Automated psychological therapy using virtual reality (VR) for patients with persecutory delusions: study protocol for a single-blind parallel-group randomised controlled trial (THRIVE)

Persecutory delusions are a person’s unfounded beliefs that other people are intending to harm that person (e.g. ‘People know what I’m thinking and are trying to kill me’). Approximately 70% of patients with schizophrenia have this type of psychotic experience [1], which typically leads to social withdrawal, suicidal ideation, and hospital admission [2‐5]. Almost half of individuals with persecutory delusions have levels of psychological well-being in the lowest 2% of the general population [6]. However, more than half of patients with psychotic conditions such as schizophrenia do not respond adequately to current treatments [7, 8]. The median treatment effect size for antipsychotic medications is 0.44 [9], while standard first generation psychological therapy has an effect size of approximately 0.36 [10]. These are small to moderate effects for a patient group that has severe problems. Treatment needs to be significantly improved. We take a translational approach, allied to technological advances, for new treatment development for persecutory delusions.

Our cognitive model conceptualises persecutory delusions as unfounded threat beliefs maintained by defence (‘safety-seeking’) behaviours [11]. Patients, for example, often avoid other people, avert their gaze, and remain vigilant, attributing the absence of harm to the use of such actions instead of the inaccuracy of the threat beliefs (e.g. ‘The reason I wasn’t attacked was because I kept away from people’). The target mechanism for successful treatment is for patients to relearn that they are safe (in order to counteract the threat belief). This involves re-evaluating the threat beliefs. However, many patients with persecutory delusions find it too difficult to enter their feared situations and drop their defences because of the intolerable anxiety generated. When they are admitted to psychiatric hospital, opportunities for learning of safety in everyday situations are even more highly restricted.

We have argued that virtual reality ([VR] interactive computer-generated environments) may provide a powerful treatment approach for patients to enable the learning of safety that can reduce delusions [12, 13]. In a controlled environment with a graded approach, VR allows individuals to repeatedly experience the situations they find difficult and potentially enable new learning. Patients are much more likely to test out their fear expectations in VR because they know it is a simulation, but the learning that they achieve then transfers to the real world. VR treatments have the potential to be faster, more efficacious, and appealing to patients than traditional face-to-face approaches. Initially we showed that VR can be used to assess paranoia [14] and understand the causes [15], and that it is safe to use with patients with persecutory delusions [16]. We then conducted a first test of VR to treat persecutory delusions [17]. In this pilot study, 30 patients with persecutory delusions (despite taking antipsychotic medication) in the context of schizophrenia spectrum disorders were randomised to VR cognitive treatment (VRCT) (testing threat beliefs while dropping defence behaviours) or VR exposure therapy (VRET). We used 30 min in graded VR environments (a train and lift scenario) with psychological advice provided by a therapist. Before and after VR, the patients completed a real world situation task that they found difficult (e.g. going into a shop), and the delusion was assessed. In comparison to VRET, VRCT led to large reductions in delusions (d = 1.3) and in distress in the real world (d = 0.8). In sum, there were large improvements in delusions and a transfer of benefits to the real world, even compared to another effective treatment approach [17]. Recently, a randomised controlled trial of more than 100 patients with psychosis showed that 16 sessions with a therapist using VR also produced large reductions in paranoia compared to usual care (d = 1.5) [18].

Previous uses of VR for mental health problems have all used VR to elicit symptoms; a therapist then provides the psychological therapy [13]. Hence, VR has been used as an aid for therapists. However, we have recently shown that it is possible to automate the provision of psychological therapy with VR. We tested the efficacy of an automated cognitive intervention for fear of heights guided by an avatar virtual coach (animated using the motion and voice capture of an actor) in VR and delivered with the latest consumer equipment [19]. The effect sizes of the VR treatment were very large (Cohen’s d = 2.0; the number needed to treat [NNT] to reduce fear by at least 50% was 1.3). In our new trial (THRIVE) we will test a four-session automated cognitive treatment in VR (VRCT) for patients with persecutory delusions. This is part of a larger programme of work by our team — called ‘gameChange’ (www.​gameChangeVR.​com) — developing the use of VR for patients with psychosis.

VRCT comprises two key elements: (1) entering the feared situations and (2) not using defence (‘safety-seeking’) behaviours. By testing against exposure, our pilot actually controlled for the first treatment element of entering the feared situations. This means that the ‘in toto’ effect of the cognitive treatment will have been underestimated. We will now estimate treatment effects by comparing against a highly credible VR control treatment (mental relaxation training) that does not use either of the key cognitive elements. The primary hypothesis is that:

The secondary hypotheses are that:

The trial is called THRIVE (THerapeutic Realistic Immersive Virtual Environments). The design is a parallel-group randomised controlled trial with single-blind assessment to test whether the automated VRCT will reduce persecutory delusions more effectively than VR mental relaxation (VRMR). Standard care will be measured but remain as usual in both groups. Assessments will be carried out at 0, 2, 4 (post treatment), 8, 16, and 24 weeks by a researcher blind to treatment allocation (see Fig. 1 for the trial flow diagram). The repeated follow-up points are used to enable the observation of the time course of any treatment effects. The trial has received approvals from the National Health Service (NHS) Health Research Authority and a notice of no objection for a trial of a medical device from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), and it has been prospectively registered (ISRCTN12497310; http://​www.​isrctn.​com/​ISRCTN12497310). Written informed consent will be obtained from all trial participants. There is a trial Data Monitoring and Ethics Committee (DMEC). The trial is also supported by a Patient Advisory Group (PAG) run for our research group by the McPin Foundation. The basic trial methods of enrolment, interventions, and assessments are summarised in Fig. 2. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist is provided as Additional file 1.

Over the past 25 years VR has been applied with promising results to the understanding and treatment of mental health disorders. Its use in treatment has been as an aid for therapists, typically delivering exposure treatments; therefore, the potential clinical benefits of VR have still relied on the abilities of the clinician in the room. The THRIVE trial will provide a first test of an automated delivery of psychological therapy using VR for patients with psychosis. Therefore, patients can all experience the same standard of psychological therapy. The therapy delivered in VR is built upon the principle that paranoia diminishes when expectations of harm from other people are put to the test. The comparison in the trial is against similar time in VR but encouraging the reduction of fear via relaxation techniques (i.e. using a different psychological intervention and mechanism). There are repeated follow-up assessments of the main outcome to enable the persistence of any clinical gains to be tracked over time and in order to support mediation tests. The THRIVE trial also provides a first opportunity to learn lessons about the implementation of automated psychological therapy using consumer equipment within UK NHS mental health trusts. It will inform our new National Institute for Health Research (NIHR) i4i mental health challenge award programme of work, gameChange (www.​gameChangeVR.​com). In gameChange, the VR treatment has been completely redesigned, reprogrammed, lengthened, and made suitable for any patient with psychosis who is fearful of social situations. It will be tested in a large multi-centre trial starting later in 2019. The gameChange project also systematically examines implementation issues for automated VR treatment in psychosis services [36].