An online evidence-based dictionary of common adverse events of antidepressants: a new tool to empower patients and clinicians in their shared decision-making process.

BACKGROUND: Adverse events (AEs) are commonly reported in clinical studies using the Medical Dictionary for Regulatory Activities (MedDRA), an international standard for drug safety monitoring. However, the technical language of MedDRA makes it challenging for patients and clinicians to share understanding and therefore to make shared decisions about medical interventions. In this project, people with lived experience of depression and antidepressant treatment worked with clinicians and researchers to co-design an online dictionary of AEs associated with antidepressants, taking into account its ease of use and applicability to real-world settings. METHODS: Through a pre-defined literature search, we identified MedDRA-coded AEs from randomised controlled trials of antidepressants used in the treatment of depression. In collaboration with the McPin Foundation, four co-design workshops with a lived experience advisory panel (LEAP) and one independent focus group (FG) were conducted to produce user-friendly translations of AE terms. Guiding principles for translation were co-designed with McPin/LEAP members and defined before the finalisation of Clinical Codes (CCs, or non-technical terms to represent specific AE concepts). FG results were thematically analysed using the Framework Method. RESULTS: Starting from 522 trials identified by the search, 736 MedDRA-coded AE terms were translated into 187 CCs, which balanced key factors identified as important to the LEAP and FG (namely, breadth, specificity, generalisability, patient-understandability and acceptability). Work with the LEAP showed that a user-friendly language of AEs should aim to mitigate stigma, acknowledge the multiple levels of comprehension in 'lay' language and balance the need for semantic accuracy with user-friendliness. Guided by these principles, an online dictionary of AEs was co-designed and made freely available ( https://thesymptomglossary.com ). The digital tool was perceived by the LEAP and FG as a resource which could feasibly improve antidepressant treatment by facilitating the accurate, meaningful expression of preferences about potential harms through a shared decision-making process. CONCLUSIONS: This dictionary was developed in English around AEs from antidepressants in depression but it can be adapted to different languages and cultural contexts, and can also become a model for other interventions and disorders (i.e., antipsychotics in schizophrenia). Co-designed digital resources may improve the patient experience by helping to deliver personalised information on potential benefits and harms in an evidence-based, preference-sensitive way.

Aripiprazole/Sertraline Combination: Clinical and Cost-Effectiveness in Comparison With Quetiapine for the Treatment of Bipolar Depression (ASCEnD Trial)-Protocol for a Nested Qualitative Study.

INTRODUCTION: Bipolar disorder is a recurrent mental health disorder with a prevalence rate of 1.4%. On average, there can be a delay of 9.5 years from the initial presentation of symptoms to a confirmed diagnosis. Individuals living with bipolar disorder have a reduced life expectancy. There is limited evidence regarding the effectiveness of antidepressants in treating bipolar disorder. The ASCEnD clinical trial will test the clinical and cost-effectiveness of the aripiprazole/sertraline combination in comparison with quetiapine for the treatment of bipolar depression (individuals who suffer from depressive episodes in bipolar disorder) and will include a nested qualitative study. METHODS: The qualitative study will use semi-structured interviews to explore pilot trial participants' and clinicians' perspectives on recruitment procedures, the acceptability of the intervention, the management of bipolar disorder and attitudes to medication combinations. CONCLUSION: Findings will inform recruitment strategies and optimise training for the participating sites in the ASCEnD full trial. They will also help to illuminate the lived experience of people with bipolar disorder and the clinicians who work with people with bipolar disorder. The discussion will explore perspectives on the delay in diagnosis, having a diagnosis, the impact of living with bipolar disorder and attitudes to treatment, including drug combinations. PATIENT OR PUBLIC CONTRIBUTION: A Lived Experience Advisory Panel (LEAP) has been convened with the support of the McPin Foundation, which will contribute to the ASCEnD trial and its nested qualitative study to provide input on the design and delivery of the trial and qualitative study, analysis of qualitative data and dissemination of findings.

Automated VR therapy for improving positive self-beliefs and psychological well-being in young patients with psychosis: a proof of concept evaluation of Phoenix VR self-confidence therapy.

BACKGROUND: Low self-confidence in patients with psychosis is common. This can lead to higher symptom severity, withdrawal from activities, and low psychological well-being. There are effective psychological techniques to improve positive self-beliefs but these are seldom provided in psychosis services. With young people with lived experience of psychosis we developed a scalable automated VR therapy to enhance positive-self beliefs. AIMS: The aim was to conduct a proof of concept clinical test of whether the new VR self-confidence therapy (Phoenix) may increase positive self-beliefs and psychological well-being. METHOD: Twelve young patients with non-affective psychosis and with low levels of positive self-beliefs participated. Over 6 weeks, patients were provided with a stand-alone VR headset so that they could use Phoenix at home and were offered weekly psychologist meetings. The outcome measures were the Oxford Positive Self Scale (OxPos), Brief Core Schema Scale, and Warwick-Edinburgh Well-being Scale (WEMWBS). Satisfaction, adverse events and side-effects were assessed. RESULTS: Eleven patients provided outcome data. There were very large end-of-treatment improvements in positive self-beliefs (OxPos mean difference = 32.3; 95% CI: 17.3, 47.3; Cohen's d=3.0) and psychological well-being (WEMWBS mean difference = 11.2; 95% CI: 8.0, 14.3; Cohen's d=1.5). Patients rated the quality of the VR therapy as: excellent (n=9), good (n=2), fair (n=0), poor (n=0). An average of 5.3 (SD=1.4) appointments were attended. CONCLUSIONS: Uptake of the VR intervention was high, satisfaction was high, and side-effects extremely few. There were promising indications of large improvements in positive self-beliefs and psychological well-being. A randomized controlled clinical evaluation is warranted.

Cognitive bias modification for paranoia (CBM-pa): a randomised controlled feasibility study in patients with distressing paranoid beliefs.

BACKGROUND: Cognitive Bias Modification for paranoia (CBM-pa) is a novel, theory-driven psychological intervention targeting the biased interpretation of emotional ambiguity associated with paranoia. Study objectives were (i) test the intervention's feasibility, (ii) provide effect size estimates, (iii) assess dose-response and (iv) select primary outcomes for future trials. METHODS: In a double-blind randomised controlled trial, sixty-three outpatients with clinically significant paranoia were randomised to either CBM-pa or an active control (text reading) between April 2016 and September 2017. Patients received one 40 min session per week for 6 weeks. Assessments were given at baseline, after each interim session, post-treatment, and at 1- and 3-months post-treatment. RESULTS: A total of 122 patients were screened and 63 were randomised. The recruitment rate was 51.2%, with few dropouts (four out of 63) and follow-up rates were 90.5% (1-month) and 93.7% (3-months). Each session took 30-40 min to complete. There was no statistical evidence of harmful effects of the intervention. Preliminary data were consistent with efficacy of CBM-pa over text-reading control: patients randomised to the intervention, compared to control patients, reported reduced interpretation bias (d = -0.48 to -0.76), improved symptoms of paranoia (d = -0.19 to -0.38), and lower depressed and anxious mood (d = -0.03 to -0.29). The intervention effect was evident after the third session. CONCLUSIONS: CBM-pa is feasible for patients with paranoia. A fully powered randomised control trial is warranted.

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.

The Oxford Agoraphobic Avoidance Scale.

BACKGROUND: Agoraphobic avoidance of everyday situations is a common feature in many mental health disorders. Avoidance can be due to a variety of fears, including concerns about negative social evaluation, panicking, and harm from others. The result is inactivity and isolation. Behavioural avoidance tasks (BATs) provide an objective assessment of avoidance and in situ anxiety but are challenging to administer and lack standardisation. Our aim was to draw on the principles of BATs to develop a self-report measure of agoraphobia symptoms. METHOD: The scale was developed with 194 patients with agoraphobia in the context of psychosis, 427 individuals in the general population with high levels of agoraphobia, and 1094 individuals with low levels of agoraphobia. Factor analysis, item response theory, and receiver operating characteristic analyses were used. Validity was assessed against a BAT, actigraphy data, and an existing agoraphobia measure. Test-retest reliability was assessed with 264 participants. RESULTS: An eight-item questionnaire with avoidance and distress response scales was developed. The avoidance and distress scales each had an excellent model fit and reliably assessed agoraphobic symptoms across the severity spectrum. All items were highly discriminative (avoidance: a = 1.24-5.43; distress: a = 1.60-5.48), indicating that small increases in agoraphobic symptoms led to a high probability of item endorsement. The scale demonstrated good internal reliability, test-retest reliability, and validity. CONCLUSIONS: The Oxford Agoraphobic Avoidance Scale has excellent psychometric properties. Clinical cut-offs and score ranges are provided. This precise assessment tool may help focus attention on the clinically important problem of agoraphobic avoidance.

Shared goals for mental health research: what, why and when for the 2020s.

Mental health problems bring substantial individual, community and societal costs and the need for innovation to promote good mental health and to prevent and treat mental health problems has never been greater. However, we know that research findings can take up to 20 years to implement. One way to push the pace is to focus researchers and funders on shared, specific goals and targets. We describe a consultation process organised by the Department of Health and Social Care and convened by the Chief Medical Officer to consider high level goals for future research efforts and to begin to identify UK-specific targets to measure research impact. The process took account of new scientific methods and evidence, the UK context with a universal health care system (the NHS) and the embedded research support from the National Institute for Health Research Clinical Research Network, as well as the views of individual service users and service user organisations. The result of the consultation is a set of four overarching goals with the potential to be measured at intervals of three, five or ten years.

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.

Why do patients with psychosis listen to and believe derogatory and threatening voices? 21 reasons given by patients.

BACKGROUND: Around two-thirds of patients with auditory hallucinations experience derogatory and threatening voices (DTVs). Understandably, when these voices are believed then common consequences can be depression, anxiety and suicidal ideation. There is a need for treatment targeted at promoting distance from such voice content. The first step in this treatment development is to understand why patients listen to and believe voices that are appraised as malevolent. AIMS: To learn from patients their reasons for listening to and believing DTVs. METHOD: Theoretical sampling was used to recruit 15 participants with non-affective psychosis from NHS services who heard daily DTVs. Data were obtained by semi-structured interviews and analysed using grounded theory. RESULTS: Six higher-order categories for why patients listen and/or believe voices were theorised. These were: (i) to understand the voices (e.g. what is their motive?); (ii) to be alert to the threat (e.g. prepared for what might happen); (iii) a normal instinct to rely on sensory information; (iv) the voices can be of people they know; (v) the DTVs use strategies (e.g. repetition) to capture attention; and (vi) patients feel so worn down it is hard to resist the voice experience (e.g. too mentally defeated to dismiss comments). In total, 21 reasons were identified, with all participants endorsing multiple reasons. CONCLUSIONS: The study generated a wide range of reasons why patients listen to and believe DTVs. Awareness of these reasons can help clinicians understand the patient experience and also identify targets in psychological intervention.

Supporting movement and physical activity in people with psychosis: A qualitative exploration of the carer perspective.

BACKGROUND: The need to increase exercise and decrease sedentary behaviour in people diagnosed with psychosis is well-recognised. AIMS: We set out to explore caregivers' perspectives on what supports and prevents physical activity, and how to use carers' support most effectively. METHOD: Fourteen caregivers of people diagnosed with psychosis were interviewed. Data were analysed using reflexive thematic analysis, in collaboration with caregivers. RESULTS: Four themes were developed, the first flagging the importance of physical activity, then the others calling for action: (a) Physical inactivity matters: carers are keen to support efforts to increase physical activity in their family or friends because of the enormous impact physical inactivity has on patients, and consequently on carers themselves, such as social isolation and reduction in their own activity. (b) Tell us: without being well-informed about how to help, carers can feel like they are powerless to stop a 'slow suicide' or 'decline' in patients. (c) Listen to us: through knowing their family and friends well, carers are able to identify important changes in patients and identify successful motivators for them, but these insights can feel uninvited. (d) Ask us: being invited to support activity as a partner in a patients' care is desirable but having offers of help rejected can "demotivate the motivator." CONCLUSIONS: Caregivers described strong motivation to help patients to be more physically active but can feel that their support is overlooked and under-used by services. Clinical recommendations for carer involvement in physical activity interventions are offered.

Framework for understanding movement and physical activity in patients diagnosed with psychosis.

BACKGROUND: Patients diagnosed with psychosis often spend less time than others engaged in exercise and more time sitting down, which likely contributes to poorer physical and mental health. OBJECTIVE: The aim of this study was to develop a comprehensive framework from the perspective of patients, carers, and staff for understanding what promotes movement and physical activity. METHODS: A critical realist approach was taken to design the study. Interviews (n=23) and focus groups (n=12) were conducted with (1) outpatients aged 16 years or older diagnosed with psychosis, and under the care of a mental health team, (2) carers and (3) mental health staff working in the community. Purposive sampling was used to maximise variation in participant characteristics. Data were analysed using reflexive thematic analysis. FINDINGS: 19 patients (9 women and 10 men, mean age=45·0 (SD=12·2) years, 15 White British, 2 Black African, 1 Pakistani and 1 other ethnic group), 14 carers (11 women and 3 men, mean age=59·9 (SD=12·7) years, 13 White British and 1 Asian) and 18 staff (14 women and 4 men, mean age=38·7 (SD=12·3) years, 15 White British, 1 White other, 1 Asian Bangladeshi and 1 other Asian) participated in the study. Five factors were found to promote movement and physical activity. Patients must be able to find a purpose to moving which is meaningful to them (Factor 1: Purpose). Patients need to have an expectation of the positive consequences of movement and physical activity, which can be influenced by others' expectations (Factor 2: Predictions). A patient's current physical (eg, pain) and emotional state (eg, distress about voices) needs to be addressed to allow movement and physical activity (Factor 3: Present state). Movement and physical activity can also be encouraged by the availability of effective and tailored support, provided by engaged and supported people (Factor 4: Provision). Finally, through the identification and interruption of vicious cycles (eg, between inactivity and mood states) more positive cycles can be put in place (Factor 5: Process). CONCLUSIONS AND CLINICAL IMPLICATIONS: The 5 P (Purpose, Predictions, Present state, Provision and Process Physical Activity Framework) for understanding movement and physical activity for people diagnosed with psychosis has the potential to inform future research and guide interventions. A checklist is provided for clinicians to help foster change in activity levels.

Developing an Automated Virtual Reality Therapy for Improving Positive Self-Beliefs and Psychological Well-Being (Phoenix VR Self-Confidence Therapy): Tutorial.

Unlabelled: Virtual reality (VR) is an immersive technology in which delivery of psychological therapy techniques can be automated. Techniques can be implemented similarly to real-world delivery or in ways that are not possible in the real world to enhance efficacy. The potential is for greater access for patients to effective therapy. Despite an increase in the use of VR for mental health, there are few descriptions of how to build and design automated VR therapies. We describe the development of Phoenix VR Self-Confidence Therapy, designed to increase positive self-beliefs in young patients diagnosed with psychosis in order to improve psychological well-being. A double-diamond, user-centered design process conducted over the course of 18 months was used, involving stakeholders from multiple areas: individuals with lived experience of psychosis, clinical psychologists, treatment designers, and VR software developers. Thirteen meetings were held with young patients diagnosed with psychosis to increase the understanding and improve the assessment of positive self-beliefs, help design the scenarios for implementing therapeutic techniques, and conduct user testing. The resulting Phoenix therapy is a class I United Kingdom Conformity Assessed (UKCA)-certified medical device designed to be used on the standalone Meta Quest 2 (Meta Platforms) headset. Phoenix aims to build up 3 types of positive self-beliefs that are connected to psychological well-being. In a community farm area, tasks are designed to increase a sense of mastery and achievement ("I can make a difference"); in a TV studio, users complete an activity with graded levels of difficulty to promote success in the face of a challenge ("I can do this"); and in a forest by a lake, activities are designed to encourage feelings of pleasure and enjoyment ("I can enjoy things"). Phoenix is delivered over the course of approximately 6 weekly sessions supported by a mental health provider. Patients can take the headsets home to use in between sessions. Usability testing with individuals with lived experience of psychosis, as well as patients in the National Health Service (aged 16-26 years), demonstrated that Phoenix is engaging, easy to use, and has high levels of satisfaction.

Developing a process for assessing the safety of a digital mental health intervention and gaining regulatory approval: a case study and academic's guide.

BACKGROUND: The field of digital mental health has followed an exponential growth trajectory in recent years. While the evidence base has increased significantly, its adoption within health and care services has been slowed by several challenges, including a lack of knowledge from researchers regarding how to navigate the pathway for mandatory regulatory approval. This paper details the steps that a team must take to achieve the required approvals to carry out a research study using a novel digital mental health intervention. We used a randomised controlled trial of a digital mental health intervention called STOP (Successful Treatment of Paranoia) as a worked example. METHODS: The methods section explains the two main objectives that are required to achieve regulatory approval (MHRA Notification of No Objection) and the detailed steps involved within each, as carried out for the STOP trial. First, the existing safety of digital mental health interventions must be demonstrated. This can refer to literature reviews, any feasibility/pilot safety data, and requires a risk management plan. Second, a detailed plan to further evaluate the safety of the digital mental health intervention is needed. As part of this we describe the STOP study's development of a framework for categorising adverse events and based on this framework, a tool to collect adverse event data. RESULTS: We present literature review results, safety-related feasibility study findings and the full risk management plan for STOP, which addressed 26 possible hazards, and included the 6-point scales developed to quantify the probability and severity of typical risks involved when a psychiatric population receives a digital intervention without the direct support of a therapist. We also present an Adverse Event Category Framework for Digital Therapeutic Devices and the Adverse Events Checklist-which assesses 15 different categories of adverse events-that was constructed from this and used in the STOP trial. CONCLUSIONS: The example shared in this paper serves as a guide for academics and professionals working in the field of digital mental health. It provides insights into the safety assessment requirements of regulatory bodies when a clinical investigation of a digital mental health intervention is proposed. Methods, scales and tools that could easily be adapted for use in other similar research are presented, with the expectation that these will assist other researchers in the field seeking regulatory approval for digital mental health products.

Measurement of Adverse Events in Studies of Digital Health Interventions for Psychosis: Guidance and Recommendations Based on a Literature Search and Framework Analysis of Standard Operating Procedures.

BACKGROUND: Given the rapid expansion of research into digital health interventions (DHIs) for severe mental illness (SMI; eg, schizophrenia and other psychosis diagnoses), there is an emergent need for clear safety measures. Currently, measurement and reporting of adverse events (AEs) are inconsistent across studies. Therefore, an international network, iCharts, was assembled to systematically identify and refine a set of standard operating procedures (SOPs) for AE reporting in DHI studies for SMI. DESIGN: The iCharts network comprised experts on DHIs for SMI from seven countries (United Kingdom, Belgium, Germany, Pakistan, Australia, United States, and China) and various professional backgrounds. Following a literature search, SOPs of AEs were obtained from authors of relevant studies, and from grey literature. RESULTS: A thorough framework analysis of SOPs (n = 32) identified commonalities for best practice for certain domains, along with significant gaps in others; particularly around the classification of AEs during trials, and the provision of training/supervision for research staff in measuring and reporting AEs. Several areas which could lead to the observed inconsistencies in AE reporting and handling were also identified. CONCLUSIONS: The iCharts network developed best-practice guidelines and a practical resource for AE monitoring in DHI studies for psychosis, based on a systematic process which identified common features and evidence gaps. This work contributes to international efforts to standardize AE measurement and reporting in this emerging field, ensuring that safety aspects of DHIs for SMI are well-studied across the translational pathway, with monitoring systems set-up from the outset to support safe implementation in healthcare systems.

Adverse Events Reporting in Digital Interventions Evaluations for Psychosis: A Systematic Literature Search and Individual Level Content Analysis of Adverse Event Reports.

BACKGROUND: Digital health interventions (DHIs) have significant potential to upscale treatment access to people experiencing psychosis but raise questions around patient safety. Adverse event (AE) monitoring is used to identify, record, and manage safety issues in clinical trials, but little is known about the specific content and context contained within extant AE reports. This study aimed to assess current AE reporting in DHIs. STUDY DESIGN: A systematic literature search was conducted by the iCharts network (representing academic, clinical, and experts by experience) to identify trials of DHIs in psychosis. Authors were invited to share AE reports recorded in their trials. A content analysis was conducted on the shared reports. STUDY RESULTS: We identified 593 AE reports from 18 DHI evaluations, yielding 19 codes. Only 29 AEs (4.9% of total) were preidentified by those who shared AEs as being related to the intervention or trial procedures. While overall results support the safety of DHIs, DHIs were linked to mood problems and psychosis exacerbation in a few cases. Additionally, 27% of studies did not report information on relatedness for all or at least some AEs; 9.6% of AE reports were coded as unclear because it could not be determined what had happened to participants. CONCLUSIONS: The results support the safety of DHIs, but AEs must be routinely monitored and evaluated according to best practice. Individual-level analyses of AEs have merit to understand safety in this emerging field. Recommendations for best practice reporting in future studies are provided.

A targeted psychological treatment for sleep problems in young people at ultra-high risk of psychosis in England (SleepWell): a parallel group, single-blind, randomised controlled feasibility trial.

BACKGROUND: Sleep disturbance is common and problematic for young people at ultra-high risk of psychosis. Sleep disruption is a contributory causal factor in the occurrence of mental health problems, including psychotic experiences, anxiety, and depression. The implication is that treating sleep problems might have additional benefits on mental health outcomes in individuals at high risk. The present study had two aims: first, to establish the feasibility and acceptability of a randomised controlled trial to treat sleep problems with the aim of reducing psychotic experiences in young people at ultra-high risk of psychosis; and second, to provide proof of concept of the clinical efficacy of the treatment. METHODS: We did a parallel group, single-blind, randomised controlled feasibility trial in two National Health Service trusts in England. Eligible participants were aged 14-25 years, a patient of mental health services, assessed as being at ultra-high risk of psychosis on the Comprehensive Assessment of At-Risk Mental States, and having current sleep problems (score of ≥15 on the self-report Insomnia Severity Index [ISI]). Participants were randomly assigned (1:1) to either a targeted psychological therapy for sleep problems (SleepWell) plus usual care or usual care alone via an automated online system, with non-deterministic minimisation that balanced participants for ISI score and referring service. The SleepWell therapy was delivered on an individual basis in approximately eight 1-h sessions over 12 weeks. Assessments were done at 0, 3, and 9 months, with trial assessors masked to treatment allocation. The key feasibility outcomes were the numbers of patients identified, recruited, and retained, treatment uptake, and data completion. Treatment acceptability was measured with the Abbreviated Acceptability Rating Profile (AARP). In preliminary clinical assessments, the primary clinical outcome was insomnia at 3 and 9 months assessed with the ISI, reported by randomised group (intention-to-treat analysis). Safety was assessed in all randomly assigned participants. The trial was prospectively registered on ISRCTN, 85601537, and is completed. FINDINGS: From Nov 18, 2020, to Jan 26, 2022, 67 young people were screened, of whom 40 (60%) at ultra-high risk of psychosis were recruited. Mean age was 16·9 years (SD 2·5; range 14-23), and most participants identified as female (n=19 [48%]) or male (n=19 [48%]) and as White (n=32 [80%]). 21 participants were randomly assigned to SleepWell therapy plus usual care and 19 to usual care alone. All participants provided data on at least one follow-up visit. 39 (98%) of 40 participants completed the primary outcome assessment at 3 and 9 months. 20 (95%) of 21 participants assigned to SleepWell therapy received the prespecified minimum treatment dose of at least four sessions. The median treatment acceptability score on the AARP was 48 (IQR 46 to 48; n=17; maximum possible score 48). At the post-intervention follow-up (3 months), compared with the usual care alone group, the SleepWell therapy group had a reduction in insomnia severity (ISI adjusted mean difference -8·12 [95% CI -11·60 to -4·63]; Cohen's d=-2·67 [95% CI -3·81 to -1·52]), which was sustained at 9 months (ISI adjusted mean difference -5·83 [-9·31 to -2·35]; Cohen's d=-1·91 [-3·06 to -0·77]). Among the 40 participants, eight adverse events were reported in six participants (two [11%] participants in the usual care group and four [19%] participants in the SleepWell therapy group). One serious adverse event involving hospital admission for a physical health problem was reported in the SleepWell therapy group, and one patient in the usual care alone group transitioned to psychosis. None of these events were classed as being related to trial treatment or procedures. INTERPRETATION: A randomised controlled trial of a targeted psychological sleep therapy for young people at ultra-high risk of psychosis is feasible. Patients can be retained in the trial and assessments done by masked assessors. Uptake of the sleep therapy was high, and we found preliminary evidence of sustained reductions in sleep problems. A definitive multicentre trial is now needed. FUNDING: NIHR Research for Patient Benefit and NIHR Oxford Health Biomedical Research Centre.

A Safe Place to Learn: Peer Research Qualitative Investigation of gameChange Virtual Reality Therapy.

BACKGROUND: Automated virtual reality (VR) therapy has the potential to substantially increase access to evidence-based psychological treatments. The results of a multicenter randomized controlled trial showed that gameChange VR cognitive therapy reduces the agoraphobic avoidance of people diagnosed with psychosis, especially for those with severe avoidance. OBJECTIVE: We set out to use a peer research approach to explore participants' experiences with gameChange VR therapy. This in-depth experiential exploration of user experience may inform the implementation in clinical services and future VR therapy development. METHODS: Peer-led semistructured remote interviews were conducted with 20 people with a diagnosis of psychosis who had received gameChange as part of the clinical trial (ISRCTN17308399). Data were analyzed using interpretative phenomenological analysis and template analyses. A multiperspectival approach was taken to explore subgroups. Credibility checks were conducted with the study Lived Experience Advisory Panel. RESULTS: Participants reported the substantial impact of anxious avoidance on their lives before the VR intervention, leaving some of them housebound and isolated. Those who were struggling the most with agoraphobic avoidance expressed the most appreciation for, and gains from, the gameChange therapy. The VR scenarios provided "a place to practise." Immersion within the VR scenarios triggered anxiety, yet participants were able to observe this and respond in different ways than usual. The "security of knowing the VR scenarios are not real" created a safe place to learn about fears. The "balance of safety and anxiety" could be calibrated to the individual. The new learning made in VR was "taken into the real world" through practice and distilling key messages with support from the delivery staff member. CONCLUSIONS: Automated VR can provide a therapeutic simulation that allows people diagnosed with psychosis to learn and embed new ways of responding to the situations that challenge them. An important process in anxiety reduction is enabling the presentation of stimuli that induce the original anxious fears yet allow for learning of safety. In gameChange, the interaction of anxiety and safety could be calibrated to provide a safe place to learn about fears and build confidence. This navigation of therapeutic learning can be successfully managed by patients themselves in an automated therapy, with staff support, that provides users with personalized control. The clinical improvements for people with severe anxious avoidance, the positive experience of VR, and the maintenance of a sense of control are likely to facilitate implementation.

User-Centered Development of STOP (Successful Treatment for Paranoia): Material Development and Usability Testing for a Digital Therapeutic for Paranoia.

BACKGROUND: Paranoia is a highly debilitating mental health condition. One novel intervention for paranoia is cognitive bias modification for paranoia (CBM-pa). CBM-pa comes from a class of interventions that focus on manipulating interpretation bias. Here, we aimed to develop and evaluate new therapy content for CBM-pa for later use in a self-administered digital therapeutic for paranoia called STOP ("Successful Treatment of Paranoia"). OBJECTIVE: This study aimed to (1) take a user-centered approach with input from living experts, clinicians, and academics to create and evaluate paranoia-relevant item content to be used in STOP and (2) engage with living experts and the design team from a digital health care solutions company to cocreate and pilot-test the STOP mobile app prototype. METHODS: We invited 18 people with living or lived experiences of paranoia to create text exemplars of personal, everyday emotionally ambiguous scenarios that could provoke paranoid thoughts. Researchers then adapted 240 suitable exemplars into corresponding intervention items in the format commonly used for CBM training and created 240 control items for the purpose of testing STOP. Each item included newly developed, visually enriching graphics content to increase the engagement and realism of the basic text scenarios. All items were then evaluated for their paranoia severity and readability by living experts (n=8) and clinicians (n=7) and for their item length by the research team. Items were evenly distributed into six 40-item sessions based on these evaluations. Finalized items were presented in the STOP mobile app, which was co-designed with a digital health care solutions company, living or lived experts, and the academic team; user acceptance was evaluated across 2 pilot tests involving living or lived experts. RESULTS: All materials reached predefined acceptable thresholds on all rating criteria: paranoia severity (intervention items: ≥1; control items: ≤1, readability: ≥3, and length of the scenarios), and there was no systematic difference between the intervention and control group materials overall or between individual sessions within each group. For item graphics, we also found no systematic differences in users' ratings of complexity (P=.68), attractiveness (P=.15), and interest (P=.14) between intervention and control group materials. User acceptance testing of the mobile app found that it is easy to use and navigate, interactive, and helpful. CONCLUSIONS: Material development for any new digital therapeutic requires an iterative and rigorous process of testing involving multiple contributing groups. Appropriate user-centered development can create user-friendly mobile health apps, which may improve face validity and have a greater chance of being engaging and acceptable to the target end users.

Temporal trends in eating disorder and self-harm incidence rates among adolescents and young adults in the UK in the 2 years since onset of the COVID-19 pandemic: a population-based study.

BACKGROUND: Self-harm and eating disorders share multiple risk factors, with onset typically during adolescence or early adulthood. We aimed to examine the incidence rates of these psychopathologies among young people in the UK in the 2 years following onset of the COVID-19 pandemic. METHODS: We conducted a population-based study using the primary care electronic health records of patients aged 10-24 years in the UK Clinical Practice Research Datalink (CPRD). The observation period was from Jan 1, 2010, to March 31, 2022. We calculated the monthly incidence rates of eating disorders and self-harm according to the first record of each outcome. On the basis of antecedent trends between January, 2010, and February, 2020, negative binomial regression models were fitted to predict monthly incidence rates after the pandemic began in March, 2020. Percentage differences between observed and expected incidence were calculated to indicate changes since the onset of the pandemic, with stratification by sex, age, and deprivation quintile. FINDINGS: The primary care health records of 9 184 712 patients aged 10-24 years (4 836 226 [52·7%] female patients and 4 348 486 [47·3%] male patients; n=1881 general practices) were included for analysis. The incidence rates of eating disorders and self-harm among girls were higher than expected between March 1, 2020, and March 31, 2022. The observed incidence of eating disorders was 42·4% (95% CI 25·7-61·3) higher than expected for girls aged 13-16 years, and 32·0% (13·3-53·8) higher than expected for girls aged 17-19 years, whereas other age groups showed little difference between observed and expected incidence. Similarly, the increase in self-harm incidence was driven by girls aged 13-16 years, for whom the observed incidence was 38·4% (20·7-58·5) higher than expected. By contrast, among boys in all age groups, the incidence rates of eating disorders and self-harm were lower than, or close to, the expected rates. Among boys, the observed incidence of eating disorders was 22·8% (9·2-34·4) lower than expected, and the observed incidence of self-harm was 11·5% (3·6-18·7) lower than expected. The estimated increases in eating disorder and self-harm incidence among girls aged 13-16 years were largely attributable to increases within less deprived communities. INTERPRETATION: Although causes are uncertain, increased incidence of eating disorder diagnoses and self-harm among teenage girls in the UK during the first 2 years of the COVID-19 pandemic highlight an urgent need for intervention. Early identification of mental health difficulties by primary care clinicians is necessary. Timely access to treatments and sufficient support from general practitioners and mental health services needs to be available to manage presenting problems and to prevent exacerbations of conditions. FUNDING: National Institute for Health and Care Research.

Randomised controlled trial of automated VR therapy to improve positive self-beliefs and psychological well-being in young people diagnosed with psychosis: a study protocol for the Phoenix VR self-confidence therapy trial.

INTRODUCTION: The confidence of young people diagnosed with psychosis is often low. Positive self-beliefs may be few and negative self-beliefs many. A sense of defeat and failure is common. Young people often withdraw from many aspects of everyday life. Psychological well-being is lowered. Psychological techniques can improve self-confidence, but a shortage of therapists means that very few patients ever receive such help. Virtual reality (VR) offers a potential route out of this impasse. By including a virtual coach, treatment can be automated. As such, delivery of effective therapy is no longer reliant on the availability of therapists. With young people with lived experience, we have developed a staff-assisted automated VR therapy to improve positive self-beliefs (Phoenix). The treatment is based on established cognitive behavioural therapy and positive psychology techniques. A case series indicates that this approach may lead to large improvements in positive self-beliefs and psychological well-being. We now aim to conduct the first randomised controlled evaluation of Phoenix VR. METHODS AND ANALYSIS: 80 patients with psychosis, aged between 16 and 30 years old and with low levels of positive self-beliefs, will be recruited from National Health Service (NHS) secondary care services. They will be randomised (1:1) to the Phoenix VR self-confidence therapy added to treatment as usual or treatment as usual. Assessments will be conducted at 0, 6 (post-treatment) and 12 weeks by a researcher blind to allocation. The primary outcome is positive self-beliefs at 6 weeks rated with the Oxford Positive Self Scale. The secondary outcomes are psychiatric symptoms, activity levels and quality of life. All main analyses will be intention to treat. ETHICS AND DISSEMINATION: The trial has received ethical approval from the NHS Health Research Authority (22/LO/0273). A key output will be a high-quality VR treatment for patients to improve self-confidence and psychological well-being. TRIAL REGISTRATION NUMBER: ISRCTN10250113.