Background: Many patients suffering from schizophrenia spectrum disorders continue having distressing auditory hallucinations in spite of treatment with antipsychotic medication. The aim of this trial is to examine the effect of a targeted virtual reality therapy for persistent auditory hallucinations in individuals with psychosis. The trial explores whether this type of therapy can decrease the severity, frequency and distress of auditory hallucinations and, additionally, whether it can reduce clinical symptoms and enhance daily functioning in individuals with psychosis. Methods: The study is a randomised, assessor-blinded parallel-group superiority clinical trial, allocating a total of 266 patients to either the experimental intervention or supportive counselling. The participants will be randomised to either (1) seven sessions of virtual reality therapy or (2) seven sessions of supportive counselling to be delivered within the first 12 weeks after inclusion in the study. All participants will be assessed at baseline and 12 and 24 weeks post-baseline. Independent assessors blinded to the treatment allocation will evaluate the outcome. The primary outcome is the level of auditory hallucinations measured with the Psychotic Symptoms Rating Scales (PSYRATS-AH) total score at the cessation of treatment at 12 weeks. Secondary outcomes are frequency of auditory hallucinations, the distress caused by auditory hallucinations, perceived voice power, patient acceptance of voices, patients’ ability to respond to voices in an assertive way and social and daily function. Discussion: Promising evidence of the efficacy of this immersive virtual reality-based therapy for auditory hallucinations exist, but evidence needs to be established in a large, methodological rigorous trial. If the therapy proves to be beneficial in reducing the severity of refractory auditory hallucinations, a large group of patients with schizophrenia and related disorders could be the target group of this short-term psychotherapeutic intervention.

A large group of psychiatric patients suffer from auditory hallucinations (AH) despite relevant treatment regimens. In mental health populations, AH tend to be verbal (AVH) and the content critical or abusive. Trials employing immersive virtual reality (VR) to treat mental health disorders are emerging. The aim of this scoping review is to provide an overview of clinical trials utilizing VR in the treatment of AH and to document knowledge gaps in the literature. PubMed, Cochrane Library, and Embase were searched for studies reporting on the use of VR to target AH. 16 papers were included in this PRISMA scoping review (ScR). In most studies VR therapy (VRT) was employed to ameliorate treatment resistant AVH in schizophrenia spectrum disorders. Only two studies included patients with a diagnosis of affective disorders. The VRT was carried out with the use of an avatar to represent the patient's most dominant voice. The research field employing VR to treat AH is promising but still in its infancy. Results from larger randomized clinical trials are needed to establish substantial evidence of therapy effectiveness. Additionally, the knowledge base would benefit from more profound qualitative data exploring views of patients and therapists.

Paranoia is a distressing and prevalent symptom in schizophrenia spectrum disorders. Virtual reality-based cognitive behavioral therapy for paranoia (VR-CBTp) has been proposed to augment behavioral interventions by providing controlled and safe virtual environments in which social situations inducing paranoid anxiety can be manipulated, allowing for new therapeutical possibilities such as gradual exposure and repetition. This assessor-masked, randomized parallel group superiority trial investigated the efficacy of VR-CBTp compared to standard CBTp. Participants were randomized to receive ten sessions of VR-CBTp or CBTp, both on top of treatment as usual. Intention-to-treat analyses included 254 participants (VR-CBTp: n = 126, CBTp: n = 128). Outcomes were assessed at baseline, treatment cessation and follow-up (6 months after treatment cessation). The primary outcome was Ideas of Persecution subscale from the Green Paranoid Thoughts Scale, measured at treatment cessation. There was not a statistically significant between-group difference on the primary outcome at endpoint (effect estimate: 2% in favor of VR-CBTp; 95% confidence interval: −11% to +17%; Cohen’s d = 0.04; P = 0.77, based on exponentiated log-transformed data). No deaths or violent incidents involving law enforcement occurred during the study. In conclusion, VR-CBTp was not superior to CBTp in reducing schizophrenia-spectrum-disorders-related paranoia. ClinicalTrials.gov registration: NCT04902066.

Background: Immersive virtual reality–assisted therapy (VRT) is a relational therapy for distressing voices in psychosis. Like AVATAR therapy (AT), VRT centers on therapist-facilitated dialogues with a digital avatar representing a voice. Unlike AT, VRT uses immersive virtual reality (VR). While participant experiences of AT have been explored, therapist perspectives remain unexamined, and for VRT, neither participant nor therapist experiences have been studied. Understanding these perspectives is essential to inform optimization of therapy, future research, and implementation. Objective: The objective of this qualitative study was to explore both trial participants’ and therapists’ experience of VRT in the Challenge trial. Methods: Semistructured interviews were conducted with 10 trial participants and 8 therapists across the 3 Challenge trial sites. Trial participants were purposively sampled to ensure site representation and variation in voice-hearing duration. Individual interviews were conducted with trial participants, while therapists participated in site-based groups with 2‐3 in each. Interviews were audio-recorded, transcribed, and subjected to reflexive thematic analysis from a critical realist position. Coding and theme development were inductive. People with lived experience were invited to an initial focus group for topic guide development and a later theme validation workshop. Reporting followed the Standards of Reporting Qualitative Research (SRQR). Results: A total of five overarching themes were generated: (1) using technology to meet the voice, (2) a different approach to voice-hearing and treatment, (3) on a tight schedule, (4) a toolbox for transformation, and (5) a price to pay. Trial participants and therapists generally found VRT acceptable, appropriate, and feasible. Highlights included the acknowledging approach to the voice(s), facilitation of engagement with the voice(s), and opportunity to share the otherwise private experience of voice-hearing. Externalizing and embodying the voice(s) in VR-supported avatar role-plays was seen as a key affordance. Positive outcomes included increased trial participant empowerment and self-worth, enabling or improving voice dialogue, new understanding of voice intentions, and changes in voice frequency or content. Challenges included instances of participant anxiety, exhaustion, or suboptimal sense of (voice) presence; adverse voice reactions; technological malfunctions and limitations to avatar design; measurement insensitivity; tensions between assertiveness and compassion; difficulties with reproducing negative voice content; and the demanding nature of the therapy and the nontraditional skills required of therapists. Conclusions: The study provided comprehensive insights into trial participants’ and therapists’ experiences of VRT in the Challenge trial. Findings share several similarities with qualitative research on other relational therapies for distressing voices and highlight VRT’s potential for positive change. Key considerations for future research and implementation include monitoring anxiety and voice reactions, ensuring operational reliability of hardware and software, and addressing the additional effort required by therapists, which may be unsustainable in routine practice. As a demanding intervention, the successful implementation of VRT will require adequate training, supervision, and structural support.

Auditory verbal hallucinations (AVH) are frequent and debilitating symptoms of schizophrenia spectrum disorders (SSD). In the current randomized, assessor-blinded, parallel-group superiority clinical trial, a total of 270 participants, diagnosed with SSD suffering from treatment-resistant AVH, were randomly assigned to seven sessions of either a virtual reality-assisted therapy (Challenge-VRT) or supportive counselling. Assessment of outcome was conducted at baseline, and at 12 and 24 weeks post baseline. Linear mixed model analyses demonstrated that Challenge-VRT significantly reduced the symptom load of AVH on the primary outcome measured with the Psychotic Symptoms Rating Scales (PSYRATS-AH total, adjusted mean difference: -2.26, 95% Cl: -4.26 to -0.25, p = 0.03) and the secondary outcome measure on frequency of AVH (PSYRATS-Frequency, adjusted mean difference: -0.84, 95% Cl: -1.53 to -0.14, p = 0.02) at treatment cessation 12 weeks post baseline. We conclude that the brief Challenge-VRT is a viable new treatment method for reducing the severity of AVH. ClinicalTrials.gov identifier NCT04661163

Background: Auditory verbal hallucinations (voices) are common in schizophrenia spectrum disorders (SSD), and cause significant distress, making them a critical target in psychotherapeutic interventions. AVATAR therapy, conducted on a two-dimensional computer screen and its adaptation virtual reality-assisted therapy (VRT), using three-dimensional virtual reality (VR), have shown promise. Despite the potential of VRT, research exploring how specific VR characteristics can simulate voices experiences and affect therapy outcome remains scarce. Addressing this gap is key to refining VRT for persistent voices. Objective: This qualitative substudy of the CHALLENGE trial explored patient perspectives on modified VRT versions (VRT-Emotions, VRT-Environment, and VRT-Whiteboard) and their therapeutic impact, with the aim to inform intervention refinement and development. Methods: Semistructured interviews were conducted with 15 participants with SSD and persistent voices after undergoing the modified therapies. Data were analyzed within a pragmatist-critical realism orientation, with a hybrid deductive-inductive approach to thematic analysis. Reflexive team dialogues supported analytical rigor. Results: One overarching theme: A challenging yet transformative therapy, and three subthemes, corresponding to the specific modifications, were generated: Emotional connection with voice , Recognizability builds resistance, and The power of the written word. The modifications were generally perceived to enhance therapeutic experience and effectiveness, albeit participants’ perspectives varied and sometimes contrasted. Conclusions: Findings suggest that refining VRT for persistent voices may involve improving avatar's facial expressions, tailoring therapy to voice experiences, and using recognizable VR environments with gradual exposure and selective visual tools. While controlled studies are needed to establish efficacy, these insights offer practical guidance for VRT refinement and development.