RecoVRy - a Randomized Controlled Trial Examining the Effect of Artificial Intelligence Powered Virtual Reality Treatment in Psychosis

Introduction Virtual Reality (VR) immerses people in digitally simulated environments that can provide exciting interactive experiences and is thus well established in the entertainment industry. VR is however not just about fun and games; therapeutic use of VR is becoming increasingly popular for a broad range of mental health conditions such as anxiety disorders, PTSD, phobias and chronic pain. Although the concept of VR as a treatment modality has gained momentum and (better) use of technology is an explicitly stated goal in health care strategies and guidelines, the use of VR therapy in severe mental illness is much less developed and has received less attention. The important question therefore arises whether VR therapy actually improves clinical and functional outcome in psychosis and whether it is cost-effective. The RecoVRy study will answer these questions in the first randomized controlled trial (RCT) combining virtual reality with state-of-the-art Artificial Intelligence (AI). A strong multidisciplinary team of researchers and clinicians (psychiatry, clinical psychology, health economy, digital health, and occupational therapy) will run this RCT in close collaboration with a world-renowned expert on VR therapy in psychosis.

Schizophrenia and psychotic disorders Psychotic disorders are rare, with a lifetime prevalence close to 1 %. Still, they impose a major burden of illness in terms of both individual suffering and societal cost. They are severe and often chronic mental disorders characterized by a heterogenic set of positive and negative psychotic symptoms, neurocognitive impairment, and functional decline. Total costs associated with schizophrenia spectrum disorders in Norway are estimated to approximately 10.2 billion NOK per year making it the 5th most expensive health condition, with indirect cost due to productivity loss accounting for as much as 30 % and only between 5 % - 10 % having paid employment. Despite increased etiological understanding and refined treatment approaches, today's standard psychosis treatment does not prevent a large proportion of individuals with schizophrenia becoming isolated and inactive, which in turn negatively affects both physical and mental health. Individuals with schizophrenia are estimated to lose 13 - 15 years of potential life years. Reduced quality of life, social withdrawal and inactivity may largely be explained by avoidance due to symptoms of anxiety. As many as two-thirds of patients with schizophrenia have levels of anxious avoidance equivalent to those in individuals with agoraphobia. Symptoms of anxiety emerge for different reasons; hallucinations, fear of rejection, harm or social humiliation, paranoia, social inexperience, and risk of stigma, and may contribute significantly to the functional impairment observed in schizophrenia. Alleviating anxiety symptoms may thus be key to help improve functional outcomes and tackle the serious issues of social withdrawal and inactivity in individuals with schizophrenia.

Whilst the effect of antipsychotic medication in reducing positive psychotic symptoms and risk of relapse is well-documented, non-response and poor adherence to antipsychotic medication is frequent. Furthermore, negative symptoms are often associated with a limited response to pharmacotherapy. Cognitive Behavioral Therapy for psychosis (CBTp) is an established psychotherapeutic intervention recommended in several international and national guidelines. Meta-analyses have reported small effects of CBTp on psychotic symptoms, and there is considerable room for improvement. It has been suggested that an increased focus on the behavioral component of CBT, using repeated behavioral experiments, behavioral activation and exposure, may increase the effect of CBTp. Virtual Reality facilitates exactly that; a greater focus on behavioural aspects of CBTp.

System-level factors also challenge the delivery of appropriate psychological treatments such as CBTp. Mental health services worldwide are faced with increased patient contact volume and clinician caseload size. Implementing CBTp requires resources often not present in the mental health system. It warrants therapists' education, a certain training volume, adherence to treatment and above all exposure and learning in real-world situations. Typically, clinicians have little to no time to accompany patients in sessions outside the clinic. This imbalance between demand and supply of mental health services underlines the need for an intervention directly addressing these issues, such as the RecoVRy study to bridge this gap.

Virtual Reality Exposure Therapy (VRET) VRET is a promising approach to ensure high-quality therapy and possibly increase effects - optimizing the therapist's time in a mental health system with limited resources. VRET utilizes modern technology to enable a more refined approach to exposure therapy, also within the context of CBTp. VR refers to a computer-generated environment with different scenes and objects that appear real, making the user feel that they are immersed in and can interact with their surroundings. In a clinical setting, therapist and client may use VRET to address difficult and complex situations in a highly controlled environment, in real time, eliciting responses equivalent to those in a real situation. The objective is to habituate learned fear responses or disprove catastrophic beliefs held by the client. VR provides ample opportunity to repeatedly challenge fears and beliefs first-hand, instead of addressing them through conversation in a classic therapeutic setting (later). VRET has been found to be a well-tolerated, safe treatment method without adverse effects in individuals with psychosis. Studies examining the effect of VR therapy on social skills and VR augmented CBT in individuals with social anxiety and paranoid thoughts indicate higher motivational levels, symptom and social skills improvements and reduced social avoidance. Combined with CBT, VR also reduced social anxiety and paranoia. Another potential benefit of VRET in psychosis treatment is the possibility of easing patients into situations they would otherwise find too frightening and consequently avoid In the large UK based RCT gameChange, VR therapy led to significant reductions in distress and anxious avoidance in and of real-world situations in patients with psychosis.