Virtual reality-based cognitive remediation versus virtual reality control in people with mood or psychosis spectrum...

There is a paucity of real-life-like cognitive training programmes to bolster the transfer of treatment-related cognitive gains to daily-life functioning. We aimed to investigate the effects of 4-week, intensive virtual reality-based cognitive remediation therapy (VR-CRT) involving daily-life challenges versus an active virtual reality control treatment on cognition and functioning in patients with mood or psychosis spectrum disorders.

This was a single-centre, double-blind, parallel-group, randomised controlled trial at the Psychiatric Centre Copenhagen in Denmark. Clinically stable outpatients aged 18-55 years with an ICD-10 diagnosis of unipolar disorder, bipolar disorder, or a psychosis spectrum disorder, and with clinically relevant objective and subjective cognitive impairment were included. Participants were randomly assigned (1:1) to 4 weeks of VR-CRT or virtual reality control treatment and assessed at baseline, treatment completion (5 weeks) and follow-up (17 weeks). Randomisation used the REDCap module with block randomisation (block sizes four to eight), stratified by age (<35 vs ≥35 years) and diagnosis (mood disorder vs psychosis spectrum disorder), with allocation concealed from the enrolling author. The primary outcome was a global functional cognitive capacity score on the Cognition Assessment in Virtual Reality test at week 5. This trial was registered with ClinicalTrials.gov, NCT06038955, and is completed.

Between Oct 10, 2022, and Aug 9, 2024, 103 candidates were assessed for eligibility, of whom 62 participants were enrolled and randomly assigned (VR-CRT group n=31 and control group n=31). Of the 30 participants commencing VR-CRT, 28 (93%) completed treatment per protocol. At week 5, the mean Z score improvement in the global functional cognitive capacity score was 1·5 (SD 0·6) in the VR-CRT group and 0·4 (0·8) in the virtual reality control group (treatment effect 0·98 [95% CI 0·65-1·32]; p<0·0001; d=1·55). This effect was maintained at follow-up at week 17 (mean Z score improvement 1·6 [0·5] vs 0·6 [0·7]; treatment effect 0·91 [0·61-1·21]; p<0·0001; d=1·53). The intervention was well tolerated with no treatment-related serious adverse events.

Improvement in functional cognitive capacity was significantly greater in the VR-CRT group than the control group, and the intervention was well tolerated. Our findings suggest that embedding cognitive strategy training in immersive virtual reality can enhance transfer to real-world functioning, offering a feasible, engaging solution for cognitive rehabilitation in psychiatry.

TrygFonden, Axel Muusfeldts Foundation, Jascha Foundation, Ivan Nielsen Foundation, and Familien Hede Nielsen Foundation.