Combined intervention program of serious virtual reality games focused on controllability and Stress Inoculation Training in patients with major depression.

Introduction: Major depressive disorder (MDD) is a debilitating mental health condition with a high global prevalence, characterized by profound psychological and neurobiological alterations. Although many patients respond effectively to pharmacological and psychotherapeutic interventions, the persistently high rate of treatment resistance underscores the urgent need for novel strategies that target stress regulation and promote neuroplasticity. The aim of this study was determining the effect of a Virtual Reality Stress Inoculation Training (VR-SIT) in patients with MDD suffering mild and moderate episodes. In this experimental study, 54 patients diagnosed with MDD were randomly assigned to either the VR-SIT group or the Traditional Treatment (TT) group. Inclusion criteria included a diagnosis of MDD and a Hamilton Depression Scale score greater than 15. The TT group received standard pharmacological and psychotherapy treatment, while the VR-SIT group received pharmacological treatment combined with a virtual reality intervention. Depression severity and motivation were assessed using the Hamilton Depression Rating Scale (HAM-D) and a visual analog scale, respectively. Results: The mean age of participants was 26.26 years, with a mean disease duration of 9.93 months. Both groups exhibited a significant reduction in Hamilton Depression Scale scores from 18.15 pre-treatment to 10.33 post-treatment with no significant differences between groups. However, significant increases in motivation were observed in the VR-SIT group during Week 3 and at the end of the intervention, indicating higher motivation levels compared to the TT group. Conclusions: Both TT and VR-SIT interventions significantly reduced depressive symptoms; however, only VR-SIT was associated with a progressive and significantly greater increase in motivation. Future research should investigate long-term effects, elucidate the specific mechanisms underlying the controllability component, and standardize treatment protocols to enhance comparability and robustness.