In 2017, while deploying the on-demand, library-based VR-delivered content to clinics and hospitals, the company received a request to help a patient experiencing severe chronic pain after being involved in a traumatic accident. The patient was sent the Samsung Gear VR kit, was trained to use the device, and was informed that the VR content could be used to help cope with pain flare ups, enhance relaxation and reduce stress in the moment. Interestingly, periodic follow-up with the patient revealed that they were not just using the device for temporary pain relief but rather were using the device to learn and retain pain management skills that persisted beyond the VR sessions (Follow this link or this link for more details regarding this patient).

This fortuitous event made clear the potential opportunity to target chronic pain with in-home VR-delivered therapy. To explore this possibility, the first step was to bring prototype modules into pain clinics and to conduct usability testing with patients and providers. Briefly, the prototype device included several diaphragmatic breathing, mindfulness and distraction modules. Two critical learnings from this user testing stand out. First, simplified content was found to be superior. Simple breathing-based biofeedback was valuable, but extensively gamified interaction was overly complex and unnecessary. Second, the value of therapeutic content repetition, spaced over time, was clear, in particular, when it came to diaphragmatic breathing and the development of long-term pain management skills. This led to the development of an 8-session VR-delivered therapy focused on helping patients develop diaphragmatic breathing techniques for managing chronic pain when outside of VR (see Figure 3).

Although the Samsung Gear VR posed technical challenges for in-home use, in 2018 a small-scale in-home feasibility study was conducted with the 8-session deep breathing-based VR-delivered VR therapy in 35 chronic pain sufferers. Patients were shipped a device, received training over the phone on use of the device along with a technical support number to call should problems arise, and used the device for 8-day with the ability to repeat experiences if desired. Patients were asked to rate their pain, anxiety, mood and sleep at baseline and at the end of the 8 days with the therapy. On average, pain was reduced by 1.3 points, anxiety was reduced by 1.4 points, mood was enhanced by 2.0 points and sleep was enhanced by 1.3 points (all on 0–10-point scales).

In 2019, while developing and testing the 8-session VR-delivered breathing therapy, AppliedVR was introduced to Dr. Beth Darnall, a pain psychologist at Stanford University School of Medicine. Dr. Darnall saw the potential of VR-delivered therapy for chronic pain and entered an advisory role with the company to develop the next iteration of the VR-delivered therapy. Dr. Darnall advocated for a multi-modal therapeutic approach that integrated diaphragmatic breathing, biofeedback, cognition and emotion regulation, mindfulness, and pain education. Like in-office pain treatments with standardization facilitating treatment testing, Dr. Darnall also advocated for a fixed therapeutic sequence of VR-delivered content that followed a rigorous therapeutic journey as opposed to a user-selected approach. The result was a 21-session, multi-modal, fixed sequence VR-delivered skills-based therapy for cLBP. The skills-based program involved a range of sessions lasting between two and 15 min that guided participants through pain self-management skills that form a part of CBT programs (e.g., adaptive regulation of pain-related cognition and emotions), as well as relaxation training (diaphragmatic breathing exercises to enhance parasympathetic nervous system function), and mindfulness.

While the 21-session VR-delivered program was being developed, the Oculus Go VR headset was also gaining traction in the market. The Oculus Go VR headset was notable because it was the first commercially available standalone headset that did not require connecting a phone into a holder or using a head mounted display tethered to a computer. With the 21-session program deployed on the Oculus Go headset, a small-scale in-home pilot randomized controlled trial was launched. A total of 97 participants who were living with cLBP or fibromyalgia for at least 6 months were consented into the study and were assigned to either the 21-session skills-based VR program or an audio-only version of the VR program (Darnall et al., 2020) to be completed at home. A sample headset and VR content are displayed in Figure 4.

Both groups saw decreases in pain intensity and pain interference over the course of the 21-session intervention, although the average effects were statistically larger for the VR-delivered therapy group compared to the audio-only group. Baseline pain intensity and the four pain interference measures were moderate, ranging from 4.6 to 5.4 on a 0–10-point scale. The study revealed a 1.4-point reduction in pain intensity, and a 1.8-, 2.1-, 2.7-, and 2.6-point reduction in pain interference with activity, sleep, mood and stress, respectively. The pain intensity and composite pain interference reductions for the 21-session VR-delivered therapy are presented in Table 3. (Table 3 includes pain reductions, VR therapeutic engagement and system usability scores across several AppliedVR conducted studies). Engagement with the VR-delivered therapy was strong. Participants were given a 21-session therapy but were allowed to repeat experiences at any time and utilized this option, completing an average of 34.4 experiences. Critically, these data were included in a successful submission to the FDA that secured breakthrough designation for the 21-session VR-delivered therapy for cLBP and fibromyalgia.

A decision was made to migrate from the Oculus Go to the Pico G2 4K for the next version of the VR-delivered therapy. The Pico G2 4K was already being used successfully for the on-demand, library-based product. It was gaze-based, with a user-friendly navigation experience, a high resolution 4K screen, and an easily wipeable face pad. For the VR-delivered therapy, a proprietary breathing shield amplifier and breath-capture algorithm was added to help visualize the patient’s breathing pattern and to use their breathing pattern to interactively modify the ongoing VR experience. The therapy was also expanded from a 21-session to a 56-session, fixed sequence VR-delivered therapy with more varied and higher resolution VR content. (Several possibilities for further refinement of the VR-delivered therapy are discussed in the Future Directions). The 56 sessions were organized into 8 weekly themes, such as “Breath and Pain”, “Attention and Distraction, and “Shaping the Nervous System Toward Relief” to name a few. Each week users experienced a range of session content. This included pain education that provided a medical and scientific rationale for the VR experiences, relaxation/interoception scenes that progressively change from busy/active to calm to train users to understand the benefits of progressive relaxation, 360-degree mindful escape videos designed to maximize the relaxation response and participant engagement, interactive pain distraction content to train the skill of shifting focus away from pain, and dynamic breathing to support self-regulation and relaxation with modules becoming increasingly challenging as users increase their skill with diaphragmatic breathing and parasympathetic control. Crucially, the 56-session treatment included interoceptive modules that were designed for more rapid entrainment of CNS downregulation via vivid and frequent enhanced biofeedback experiences. The 56-session skills-based VR-delivered therapy was constructed with daily brief exposures to pain coping skills experiences to improve self-regulation and long-term skills acquisition that could be applied in daily life after they had completed the therapy and returned the VR headset. Although the 56-session, fixed-sequence VR delivered-therapy was designed to build the skills and habits needed to mitigate and cope with chronic pain. Clearly this “one size fits all” approach can be improved upon in this era of precision medicine. This is briefly discussed in the Future Directions.

A “pivotal” RCT was launched in 2020 whose data would be used to support a De Novo submission to the FDA (ClinicalTrials.gov NCT04415177). A total of 188 community-based cLBP individuals were consented and randomized 1:1 to either the 56-session skills-based VR program for cLBP (at the time referred to as EaseVRx) or 56-session Sham VR program that included 2D nature content (Garcia et al., 2021a; Garcia LM. et al., 2021). Both groups received an identical VR headset that was delivered directly to their home. Across both groups, each session ranged in duration from 2-15 min with an average of 6 min per session. Figure 5 summarizes the 56-session sequential structure of the RelieVRx program. Also shown is the Pico G2 4K VR device and patented breathing shield. The study protocol proposed to follow participants from pre-treatment baseline to 6 months post-treatment.

Detailed descriptions of the statistical tests as well as patient-reported outcome measures for Sham VR are presented in the original published manuscript. Here we focus our discussion only on the VR-delivered therapy. Pain intensity and pain interference decreased significantly over the course of the 56-session intervention, and this reduction was statistically larger for the VR-delivered therapy group than for the Sham VR group. Baseline pain intensity and the four pain interference measures were moderate, ranging from 4.5 to 5.3 on a 0–10-point scale. Across all five primary endpoints, clinically meaningful 2+-point reductions were observed at end-of-treatment, with a 2.2-point average reduction in pain intensity, and a 2.6-, 2.5-, 2.5-, and 2.5-point average reduction in pain interference with activity, sleep, mood and stress, respectively (Farrar et al., 2001). The pain intensity and composite pain interference reductions for the 56-session VR-delivered therapy are presented in Table 3. Engagement with the VR-delivered therapy was strong with participants completing an average of 43.3 of the 56 experiences. The System Usability Scale (Brooke, 1996) was also collected and the VR device obtained an average rating of 84.3 on a 0–100 point scale that represents an A+ system usability rating. The device was also safe and tolerable. Although 9.7% of participants reported at least one episode of nausea or motion sickness, in all cases the condition resolved quickly, and no serious adverse events were reported.

To test the durability of pain intensity and pain interference reductions, participants were asked to report their pain levels at 1-, 2-, and 3-month post-treatment (Garcia et al., 2021c) and at 6-month post-treatment (Garcia et al., 2022). The 6-month post-treatment results were promising (see Table 3) so the study protocol was modified to include 18-month post-treatment (Maddox et al., 2022), and 24-month post-treatment surveys (Maddox et al., 2023c). At 24-month post-treatment, the pain intensity reduction was 1.2 points, and the composite pain interference reduction was 2.0 points for the VR-delivered therapy (see Table 3), and both were statistically larger than for Sham VR, suggesting that the VR-delivered therapy was providing the necessary long-term skill development that patients needed to manage their pain. The next goal was to utilize these data in an FDA De Novo Authorization application.

The large sample size in the RelieVRx group facilitated several important sub-group analyses. Importantly, many of these sub-group analyses were motivated from discussion with payors, CMS, and healthcare professionals. Two separate sub-group analyses focused on Amtmann et al., 2019 high impact chronic pain and (Dowell et al., 2022) sociodemographic factors are published (Maddox et al., 2024b; Maddox et al., 2025). Detailed statistical analyses can be found in the original publications. Three additional distinct sub-group analyses focused on Amtmann et al., 2019 pain catastrophizing (Dowell et al., 2022), rural/urban setting, and (Singh et al., 2019) duration of cLBP are currently exploratory and await detailed statistical analyses (e.g., MMRM). We briefly review the findings from all 5 sub-group analyses.

Independent investigator research that explores “off-label” uses of RelieVRx are valuable. Several independent investigator studies are ongoing, but to date, four have been completed as described below.

One study examined the effectiveness of RelieVRx combined with telehealth and goal setting in veterans with chronic pain who live in rural areas (VA Diffusion Marketplace, 2025). 20 rural Veterans with chronic pain participated and provided pre-treatment surveys, completed 56 daily sessions with RelieVRx, and provided post-treatment surveys including pain intensity, pain interference with enjoyment of life, general activity, mood, as well as sleep disturbance, opioid use and PT participation. Results showed that Veterans completed on average 5 RelieVRx sessions per week. Clinically meaningful reductions in pain intensity, pain interference and sleep disturbance were observed. No increase in opioid use was observed, and participation in physical therapy increased from 50% to 93%. These findings suggest that in-home use of RelieVRx combined with telehealth and goal setting may provide a powerful therapy for Veterans living in isolated rural settings.

A second study examined the effectiveness of RelieVRx therapy on opioid craving and several measures of pain in chronic pain participants enrolled in a methadone maintenance program (ClinicalTrials, 2025; Perez, 2023). Fourteen participants with chronic pain and Opioid Use Disorder (OUD) were randomized (ClinicalTrials, 2025; Perez, 2023) to RelieVRx (N = 8) or Sham (N = 6) and completed two onsite sessions per week (2 VR experiences per session) across 6 weeks (24 VR experiences max; not the full 56-session RelieVRx therapy) at an Opioid Treatment Program (OTP). RelieVRx reduced opioid craving and several measures of pain at end-of-treatment relative to baseline while also increasing pain acceptance at end-of-treatment relative to baseline). Importantly, these data served as pilot data for a recently funded $3.7 million NIH grant to explore the impact of the full 56-session RelieVRx program on OUD and chronic pain management.

A third study examined the effectiveness of RelieVRx for pain self-management at home following orthopedic injury (Mace et al., 2024). Ten adults from a Level 1 Trauma Clinic within the Mass General Brigham healthcare system with a recent (≤2 months), isolated orthopedic injury who were at risk for persistent pain and functional limitations were recruited. All participants provided pre-treatment surveys, completed 56 daily sessions with RelieVRx, and provided pos-treatment surveys including measures of pain intensity, interference, catastrophizing, anxiety, depression, sleep, physical function, mindfulness, and self-efficacy. Nine of 10 patients completed all 56-sessions. RelieVRx led to statistically significant improvements in all patient reported outcomes. These data suggest that RelieVRx may be effective at treating acute pain and may reduce the prevalence of acute pain evolving into chronic pain.

Finally, a fourth study examined the efficacy of 10 sessions from the RelieVRx therapy compared to the same therapy delivered as audio-only content using a 5-week randomized crossover design in 54 patients with chronic pain due to temporomandibular disorders (Colloca et al., 2025). Immersive VR-delivered therapy significantly reduced pain intensity, anxiety, and pain interference while improving mood and sleep quality. This study provides strong methodological support for the importance of the immersive quality of VR-delivered therapy in managing chronic pain.

AppliedVR followed several parallel tracks toward commercialization and reimbursement of RelieVRx. These included launching several commercial payor pilots with national payors, regional health plans, national managed care organizations, and workers’ compensation carriers. Commercial payor pilots allow for validation and demonstration of the product’s effectiveness in real-world settings. This can lead to broader payor coverage and reimbursement opportunities, build trust with insurance companies, drive market adoption, attract other potential users to the product, and position the company and product as leaders in innovative solutions, increasing its credibility in the healthcare sector. As of publication of this manuscript, several commercial pilots have been completed, and several others are underway. This real-world evidence generation has been key when conducting value analyses which is often necessary to secure positive coverage policies.

Commercialization efforts also included direct engagement in target markets. The company was successful in obtaining a 1-year VA Innovation ecosystem award in December 2022 that was extended to a second year of support and treated 750 Veterans across the country with RelieVRx. In parallel there was an expansion of access to RelieVRx in the VA through the VA Federal Supply Schedule (FSS) starting in 2023. As of publication of this manuscript, nearly half of the VA Medical Centers across the country have prescribed RelieVRx, and thousands of Veterans have obtained relief for their chronic pain with RelieVRx.

The path toward reimbursement is best understood as a combination of coding, benefit category and payment, and coverage. At present, many VR-specific healthcare services are not reimbursed by CMS or other insurance payors. In April 2023, and following extensive interaction with CMS, CMS created a VR-specific billing code–HCPCS code E1905 – for RelieVRx (Centers for Med icare and Medicaid Services, 2022). A payment rate was subsequently published in October 2023 (Centers for Med icare and Medicaid Services, 2022). The specifics of how this process unfolded are instructive and are briefly summarized below (for details see Oldstone and Judge (2024)).

Regulatory strategy is central to the path toward reimbursement. Because RelieVRx is SiMD and is FDA-Authorized for in-home use independent of clinician involvement, it fits best in the existing CMS benefit category of durable medical equipment (DME). The function of any piece of DME is best represented by its CMS Healthcare Common Procedure Coding System (HCPCS) code. At the time of FDA-Authorization for RelieVRx, an appropriate HCPCS code did not exist so AppliedVR petitioned CMS to create a new HCPCS code, and this request was granted with the establishment of the new HCPCS Level II code E1905, “Virtual reality cognitive behavioral therapy device (CBT), including pre-programmed therapy software” to describe RelieVRx. While AppliedVR initiated the application that led to this code, it can potentially apply to other VR-delivered therapies meeting its criteria.

This coding decision positioned the RelieVRx program as the first immersive or digital therapeutic to be integrated into an existing benefit category, offering a clear path to Medicare coverage eligibility, thereby influencing wider commercial coverage. The final step in the HCPCS process is determination of the payment rate (for details see Oldstone and Judge (2024)). In October 2023, RelieVRx E1905 was classified by CMS as a 13-month rental DME item with established monthly rental rates. The full course of therapy typically requires a 3-month episode of care with the total expected reimbursement for the standard treatment duration to be at $1,888.98, based on CMS’s published fee schedule.

Coverage relies on the product or service being deemed “reasonable and necessary” for each patient, once the code, benefit category, and payment rate are determined. This may be determined on a case-by-case basis by either the Medicare Administrative Contractors (MACs) or the insurance company’s medical team for new products, like RelieVRx. Coverage policy can be written over time to clearly define the conditions for coverage. This may include diagnostic or procedure codes or specific patient characteristics that must be documented for the technology to be covered and paid for.

Commercial coverage of RelieVRx continues to expand. AppliedVR strategically introduced RelieVRx into the workers’ compensation sector in July 2023, aiming to provide injured workers with a non-pharmacologic pain management option. Also in May 2024, Highmark BCBS, a Pittsburgh-based health insurer, became the first commercial payor to cover RelieVRx, extending access to over four million members.

AppliedVR is a traditional, vertically integrated DME, serving as both manufacturer and distributor of RelieVRx to patients’ homes. A typical episode of care lasts 3 months with RelieVRx following a “rent and return” model. Figure 7 summarizes the flow of the patient’s experience. The healthcare professional prescribes RelieVRx to the patient and the device is shipped directly to the patient’s home along with easy-to-follow instructions. The shipping contents are displayed in Figure 8. Once the device is received, the patient can begin the therapy or wait for a member of the patient services team to contact the patient to help set up the device and answer any questions. Although wi-fi connectivity is not required, it is encouraged as it allows the patient services team to track engagement with the device and to use this information to guide periodic check-ins to facilitate therapeutic engagement. Patients receive automated email and text messages at specific times throughout their treatment to encourage and maintain usage. Once the episode of treatment is complete, the device can be placed in the initial shipping box along with the included prepaid shipping label and can be dropped off (free of charge) at a local FedEx facility, or a pickup can be scheduled. Patients have several methods of contacting the patient services team (phone, text, email) should any problems arise with the device or if any questions need to be addressed.

A primary goal at AppliedVR is wider adoption and insurance coverage for RelieVRx. As VR-delivered therapy gains recognition as a cost-effective adjunctive and/or alternative to opioids and traditional treatments for cLBP, more healthcare providers and insurers will support its use. Another goal is to expand RelieVRx’s label beyond cLBP to other pain conditions, and to expand the label to other indications such as anxiety, depression and stress disorders to name a few. All of this will involve extensive engagement with the FDA.

Future advances in healthcare for immersive technology, like VR, are more difficult to predict. Even so, many current trends are suggestive. One major trend is going to be toward personalized, precision healthcare. One simple step toward personalization would be to offer an on-demand, library-based version of RelieVRx after the patient has completed the RelieVRx therapy. Individual differences in skills development and skill decay are well established. By offering an on-demand, library of content to patients following therapy, patients in need of additions skills training could receive that and periodic boosters could be initiated by the patient to mitigate skills-based decay. Of course, more sophisticated personalization is also likely that will involve AI-driven adaptive therapy, where machine learning algorithms analyze patient responses in real time, adjusting VR content, difficulty levels, and therapeutic exercises to maximize effectiveness. The breathing-based algorithms in RelieVRx are a step in this direction, but applications will be much more sophisticated soon.

Biometrics will also be leveraged. Biofeedback integration will become more sophisticated, utilizing wearable sensors to track physiological indicators like heart rate, muscle tension, and breathing patterns. Advanced biofeedback will allow patients to interact with therapy in real time, reinforcing relaxation and pain management techniques more effectively. In the early Samsung Gear VR days, AppliedVR explored integration of heart rate into the therapy, but the technical hurdles were too great. Those hurdles will be much smaller and the value-add much larger soon.

Experiences will also become multisensory and may incorporate haptic feedback, temperature control, and even scent-based stimulation to create deeply immersive environments that enhance relaxation and cognitive distraction from pain. Hybrid therapies that include VR-delivered therapies like RelieVRx that are combined with social experiences that allow group support and social interactions designed to address isolation and leverage group therapy dynamics will be explored. Although an exciting avenue for the future, FDA-authorization in precision medicine is going to require rethinking on the regulatory front as the current approaches focus on one-size-fits-all therapies that are easier to validate empirically.

There are several limitations to consider when evaluating the empirical data summarized in this article. First and foremost, one must always objectively evaluate the quality of the control condition used in any randomized controlled trial. Both randomized controlled trials summarized here used an active Sham VR control that displayed 2D nature scenes. Although on the surface this control appears strong, unintended placebo effects and issues of blinding are always possible (for an excellent discussion of VR control group selection see (Persky and Colloca, 2023). Second, the sample size for the initial randomized controlled trial was relatively small, as were the sample sizes for all the studies conducted on the first product line. Third, cLBP was self-reported and was not confirmed by healthcare professionals. Finally, more informative experimental designs and other indications were not explored.