Seventy per cent of patients with schizophrenia and other psychotic disorders suffer from paranoid delusions, that are characterized by strong suspiciousness with the unfounded belief that other people are trying to harm them [
1]. Paranoid delusions are associated with great distress, anxiety, depression, suicidal thoughts, and hospital admission [
2,
3]. Furthermore, patients with paranoid delusions often experience problems in social functioning [
4]. To avoid perceived threat, i.e., the fear that others may deliberately cause them harm, patients withdraw from social interactions and crowded places. This complicates daily life, as regular activities such as seeing friends, talking to people, shopping, walking on the street or using public transport pose a major challenge. Many patients are socially isolated, have small social networks, and are unemployed [
5]. Since paranoid delusions and associated difficulties in social functioning cause a large burden on patients, effective interventions are of great importance. Main treatment options for schizophrenia and other psychotic disorders are antipsychotic medication and psychological treatment. A meta-analysis calculated a small to medium effect size of 0.44 for antipsychotic medication [
6]. Many patients discontinue their medication regime due to the serious side effects of antipsychotics. Cognitive-behavioural therapy for psychosis (CBTp) is the main evidence-based psychological treatment for paranoid delusions [
7]. CBTp for paranoid delusions aims to challenge delusional beliefs by means of cognitive restructuring and behavioural interventions such as exposure and experiments testing thoughts and beliefs. However, behavioural interventions are often too stressful for patients, as a result of which they avoid those interventions. Moreover, the meticulous preparation required preceding behavioural interventions is time-consuming for therapists, as a result of which this part of CBTp is often not properly performed in clinical practice [
8]. Although CBTp is the most effective psychological treatment for paranoid delusions, a recent meta-analysis reported only a small to medium effect size of 0.36 [
9]. Nearly half of the patients with schizophrenia and other psychotic disorders do not benefit from current treatments. Therefore, an improvement of treatment is urgently required. Virtual Reality (VR) has a great potential to improve psychological treatment of paranoid delusions. VR is the computer-generated simulation of a three-dimensional environment in which patients can interact with objects and virtual characters in a seemingly real or physical way using special electronic equipment, such as a helmet with a screen inside (head-mounted display, HMD). VR provides a powerful experience that can be used to help patients with paranoid delusions dealing with environments and social situations that make them paranoid or anxious [
10]. In a controlled environment with a therapist’s guidance, patients can practice gradually with personalized exposure exercises and behavioural experiments in social situations. VR allows patients to repeatedly experience difficult daily life situations and practice new behaviour with direct feedback from the therapist. Also, patients are aware of the option to withdraw from the VR environments at any time, which makes VR exposure safer and more accessible compared to exposure within CBTp. The interactive nature of VR enables provocation of emotions and responses similar to real environments [
11]. To summarize, VR provides an accessible, safe real-world experience in which patients can practice with difficulties in daily life while being coached by a therapist. Previous studies revealed emerging evidence of the potential to treat mental health problems with VR. In the treatment of patients with anxiety, VR has been proven effective and safe [
11,
12]. VR is also safe to use in the treatment of patients with a psychotic disorder, and emerging evidence suggests its effectiveness [
13]. A pilot study with thirty patients with psychosis reported a large effect size of 1.3 for a short VR based CBT (VRcbt) intervention targeting persecutory delusions, compared to virtual reality exposure [
14]. Our group recently conducted the first randomized controlled trial (RCT) of VRcbt with 116 patients and showed that, compared to waiting list, VRcbt is effective for reducing paranoia (d = 1.6) and anxiety (d = 0.7) in patients with schizophrenia and related psychotic disorders [
15]. Additionally, significant improvements were established for ideas of persecution, ideas of social reference, and use of safety behaviours. An advantage of VR, highly valued by both patients and therapists, was the possibility to start exposure immediately and successfully.
Moreover, VRcbt has the potential to improve mental health more cost-effectively. A recent meta-analysis of CBTp showed that patients with paranoid delusions are more likely to benefit from treatment when a higher number of CBTp sessions are offered [
16], making CBTp time-consuming and expensive. Furthermore, the availability of CBTp is limited for patients with a psychotic disorder. Less than 10% of patients with psychosis are offered CBTp [
17,
18]. Meanwhile, first evidence indicates that VRcbt has the potential to achieve positive results in fewer sessions compared to CBTp [
14]. In our previous RCT, we aimed to get an impression of the short-term cost-effectiveness of VRcbt for patients with paranoid delusions compared to TAU, from a societal perspective. The VRcbt treatment condition was more expensive than TAU alone, which was to be expected, as VRcbt was added to regular treatment. The incremental cost-effectiveness ratio (ICER) per quality adjusted life year (QALY) gained, however, was within acceptable limits, as was the ICER for other relevant outcomes. At three month follow-up, the VRcbt group had lower health care costs and reduced costs due to productivity loss compared to the TAU alone group. Moreover, there were no psychiatric admission days for the VRcbt group at follow-up. To summarize, these results indicate acceptable cost-effectiveness of VRcbt, even in comparison to a waiting-list control condition without extra costs. In the current study, we take a next step by investigating effectiveness and cost-effectiveness of VRcbt by comparing VRcbt directly to CBTp.