Cognitive rehabilitation with immersive virtual reality in schizophrenia: A randomized waiting list-controlled study
Background Cognitive symptoms represent a major determinant of long-term disability in chronic schizophrenia and only partially respond to pharmacotherapy. Evidence is growing about the potential effect of cognitive interventions to promote functional recovery. Immersive virtual reality (IVR) offers a simulated, adaptive, and ecologically valid real-world-like scenarios in safe and controlled environments. The present study aimed to evaluate the feasibility, acceptability, and efficacy of IVR-based cognitive rehabilitation in schizophrenia. Methods We performed a single-blind, randomized, waiting list (WL) controlled trial (Clinicaltrials.gov:NCT07427485). Forty clinically stable outpatients with schizophrenia were allocated (1:1) to IVR or WL. The intervention consisted of 12 weekly IVR-sessions through the CEREBRUM-VR tool. Primary outcome was the change in psychotic symptoms (Positive and Negative Symptoms Scale/PANSS). Secondary outcomes included global functioning (GAF), Digital Symbol Substitution Test (DSST), Animal Naming Test (ANT), Trail-Making Test A (TMT-A). Simple Reaction Choice (SRT) and Choice Reaction Time (CRT) evaluated psychomotor speed. Results Drop-out rate was 15% per group, attrition rate was 4.9%. Most IVR-assigned participants (77.8%) reported willingness to continue. IVR did not worsen overall or positive psychotic symptoms. A significant IVR between-group improvement emerged for negative symptoms (p < 0.01), psychomotor speed (SRT p = 0.01, CRT p = 0.01), DSST (p = 0.02), and ANT (p = 0.04). GAF and TMT-A changes were nonsignificant. Adverse effects were mostly mild and transient, decreasing over repeated sessions. Conclusion IVR-based cognitive rehabilitation appears feasible and tolerated in stable outpatients with schizophrenia. Our findings suggest improvement in psychomotor speed and modest improvement in negative symptoms. Larger and longer trials are warranted to confirm clinical relevance.