Virtual reality supported therapy for the negative symptoms of schizophrenia: the V-NeST feasibility RCT
Authors: Cella Matteo , Tomlin Paul , Robotham Daniel , Green Patrick , Griffiths Helena , Stahl Daniel , Valmaggia Lucia 
Published: October 2023

Background
Negative symptoms are typically observed in people with schizophrenia and indicate a loss or reduction of a normal function (e.g. reduced motivation and affect display). Despite obstructing people’s recovery, intervention development receives limited attention.

Objectives
This study evaluates, for the first time, the feasibility and acceptability of a novel Virtual Reality Supported Therapy for the Negative SympToms of Psychosis.

Design
This is a single (rater)-blind randomised study with two conditions (Virtual Reality Supported Therapy for the Negative SympToms of Psychosis plus treatment as usual vs. treatment as usual alone) recruiting people with schizophrenia experiencing debilitating negative symptoms. Assessments are at baseline and at 3-month postrandomisation.

Setting
Psychosis outpatient clinics.

Main outcome measures
The prespecified primary outcome is participants’ goal attainment, and secondary outcomes are negative symptoms and functioning. The study assesses feasibility and acceptability parameters including recruitment, eligibility, treatment adherence and retention. Acceptability is evaluated qualitatively using a post-therapy feedback interview and data analysed through thematic analysis. Therapy effect on outcomes is estimated using intention-to-treat principles.

Results
The study recruited its prespecified target of 30 participants (15 randomised to Virtual Reality Supported Therapy for the Negative SympToms of Psychosis). Two participants in each therapy arm were either ‘lost at follow-up’ or discontinued the trial. Therapy engagement for those randomised to Virtual Reality Supported Therapy for the Negative SympToms of Psychosis was appropriate and research procedures were considered feasible. Nine participants took part in the acceptability interview and described the therapy and virtual reality procedures as positive and useful. There were 2 serious adverse events for participants randomised to treatment as usual and 11 adverse events (7 in the Virtual Reality Supported Therapy for the Negative SympToms of Psychosis group and 4 in the treatment-as-usual group). Adverse events were not related to research and therapy procedures. Preliminary analysis suggested the therapy may have a large effect on participants’ goals and a possible effect on negative symptoms.

Limitations
The study was not able to evaluate the hypothesised mechanistic aspect of the therapy (i.e. reward learning) due to pandemic-imposed social distancing measures. The current study also did not have a follow-up assessment, and this limitation did not allow to assess possible change in intervention effect over time.

Conclusion
We showed that Virtual Reality Supported Therapy for the Negative SympToms of Psychosis is a feasible, acceptable and safe intervention. This therapy has the potential to support people with schizophrenia in achieving their recovery goals by reducing the burden of negative symptoms. The results of this study support further evaluation of Virtual Reality Supported Therapy for the Negative SympToms of Psychosis to assess its efficacy in an appropriately powered randomised controlled trial.

Study registration
The study protocol was pre-registered on ClinicalTrials.gov (identifier: NCT03995420).

Funding
This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership (NIHR-EME: 17/59/13). This will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 6. See the NIHR Journals Library website for further project information.