reality in anxiety disorders

Review

19

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