---
title: "Efficacy and Safety of Virtual Reality-Based Emotion-to-Emotion Therapy for PTSD"
id: "plos-one-3-virtual-reality-based-emotion-to-emotion-therapy-for-post-traumatic-stress"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-3-virtual-reality-based-emotion-to-emotion-therapy-for-post-traumatic-stress"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593"
published_at: "2026-09-02T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Efficacy and Safety of Virtual Reality-Based Emotion-to-Emotion Therapy for PTSD
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-3-virtual-reality-based-emotion-to-emotion-therapy-for-post-traumatic-stress
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593)
- **Published At:** 2026-09-02T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The study investigates **virtual reality-based Emotion-to-Emotion Therapy (VR-ETE)** for **post-traumatic stress disorder (PTSD)**. - Emotion-to-Emotion Therapy (ETE) aims to regulate emotional responses through opposing emotions, rooted in **traditional Korean medicine**. - The trial involves **72 adults** with PTSD, randomly assigned to VR-ETE, standard ETE, or a waitlist control group. - Participants in both active groups will undergo **16 sessions over 8 weeks**. - Primary outcomes will be assessed via the **PTSD Checklist for DSM-5 (PCL-5-K)** score and various secondary measures at baseline, week 8, and week 12. - The study addresses the gap in research on VR as a platform for delivering psychotherapy. - This protocol emphasizes the need for randomized controlled trials to evaluate the **efficacy**, **safety**, and **cost-effectiveness** of VR-integrated therapies for PTSD.
## Clinical Analysis & Structured Key Points
[ Skip to main content ](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#main-content) Advertisement * [plos.org](https://plos.org/) * [Create account](https://community.plos.org/registration/new) * [Sign in](https://journals.plos.org/user/secure/login?page=%2Fplosone%2Farticle%3Fid%3D10.1371%2Fjournal.pone.0357593) * * About * Browse * Publish * [](https://journals.plos.org/plosone/ "PLOS One") * Search [advanced search](https://journals.plos.org/plosone/search) * [Browse Topics](https://journals.plos.org/plosone/subjectAreaBrowse) Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click [here](https://github.com/PLOS/plos-thesaurus/blob/master/README.md "Link opens in new window"). [](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593) [](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593) * 0 [Save](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357593#savedHeader) [Total Mendeley and Citeulike bookmarks.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357593#savedHeader) * 0 [Citation](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357593#citedHeader) [Paper's citation count computed by Dimensions.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357593#citedHeader) * 52 [View](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357593#viewedHeader) [PLOS views and downloads.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357593#viewedHeader) * 0 [Share](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357593#discussedHeader) [Sum of Facebook, Twitter, Reddit and Wikipedia activity.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357593#discussedHeader) Open Access Study Protocol # Virtual reality-based emotion-to-emotion therapy for post-traumatic stress disorder: Protocol for a randomized controlled trial of efficacy, safety, and cost-effectiveness * Do-Eun Lee, Roles Conceptualization, Investigation, Methodology, Writing – original draft, Writing – review & editing Affiliations Department of Korean Neuropsychiatry Medicine, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea, Korean Medicine Cognitive Disorder Research Center, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-0342-607X ](https://orcid.org/0000-0002-0342-607X "ORCID Registry") ⨯ * Namju Lee, Roles Writing – original draft, Writing – review & editing Affiliation Department of Integrative Medicine, Division of Biomedical and Health Service Convergence, Graduate School of Jeonbuk Advanced Bio-convergence Academy (JABA), Wonkwang University, Iksan, Jeonbuk, Republic of Korea ⨯ * Nam-Kwen Kim, Roles Methodology, Writing – review & editing Affiliation Department of Ophthalmology and Otolaryngology and Dermatology, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0001-6969-1231 ](https://orcid.org/0000-0001-6969-1231 "ORCID Registry") ⨯ * Joohee Seo, Roles Writing – review & editing Affiliation Department of Korean Neuropsychiatry, National Medical Center, Seoul, Republic of Korea ⨯ * Jaeuk U. Kim, Roles Writing – review & editing Affiliation Digital Health Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea ⨯ * In Chul Jung, Roles Conceptualization, Methodology, Writing – review & editing Affiliations Department of Oriental Neuropsychiatry, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea, Clinical Trial Center, Daejeon Korean Medicine Hospital of Daejeon University, Daejeon, Republic of Korea [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0001-7245-4990 ](https://orcid.org/0000-0001-7245-4990 "ORCID Registry") ⨯ * Moon Joo Cheong , Roles Conceptualization, Investigation, Methodology, Supervision, Writing – review & editing * E-mail: sasayayoou@naver.com (MJC); dskhw@wku.ac.kr (HWK) Affiliations Department of Integrative Medicine, Division of Biomedical and Health Service Convergence, Graduate School of Jeonbuk Advanced Bio-convergence Academy (JABA), Wonkwang University, Iksan, Jeonbuk, Republic of Korea, Department of Medical Counseling, College of Health Sciences, Wonkwang University, Iksan, Jeonbuk, Republic of Korea ⨯ * Hyung Won Kang Roles Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – review & editing * E-mail: sasayayoou@naver.com (MJC); dskhw@wku.ac.kr (HWK) Affiliations Department of Korean Neuropsychiatry Medicine, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea, Korean Medicine Cognitive Disorder Research Center, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea, Department of Integrative Medicine, Division of Biomedical and Health Service Convergence, Graduate School of Jeonbuk Advanced Bio-convergence Academy (JABA), Wonkwang University, Iksan, Jeonbuk, Republic of Korea [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0001-6497-0100 ](https://orcid.org/0000-0001-6497-0100 "ORCID Registry") ⨯ # Virtual reality-based emotion-to-emotion therapy for post-traumatic stress disorder: Protocol for a randomized controlled trial of efficacy, safety, and cost-effectiveness * Do-Eun Lee, * Namju Lee, * Nam-Kwen Kim, * Joohee Seo, * Jaeuk U. Kim, * In Chul Jung, * Moon Joo Cheong, * Hyung Won Kang ![PLOS](https://journals.plos.org/resource/img/logo-plos-full-color.svg) x * Published: September 2, 2026 * * [Article](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593) * [Authors](https://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0357593) * [Metrics](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357593) * [Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0357593) * [Media Coverage](http://plos.altmetric.com/details/doi/10.1371/journal.pone.0357593) * [Abstract](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#abstract0) * [Introduction](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#sec004) * [Materials and methods](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#sec005) * [Discussion](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#sec033) * [Dissemination](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#sec034) * [Supporting information](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#sec035) * [References](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#references) * [Reader Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0357593) * [Figures](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593) ## Abstract ### Background Trauma-focused psychotherapies are recommended first-line treatments for post-traumatic stress disorder (PTSD). Emotion-to-Emotion Therapy (ETE) is a psychotherapy derived from traditional Korean medicine that regulates excessive emotional responses using theoretically opposing emotions. Virtual reality (VR) may support standardized and immersive delivery of the meditation component of ETE. This trial will evaluate the efficacy, safety, and cost-effectiveness of VR-based ETE for PTSD. ### Methods This multicenter, randomized, waitlist-controlled, assessor-blinded trial will enroll 72 adults with PTSD and allocate them 1:1:1 to VR-based ETE, standard ETE, or a waitlist control group. Both active groups will receive 16 sessions over 8 weeks; waitlist participants will continue usual activities with scheduled monitoring. The primary endpoint is the between-group difference in the week-8 Korean version of the PTSD Checklist for DSM-5 (PCL-5-K) total score, adjusted for the baseline PCL-5-K score and study site. A week-12 follow-up assessment will examine the durability of treatment effects. Secondary outcomes, assessed at baseline and weeks 8 and 12, include the Core Seven-Emotions Inventory–Short Form, Korean Posttraumatic Growth Inventory, Five Facet Mindfulness Questionnaire–Short Form, Patient Health Questionnaire-15, Hospital Anxiety and Depression Scale, Korean Insomnia Severity Index, Hwa-Byung Scale, Clinical Global Impression scales, quantitative electroencephalography, and heart rate variability. Health-related quality of life and cost data will be collected for a within-trial economic evaluation. ### Discussion This trial will provide preliminary randomized evidence on the efficacy, safety, and cost-effectiveness of standard and VR-based ETE for PTSD, and on whether adding VR to the meditation component of ETE offers clinical value beyond standard ETE. Interpretation will need to consider the modest sample size, the absence of participant blinding, and the use of a waitlist rather than an active control condition. ### Trial registration Clinical Research Information Service of the Republic of Korea, [KCT0007845](https://clinicaltrials.gov/ct2/show/KCT0007845). Registered on October 18, 2022. ## Figures ![Fig 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357593.g001) ![Fig 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357593.g001) ![Fig 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357593.g001) **Citation:** Lee D-E, Lee N, Kim N-K, Seo J, Kim JU, Jung IC, et al. (2026) Virtual reality-based emotion-to-emotion therapy for post-traumatic stress disorder: Protocol for a randomized controlled trial of efficacy, safety, and cost-effectiveness. PLoS One 21(9): e0357593. https://doi.org/10.1371/journal.pone.0357593 **Editor:** Sonu Bhaskar, National Cerebral and Cardiovascular Center: Kokuritsu Junkankibyo Kenkyu Center, JAPAN **Received:** May 11, 2026; **Accepted:** August 18, 2026; **Published:** September 2, 2026 **Copyright:** © 2026 Lee et al. This is an open access article distributed under the terms of the [Creative Commons Attribution License](http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. **Data Availability:** No datasets were generated or analysed for this protocol; data collection is ongoing. Upon completion of the study and publication of the results, the de-identified minimal dataset underlying the reported findings, together with a data dictionary and the analysis code, will be deposited in Figshare ([https://figshare.com)](https://figshare.com) and a persistent identifier will be provided. Access will be subject to applicable participant-consent, ethical, privacy, and legal restrictions. **Funding:** This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI, [https://www.khidi.or.kr)](https://www.khidi.or.kr), funded by the Ministry of Health and Welfare, Republic of Korea (grant no. RS-2021-KH109310) to HWK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. **Competing interests:** The authors have declared that no competing interests exist. ## Introduction Post-traumatic stress disorder (PTSD) is a chronic and potentially disabling psychiatric disorder that develops after exposure to actual or threatened death, serious injury, or sexual violence. It is characterized by intrusive memories, avoidance behaviors, negative alterations in cognition and mood, and hyperarousal, resulting in substantial impairment in daily functioning and health-related quality of life [[1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref001)]. Trauma-focused psychotherapy is recommended as a first-line treatment for PTSD by major international clinical guidelines [[2](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref002)]. Established interventions include cognitive behavioral therapy, cognitive processing therapy, prolonged exposure therapy, narrative exposure therapy, eye movement desensitization and reprocessing, and stress inoculation training [[2](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref002)]. More recently, virtual reality (VR) has emerged as a promising platform for delivering psychological interventions in a standardized, immersive, and reproducible manner [[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref003)]. In patients with PTSD, VR enables controlled therapeutic environments while overcoming several practical limitations of real-world exposure-based interventions, thereby facilitating individualized treatment delivery [[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref003)]. Nevertheless, most existing VR-based interventions have been developed as virtual exposure therapies. To our knowledge, no randomized controlled trial has evaluated a traditional Korean medicine–based psychotherapy integrated with VR for PTSD, highlighting an important gap in the current literature. Traditional Korean medicine adopts a holistic perspective in which mental and physical health are closely interconnected [[4](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref004)]. Within this framework, dysregulated emotional responses are considered important contributors to both psychological and physiological dysfunction [[4](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref004)]. Emotion-to-Emotion Therapy (ETE) is a structured psychotherapeutic approach derived from traditional Korean medicine that seeks to regulate excessive emotional responses by applying theoretically opposing emotions based on the Chiljeong (Seven Emotions) theory [[4](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref004)]. ETE has been incorporated into a Korean medicine–based treatment program for PTSD [[5](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref005)], and a standardized ETE treatment manual has been developed [[6](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref006)]. To our knowledge, no randomized controlled trial has evaluated the efficacy, safety, or cost-effectiveness of ETE for PTSD, either in its conventional format or when integrated with VR. Therefore, the present multicenter randomized controlled trial was designed to compare VR-based ETE, standard ETE, and a waitlist control in adults with PTSD. This protocol describes the study rationale, trial design, interventions, outcome measures, and statistical analysis plan for evaluating the efficacy, safety, and cost-effectiveness of VR-based ETE. ## Materials and methods The original study protocol was prospectively registered with the Clinical Research Information Service of the Republic of Korea (CRIS; registration no. KCT0007845) on October 18, 2022, following Institutional Review Board (IRB) approval and before the initiation of participant recruitment. Subsequent approved amendments, including the multicenter expansion and protocol version 5.1, were approved by the relevant IRBs. The study protocol is presented in accordance with the SPIRIT guidelines [[7](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref007),[8](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.ref008)] ([S1 Checklist](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.s001)). The full study protocol is provided both in the version submitted to the IRB before recruitment began (version 2.0; [S2 File](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.s002), Korean; [S3 File](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.s003), English) and in the current IRB-approved version 5.1 ([S4 File](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.s004), Korean; [S5 File](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone.0357593.s005), English). ### Study design This study is a multicenter, three-arm, parallel-group, randomized, waitlist-controlled, assessor-blinded clinical trial. Seventy-two eligible participants will be randomly allocated in a 1:1:1 ratio to one of three groups: (1) VR-based Emotion-to-Emotion Therapy (VR-ETE), (2) standard Emotion-to-Emotion Therapy (ETE), or (3) a waitlist control group. The overall study design and assessment schedule are presented in [Fig 1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357593#pone-0357593-g001). [![thumbnail](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357593.g001)](https://journals.plos.org/plosone/article/figure/image?size=medium&id=10.1371/journal.pone.0357593.g001 "Click for larger image") Download: * [PNG larger image](https://journals.plos.org/plosone/article/figure/image?download&size=large&id=10.1371/journal.pone.0357593.g001) * [TIFF original image](https://journals.plos.org/plosone/article/figure/image?download&size=original&id=10.1371/journal.pone.0357593.g001) Fig 1. SPIRIT schedule of enrollment, interventions, and assessments. The screening period (−t1) is completed within 7 days before randomization. Mid-intervention assessment (t1) is performed at week 4, post-intervention assessment (t2) at week 8, and follow-up assessment (t3) at week 12. Participants in the two intervention groups attend two treatment sessions per week (16 sessions over 8 weeks). For the intervention groups, the week-4 assessment corresponds to the eighth treatment session, whereas for the waitlist control group it corresponds to the second study visit. Arrows indicate the continuous 16-session intervention period for the two intervention groups. Abbreviations: SCID-5, Structured Clinical Interview for DSM-5; PC-PTSD-5, Primary Care PTSD Screen for DSM-5; ECG, electrocardiogram; ETE, Emotion-to-Emotion Therapy; VR, virtual reality; PCL-5-K, Korean version of the PTSD Checklist for DSM-5; CGI-I, Clinical Global Impression–Improvement scale; K-PTGI, Korean version of the Posttraumatic Growth Inventory; FFMQ-S, Five Facet Mindfulness Questionnaire–Short Form; PHQ-15, Patient Health Questionnaire-15; HADS, Hospital Anxiety and Depression Scale; ISI-K, Korean version of the Insomnia Severity Index; EQ-5D-5L, EuroQol 5-Dimension 5-Level; EQ-VAS, EuroQol visual analogue scale; MRM, Mentalizing the Rooms of Mind; CSEI-S, Core Seven-Emotions Inventory–Short Form; SUDS, Subjective Units of Distress Scale; HRV, heart rate variability; QEEG, quantitative electroencephalography. [ https://doi.org/10.1371/journal.pone.0357593.g001](https://doi.org/10.1371/journal.pone.0357593.g001) ### Patient and public involvement Patients and members of the public were not in
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