Virtual reality (VR) therapy for patients with psychosis: satisfaction and side effects.

BACKGROUND: Automated virtual reality therapies are being developed to increase access to psychological interventions. We assessed the experience with one such therapy of patients diagnosed with psychosis, including satisfaction, side effects, and positive experiences of access to the technology. We tested whether side effects affected therapy. METHODS: In a clinical trial 122 patients diagnosed with psychosis completed baseline measures of psychiatric symptoms, received gameChange VR therapy, and then completed a satisfaction questionnaire, the Oxford-VR Side Effects Checklist, and outcome measures. RESULTS: 79 (65.8%) patients were very satisfied with VR therapy, 37 (30.8%) were mostly satisfied, 3 (2.5%) were indifferent/mildly dissatisfied, and 1 (0.8%) person was quite dissatisfied. The most common side effects were: difficulties concentrating because of thinking about what might be happening in the room (n = 17, 14.2%); lasting headache (n = 10, 8.3%); and the headset causing feelings of panic (n = 9, 7.4%). Side effects formed three factors: difficulties concentrating when wearing a headset, feelings of panic using VR, and worries following VR. The occurrence of side effects was not associated with number of VR sessions, therapy outcomes, or psychiatric symptoms. Difficulties concentrating in VR were associated with slightly lower satisfaction. VR therapy provision and engagement made patients feel: proud (n = 99, 81.8%); valued (n = 97, 80.2%); and optimistic (n = 96, 79.3%). CONCLUSIONS: Patients with psychosis were generally very positive towards the VR therapy, valued having the opportunity to try the technology, and experienced few adverse effects. Side effects did not significantly impact VR therapy. Patient experience of VR is likely to facilitate widespread adoption.

Agoraphobic avoidance in patients with psychosis: Severity and response to automated VR therapy in a secondary analysis of a randomised controlled clinical trial.

BACKGROUND: The social withdrawal of many patients with psychosis can be conceptualised as agoraphobic avoidance due to a range of long-standing fears. We hypothesised that greater severity of agoraphobic avoidance is associated with higher levels of psychiatric symptoms and lower levels of quality of life. We also hypothesised that patients with severe agoraphobic avoidance would experience a range of benefits from an automated virtual reality (VR) therapy that allows them to practise everyday anxiety-provoking situations in simulated environments. METHODS: 345 patients with psychosis in a randomised controlled trial were categorised into average, moderate, high, and severe avoidance groups using the Oxford Agoraphobic Avoidance Scale. Associations of agoraphobia severity with symptom and functioning variables, and response over six months to brief automated VR therapy (gameChange), were tested. RESULTS: Greater severity of agoraphobic avoidance was associated with higher levels of persecutory ideation, auditory hallucinations, depression, hopelessness, and threat cognitions, and lower levels of meaningful activity, quality of life, and perceptions of recovery. Patients with severe agoraphobia showed the greatest benefits with gameChange VR therapy, with significant improvements at end of treatment in agoraphobic avoidance, agoraphobic distress, ideas of reference, persecutory ideation, paranoia worries, recovering quality of life, and perceived recovery, but no significant improvements in depression, suicidal ideation, or health-related quality of life. CONCLUSIONS: Patients with psychosis with severe agoraphobic avoidance, such as being unable to leave the home, have high clinical need. Automated VR therapy can deliver clinical improvement in agoraphobia for these patients, leading to a number of wider benefits.

Estimating the Economic Value of Automated Virtual Reality Cognitive Therapy for Treating Agoraphobic Avoidance in Patients With Psychosis: Findings From the gameChange Randomized Controlled Clinical Trial.

BACKGROUND: An automated virtual reality cognitive therapy (gameChange) has demonstrated its effectiveness to treat agoraphobia in patients with psychosis, especially for high or severe anxious avoidance. Its economic value to the health care system is not yet established. OBJECTIVE: In this study, we aimed to estimate the potential economic value of gameChange for the UK National Health Service (NHS) and establish the maximum cost-effective price per patient. METHODS: Using data from a randomized controlled trial with 346 patients with psychosis (ISRCTN17308399), we estimated differences in health-related quality of life, health and social care costs, and wider societal costs for patients receiving virtual reality therapy in addition to treatment as usual compared with treatment as usual alone. The maximum cost-effective prices of gameChange were calculated based on UK cost-effectiveness thresholds. The sensitivity of the results to analytical assumptions was tested. RESULTS: Patients allocated to gameChange reported higher quality-adjusted life years (0.008 QALYs, 95% CI -0.010 to 0.026) and lower NHS and social care costs (-£105, 95% CI -£1135 to £924) compared with treatment as usual (£1=US $1.28); however, these differences were not statistically significant. gameChange was estimated to be worth up to £341 per patient from an NHS and social care (NHS and personal social services) perspective or £1967 per patient from a wider societal perspective. In patients with high or severe anxious avoidance, maximum cost-effective prices rose to £877 and £3073 per patient from an NHS and personal social services perspective and societal perspective, respectively. CONCLUSIONS: gameChange is a promising, cost-effective intervention for the UK NHS and is particularly valuable for patients with high or severe anxious avoidance. This presents an opportunity to expand cost-effective psychological treatment coverage for a population with significant health needs. TRIAL REGISTRATION: ISRCTN Registry ISRCTN17308399; https://www.isrctn.com/ISRCTN17308399. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-031606.

Automated virtual reality therapy to treat agoraphobic avoidance and distress in patients with psychosis (gameChange): a multicentre, parallel-group, single-blind, randomised, controlled trial in England with mediation and moderation analyses.

BACKGROUND: Automated delivery of psychological therapy using immersive technologies such as virtual reality (VR) might greatly increase the availability of effective help for patients. We aimed to evaluate the efficacy of an automated VR cognitive therapy (gameChange) to treat avoidance and distress in patients with psychosis, and to analyse how and in whom it might work. METHODS: We did a parallel-group, single-blind, randomised, controlled trial across nine National Health Service trusts in England. Eligible patients were aged 16 years or older, with a clinical diagnosis of a schizophrenia spectrum disorder or an affective diagnosis with psychotic symptoms, and had self-reported difficulties going outside due to anxiety. Patients were randomly assigned (1:1) to either gameChange VR therapy plus usual care or usual care alone, using a permuted blocks algorithm with randomly varying block size, stratified by study site and service type. gameChange VR therapy was provided in approximately six sessions over 6 weeks. Trial assessors were masked to group allocation. Outcomes were assessed at 0, 6 (primary endpoint), and 26 weeks after randomisation. The primary outcome was avoidance of, and distress in, everyday situations, assessed using the self-reported Oxford Agoraphobic Avoidance Scale (O-AS). Outcome analyses were done in the intention-to-treat population (ie, all participants who were assigned to a study group for whom data were available). We performed planned mediation and moderation analyses to test the effects of gameChange VR therapy when added to usual care. This trial is registered with the ISRCTN registry, 17308399. FINDINGS: Between July 25, 2019, and May 7, 2021 (with a pause in recruitment from March 16, 2020, to Sept 14, 2020, due to COVID-19 pandemic restrictions), 551 patients were assessed for eligibility and 346 were enrolled. 231 (67%) patients were men and 111 (32%) were women, 294 (85%) were White, and the mean age was 37·2 years (SD 12·5). 174 patients were randomly assigned to the gameChange VR therapy group and 172 to the usual care alone group. Compared with the usual care alone group, the gameChange VR therapy group had significant reductions in agoraphobic avoidance (O-AS adjusted mean difference -0·47, 95% CI -0·88 to -0·06; n=320; Cohen's d -0·18; p=0·026) and distress (-4·33, -7·78 to -0·87; n=322; -0·26; p=0·014) at 6 weeks. Reductions in threat cognitions and within-situation defence behaviours mediated treatment outcomes. The greater the severity of anxious fears and avoidance, the greater the treatment benefits. There was no significant difference in the occurrence of serious adverse events between the gameChange VR therapy group (12 events in nine patients) and the usual care alone group (eight events in seven patients; p=0·37). INTERPRETATION: Automated VR therapy led to significant reductions in anxious avoidance of, and distress in, everyday situations compared with usual care alone. The mediation analysis indicated that the VR therapy worked in accordance with the cognitive model by reducing anxious thoughts and associated protective behaviours. The moderation analysis indicated that the VR therapy particularly benefited patients with severe agoraphobic avoidance, such as not being able to leave the home unaccompanied. gameChange VR therapy has the potential to increase the provision of effective psychological therapy for psychosis, particularly for patients who find it difficult to leave their home, visit local amenities, or use public transport. FUNDING: National Institute of Health Research Invention for Innovation programme, National Institute of Health Research Oxford Health Biomedical Research Centre.

Understanding agoraphobic avoidance: the development of the Oxford Cognitions and Defences Questionnaire (O-CDQ).

BACKGROUND: Many patients with mental health disorders become increasingly isolated at home due to anxiety about going outside. A cognitive perspective on this difficulty is that threat cognitions lead to the safety-seeking behavioural response of agoraphobic avoidance. AIMS: We sought to develop a brief questionnaire, suitable for research and clinical practice, to assess a wide range of cognitions likely to lead to agoraphobic avoidance. We also included two additional subscales assessing two types of safety-seeking defensive responses: anxious avoidance and within-situation safety behaviours. METHOD: 198 patients with psychosis and agoraphobic avoidance and 1947 non-clinical individuals completed the item pool and measures of agoraphobic avoidance, generalised anxiety, social anxiety, depression and paranoia. Factor analyses were used to derive the Oxford Cognitions and Defences Questionnaire (O-CDQ). RESULTS: The O-CDQ consists of three subscales: threat cognitions (14 items), anxious avoidance (11 items), and within-situation safety behaviours (8 items). Separate confirmatory factor analyses demonstrated a good model fit for all subscales. The cognitions subscale was significantly associated with agoraphobic avoidance (r = .672, p < .001), social anxiety (r = .617, p < .001), generalized anxiety (r = .746, p < .001), depression (r = .619, p < .001) and paranoia (r = .655, p < .001). Additionally, both the O-CDQ avoidance (r = .867, p < .001) and within-situation safety behaviours (r = .757, p < .001) subscales were highly correlated with agoraphobic avoidance. The O-CDQ demonstrated excellent internal consistency (cognitions Cronbach's alpha = .93, avoidance Cronbach's alpha = .94, within-situation Cronbach's alpha = .93) and test-re-test reliability (cognitions ICC = 0.88, avoidance ICC = 0.92, within-situation ICC = 0.89). CONCLUSIONS: The O-CDQ, consisting of three separate scales, has excellent psychometric properties and may prove a helpful tool for understanding agoraphobic avoidance across mental health disorders.

Z Factor: Drama as a tool to tackle mental health stigma: study design and protocol for community and public engagement in rural Zimbabwe.

Background: Mental health is slowly gaining global significance as a key health issue, yet the stigma attached to psychosis is still a major problem. There has been little in-depth exploration of sustainable, cost-effective, and replicable community engagement strategies that address mental health myths and stigma, which are major barriers to early health-seeking behaviours. In low-income countries such as Zimbabwe, cultural and spiritual beliefs are at the centre of most mental health explanatory models, perpetuating an environment where mental health conversations are a cultural taboo. Mental health interventions should be accompanied by creative, evidence-based community engagement, ensuring that interventions are suitable for local settings and giving communities a voice in directing their health initiatives.  Methods: Z Factor aimed to engage young adults and their support networks across a variety of socioeconomic groups in a rural district of Zimbabwe through their participation in an inter-ward five-staged drama competition. The focus was on psychosis, with subcategories of initial presentation/detection, seeking help/pathway to care, and the road to recovery/treatment. Each drama group's composition included a young adult and a typical support network seeking treatment from the service provider of choice. Dramas were to act as discussion starters, paving the way toward broader and deeper psychosis treatment discussions among rural communities and gaining insight into service user expectations from health research. Conclusions: Outcomes of the pilot community engagement project will be instrumental in improving understanding community perceptions about psychosis treatment and recovery in rural Zimbabwe and increasing community awareness about psychosis, as well as paving the way for initiating service provider collaboration to promote early detection and encouraging early health-seeking behaviours. The above outcomes will also inform the design of models for more responsive community and public engagement initiatives in similar low resource settings in Zimbabwe and beyond.

Automated virtual reality (VR) cognitive therapy for patients with psychosis: study protocol for a single-blind parallel group randomised controlled trial (gameChange).

INTRODUCTION: Many patients with psychosis experience everyday social situations as anxiety-provoking. The fears can arise, for example, from paranoia, hallucinations, social anxiety or negative-self beliefs. The fears lead patients to withdraw from activities, and this isolation leads to a cycle of worsening physical and mental health. Breaking this cycle requires highly active treatment directly in the troubling situations so that patients learn that they can safely and confidently enter them. However patients with psychosis seldom receive such life-changing interventions. To solve this problem we have developed an automated psychological treatment delivered in virtual reality (VR). It allows patients to experience computer simulations of the situations that they find anxiety-provoking. A virtual coach guides patients, using cognitive techniques, in how to overcome their fears. Patients are willing to enter VR simulations of anxiety-provoking situations because they know the simulations are not real, but the learning made transfers to the real world. METHODS AND ANALYSIS: 432 patients with psychosis and anxious avoidance of social situations will be recruited from National Health Service (NHS) secondary care services. In the gameChange trial, they will be randomised (1:1) to the six-session VR cognitive treatment added to treatment as usual or treatment as usual alone. Assessments will be conducted at 0, 6 (post-treatment) and 26 weeks by a researcher blind to allocation. The primary outcome is avoidance and distress in real-life situations, using a behavioural assessment task, at 6 weeks. The secondary outcomes are psychiatric symptoms, activity levels and quality of life. All main analyses will be intention-to-treat. Moderation and mediation will be tested. An economic evaluation will be conducted. ETHICS AND DISSEMINATION: The trial has received ethical approval from the NHS South Central - Oxford B Research Ethics Committee (19/SC/0075). A key output will be a high-quality automated VR treatment for patients to overcome anxious avoidance of social situations. TRIAL REGISTRATION NUMBER: ISRCTN17308399.

Alpha-gamma interactions are disturbed in schizophrenia: a fusion of electroencephalography and functional magnetic resonance imaging.

OBJECTIVE: To delineate regional brain activity associated with the alpha oscillations related to perception of sensory stimuli, and test the hypothesis that the synchronisation of alpha oscillations with stimulus onset is impaired in schizophrenia. METHODS: Joint independent component analysis was applied to electroencephalographic and functional magnetic resonance imaging data recorded in 19 individuals with schizophrenia and 19 healthy individuals during a vibrotactile somatosensory task. RESULTS: In healthy individuals the strongest component was dominated by alpha oscillations, and was associated not only with activity in somatosensory regions but also in the insula and anterior cingulate cortex (the salience network). In schizophrenia, the strongest component had low alpha power and activity was limited mainly to somatosensory regions. Furthermore, in the healthy group, but not the patients, significant correlation was observed between the strongest component and evoked gamma power. CONCLUSION: The correlation between the alpha-dominated component and evoked gamma power is consistent with the hypothesis that gamma localised to sensory cortex elicits stimulus-locking of spatially distinct, large-scale ongoing alpha oscillations. Furthermore, this hypothesised mechanism appears to be disrupted in schizophrenia. SIGNIFICANCE: These findings suggest that a weakened alpha-gamma interaction underlies impaired recruitment of the brain during sensory information processing in schizophrenia.

Evidence for reduced somatosensory lateralisation and focalisation in schizophrenia.

Neuroimaging studies indicate diminished lateralisation of cerebral activity during motor tasks and language processing in schizophrenia. Some evidence also indicates that decreased lateralisation is accompanied by more diffuse intra-hemispheric activation, suggesting that diminished lateralisation might be part of a more general diminution of regional functional specialisation. In the case of passive processing of elementary somatosensory stimuli, evidence for decreased lateralisation derived from event-related potential studies, is conflicting. The greater spatial resolution of functional magnetic resonance imaging (fMRI) offers the potential to resolve this conflict. We report an fMRI study of 22 right-handed individuals with schizophrenia, 21 right-handed healthy individuals and 10 non-right-handed healthy individuals, designed to test the hypothesis that in schizophrenia there is a diminution of both lateralisation and intra-hemispheric focalisation during the passive processing of vibrotactile stimuli delivered to the right index finger. Significantly reduced lateralisation of activity in primary somatosensory cortex (SI) was observed in the schizophrenia group as compared to the healthy right-handed group. There was a trend for a reduction in SI lateralisation in the schizophrenia group compared to the healthy non-right-handed group. Contralateral SI focalisation was also significantly reduced in the schizophrenia group compared to both healthy groups. SI focalisation was negatively correlated with severity of disorganisation symptoms in the schizophrenia group. These results support the hypothesis that a generalised loss of functional specialisation is fundamental to schizophrenia.